Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates the killing activity against Candida albicans.

PubMed

Bolscher, Jan; Nazmi, Kamran; van Marle, Jan; van 't Hof, Wim; Veerman, Enno

2012-06-01

Bovine lactoferrin harbors 2 antimicrobial sequences (LFcin and LFampin), situated in close proximity in the N1-domain. To mimic their semi parallel configuration we have synthesized a chimeric peptide (LFchimera) in which these sequences are linked in a head-to-head fashion to the α- and ε-amino group, respectively, of a single lysine. In line with previously described bactericidal effects, this peptide was also a stronger candidacidal agent than the antimicrobial peptides LFcin17-30 and LFampin265-284, or a combination of these 2. Conditions that strongly reduced the candidacidal activities of LFcin17-30 and LFampin265-284, such as high ionic strength and energy depletion, had little influence on the activity of LFchimera. Freeze-fracture electron microscopy showed that LFchimera severely affected the membrane morphology, resulting in disintegration of the membrane bilayer and in an efflux of small and high molecular weight molecules such as ATP and proteins. The differential effects displayed by the chimeric peptide and a mixture of its constituent peptides clearly demonstrate the synergistic effect of linking these peptides in a fashion that allows a similar spatial arrangement as in the parent protein, suggesting that in bovine lactoferrrin the corresponding fragments act in concert in its candidacidal activity.

Meditation leads to reduced default mode network activity beyond an active task.

PubMed

Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

2015-09-01

Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

Chandra and ALMA observations of the nuclear activity in two strongly lensed star-forming galaxies

NASA Astrophysics Data System (ADS)

Massardi, M.; Enia, A. F. M.; Negrello, M.; Mancuso, C.; Lapi, A.; Vignali, C.; Gilli, R.; Burkutean, S.; Danese, L.; Zotti, G. De

2018-02-01

Aim. According to coevolutionary scenarios, nuclear activity and star formation play relevant roles in the early stages of galaxy formation. We aim at identifying them in high-redshift galaxies by exploiting high-resolution and high-sensitivity X-ray and millimeter-wavelength data to confirm the presence or absence of star formation and nuclear activity and describe their relative roles in shaping the spectral energy distributions and in contributing to the energy budgets of the galaxies. Methods: We present the data, model, and analysis in the X-ray and millimeter (mm) bands for two strongly lensed galaxies, SDP.9 (HATLAS J090740.0-004200) and SDP.11 (HATLAS J091043.1-000322), which we selected in the Herschel-ATLAS catalogs for their excess emission in the mid-IR regime at redshift ≳1.5. This emission suggests nuclear activity in the early stages of galaxy formation. We observed both of them with Chandra ACIS-S in the X-ray regime and analyzed the high-resolution mm data that are available in the ALMA Science Archive for SDP.9. By combining the information available in mm, optical, and X-ray bands, we reconstructed the source morphology. Results: Both targets were detected in the X-ray, which strongly indicates highly obscured nuclear activity. ALMA observations for SDP.9 for the continuum and CO(6-5) spectral line with high resolution (0.02 arcsec corresponding to 65 pc at the distance of the galaxy) allowed us to estimate the lensed galaxy redshift to a better accuracy than pre-ALMA estimates (1.5753 ± 0.0003) and to model the emission of the optical, millimetric, and X-ray band for this galaxy. We demonstrate that the X-ray emission is generated in the nuclear environment, which strongly supports that this object has nuclear activity. On the basis of the X-ray data, we attempt an estimate of the black hole properties in these galaxies. Conclusions: By taking advantage of the lensing magnification, we identify weak nuclear activity associated with high

Digestion of chrysanthemum stunt viroid by leaf extracts of Capsicum chinense indicates strong RNA-digesting activity.

PubMed

Iraklis, Boubourakas; Kanda, Hiroko; Nabeshima, Tomoyuki; Onda, Mayu; Ota, Nao; Koeda, Sota; Hosokawa, Munetaka

2016-08-01

CSVd could not infect Nicotiana benthamiana when the plants were pretreated with crude leaf extract of Capsicum chinense 'Sy-2'. C. chinense leaves were revealed to contain strong RNA-digesting activity. Several studies have identified active antiviral and antiviroid agents in plants. Capsicum plants are known to contain antiviral agents, but the mechanism of their activity has not been determined. We aimed to elucidate the mechanism of Capsicum extract's antiviroid activity. Chrysanthemum stunt viroid (CSVd) was inoculated into Nicotiana benthamiana plants before or after treating the plants with a leaf extract of Capsicum chinense 'Sy-2'. CSVd infection was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) 3 weeks after inoculation. When Capsicum extract was sprayed or painted onto N. benthamiana before inoculation, it was effective in preventing infection by CSVd. To evaluate CSVd digestion activity in leaf extracts, CSVd was mixed with leaf extracts of Mirabilis, Phytolacca, Pelargonium and Capsicum. CSVd-digesting activities were examined by quantifying undigested CSVd using qRT-PCR, and RNA gel blotting permitted visualization of the digested CSVd. Only Capsicum leaf extract digested CSVd, and in the Capsicum treatment, small digested CSVd products were detected by RNA gel blot analysis. When the digesting experiment was performed for various cultivars and species of Capsicum, only cultivars of C. chinense showed strong CSVd-digesting activity. Our observations indicated that Capsicum extract contains strong RNA-digesting activity, leading to the conclusion that this activity is the main mechanism for protection from infection by CSVd through spraying or painting before inoculation. To our knowledge, this is the first report of a strong RNA-digesting activity by a plant extract.

Strong Broadband Terahertz Optical Activity through Control of the Blaschke Phase with Chiral Metasurfaces

NASA Astrophysics Data System (ADS)

Cole, Michael A.; Chen, Wen-chen; Liu, Mingkai; Kruk, Sergey S.; Padilla, Willie J.; Shadrivov, Ilya V.; Powell, David A.

2017-07-01

We demonstrate terahertz chiral metamaterials that achieve resonant transmission and strong optical activity. This response is realized in a metasurface coupled to its Babinet complement, with additional twist. Uniquely, the optical activity achieved in this type of metamaterial is weakly dispersive around the resonant transmission maxima, but it can be highly dispersive around the transmission minima. It has recently been shown that this unique optical activity response is closely related to zeros in the transmission spectra of circular polarizations through the Kramers-Kronig relations and strong resonant features in the optical activity spectrum corresponding to the Blaschke phase terms. Here we demonstrate how modifying the meta-atom geometry greatly affects the location and magnitude of these Blaschke phase terms. We study three different meta-atoms, which are variations on the simple cross structure. Their responses are measured using terahertz time-domain spectroscopy and analyzed via numerical simulations.

Recreational Activities to Reduce Behavioural Symptoms in Dementia

PubMed Central

Kolanowski, Ann; Fick, Donna M.; Buettner, Linda

2009-01-01

Few clinicians have an educational grounding in the use of nonpharmacological therapies for people with dementia. In this article, we explore the utility of recreational activities as one nonpharmacological intervention that has demonstrated effectiveness for reducing the behavioural symptoms of dementia. The implementation of effective recreational activities involves three components: understanding the evidence for this approach; acknowledging the need to reduce medications that have the potential to interfere with activity effectiveness; and individualizing activities so that the maximum benefit from the intervention is obtained. PMID:20046903

Permafrost thaw strongly reduces allowable CO2 emissions for 1.5°C and 2°C

NASA Astrophysics Data System (ADS)

Kechiar, M.; Gasser, T.; Kleinen, T.; Ciais, P.; Huang, Y.; Burke, E.; Obersteiner, M.

2017-12-01

We quantify how the inclusion of carbon emission from permafrost thaw impacts the budgets of allowable anthropogenic CO2 emissions. We use the compact Earth system model OSCAR v2.2 which we expand with a permafrost module calibrated to emulate the behavior of the complex models JSBACH, ORCHIDEE and JULES. When using the "exceedance" method and with permafrost thaw turned off, we find budgets very close to the CMIP5 models' estimates reported by IPCC. With permafrost thaw turned on, the total budgets are reduced by 3-4%. This corresponds to a 33-45% reduction of the remaining budget for 1.5°C, and a 9-13% reduction for 2°C. When using the "avoidance" method, however, permafrost thaw reduces the total budget by 3-7%, which corresponds to reductions by 33-56% and 56-79% of the remaining budget for 1.5°C and 2°C, respectively. The avoidance method relies on many scenarios that actually peak below the target whereas the exceedance method overlooks the carbon emitted by thawed permafrost after the temperature target is reached, which explains the difference. If we use only the subset of scenarios in which there is no net negative emissions, the permafrost-induced reduction in total budgets rises to 6-15%. Permafrost thaw therefore makes the emission budgets strongly path-dependent. We also estimate budgets of needed carbon capture in scenarios overshooting the temperature targets. Permafrost thaw strongly increases these capture budgets: in the case of a 1.5°C target overshot by 0.5°C, which is in line with the Paris agreement, about 30% more carbon must be captured. Our conclusions are threefold. First, inclusion of permafrost thaw systematically reduces the emission budgets, and very strongly so if the temperature target is overshot. Second, the exceedance method, that is the only one that complex models can follow, only partially accounts for the effect of slow non-linear processes such as permafrost thaw, leading to overestimated budgets. Third, the newfound

XPS analysis of activated carbon supported ionic liquids: Enhanced purity and reduced charging

NASA Astrophysics Data System (ADS)

Foelske-Schmitz, A.; Weingarth, D.; Kötz, R.

2011-12-01

Herein we report on XPS measurements on five different [EMIM] based ionic liquids (IL) prepared on activated carbon and aluminium supports. The anions were [TFSI], [BF4], [FAP], [B(CN)4] and [EtOSO3]. The results show that impurities such as O, Si or hydrocarbons were significantly reduced or no longer detected when preparation was performed on the high surface area carbon support. All core level spectra were fitted and for [EMIM][FAP], [EMIM][B(CN)4] and [EMIM][EtOSO3] de-convolution procedures of the C 1s lines are suggested. Comparison of the determined binding energies with published data strongly suggests that sample charging is irrelevant when preparation is performed on the activated carbon support. This observation is supposed to refer to the high capacitance of the high surface area carbon.

Biofabrication of polyphenols stabilized reduced graphene oxide and its anti-tuberculosis activity.

PubMed

Han, Wei; Niu, Wen-Yi; Sun, Bing; Shi, Guang-Can; Cui, Xiu-Qin

2016-12-01

A facile one step eco-friendly method for the reduction graphene oxide by Cinnamomumverum (C. verum) bark extract is reported in this work. This approach avoids the utilization of hazardous chemical reagents. The characterization results of various spectroscopic and microscopic techniques for the prepared graphene oxide (GO) and reduced graphene oxide (RGO) afford a strong indication of the removal of oxygen functionalities of GO after reduction and following stabilization by the oxidised polyphenols. Fourier transform infrared spectral results showed the capping of oxidised polyphenols onto the surface of reduced graphene oxide which further prevent their aggregation. Additionally, the prepared graphene nanosheets were tested for their antituberculosis activity against standard strain such as M. tuberculosis H37Ra. The obtained results suggested that the synthesized graphene acts as an effective growth inhibitors against M. tuberculosis H37Ra making it applicable for targeted drug delivery by combining with other chemical drugs as a therapeutic index. Copyright © 2016 Elsevier B.V. All rights reserved.

Hemin-utilizing G-quadruplex DNAzymes are strongly active in organic co-solvents.

PubMed

Canale, Thomas D; Sen, Dipankar

2017-05-01

The widespread use of organic solvents in industrial processes has focused in recent years on the utility of "green" solvents - those with less harmful environmental, health, and safety properties - such as methanol and formamide. However, protein enzymes, regarded as green catalysts, are often incompatible with organic solvents. Herein, we have explored the oxidative properties of a Fe(III)-heme, or hemin, utilizing catalytic DNA (heme·DNAzyme) in different green solvent-water mixtures. We find that the peroxidase and peroxygenase activities of the heme·DNAzyme are strongly enhanced in 20-30% v/v methanol or formamide, relative to water alone. Protic solvent content of >30% v/v gradually diminishes heme·DNAzyme catalytic activity; however, the heme·DNAzyme is still active in as high as 80% v/v methanol. In contrast to protic solvents, aqueous dimethylformamide solutions largely inhibit heme·DNAzyme activity. In view of the strong catalytic activity of heme·DNAzyme in aqueous methanol, we were able to determine that a 60% v/v methanol-water mixture gives the most optimal yield of the dibenzothiophene sulfoxide (DBTO) oxidation product of petroleum-derived dibenzothiophene (DBT). The high product yield reflects both DNAzyme catalysis and a high substrate availability. Overall, these results emphasize the excellent promise of G-quadruplex forming DNA catalysts in application to "greener" industrial chemistry. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

Symmetrical choline-derived dications display strong anti-kinetoplastid activity

PubMed Central

Ibrahim, Hasan M. S.; Al-Salabi, Mohammed I.; El Sabbagh, Nasser; Quashie, Neils B.; Alkhaldi, Abdulsalam A. M.; Escale, Roger; Smith, Terry K.; Vial, Henri J.; de Koning, Harry P.

2011-01-01

Objectives To investigate the anti-kinetoplastid activity of choline-derived analogues with previously reported antimalarial efficacy. Methods From an existing choline analogue library, seven antimalarial compounds, representative of the first-, second- and third-generation analogues previously developed, were assessed for activity against Trypanosoma and Leishmania spp. Using a variety of techniques, the effects of choline analogue exposure on the parasites were documented and a preliminary investigation of their mode of action was performed. Results The activities of choline-derived compounds against Trypanosoma brucei and Leishmania mexicana were determined. The compounds displayed promising anti-kinetoplastid activity, particularly against T. brucei, to which 4/7 displayed submicromolar EC50 values for the wild-type strain. Low micromolar concentrations of most compounds cleared trypanosome cultures within 24–48 h. The compounds inhibit a choline transporter in Leishmania, but their entry may not depend only on this carrier; T. b. brucei lacks a choline carrier and the mode of uptake remains unclear. The compounds had no effect on the overall lipid composition of the cells, cell cycle progression or cyclic adenosine monophosphate production or short-term effects on intracellular calcium levels. However, several of the compounds, displayed pronounced effects on the mitochondrial membrane potential; this action was not associated with production of reactive oxygen species but rather with a slow rise of intracellular calcium levels and DNA fragmentation. Conclusions The choline analogues displayed strong activity against kinetoplastid parasites, particularly against T. b. brucei. In contrast to their antimalarial activity, they did not act on trypanosomes by disrupting choline salvage or phospholipid metabolism, instead disrupting mitochondrial function, leading to chromosomal fragmentation. PMID:21078603

Strong fascin expression promotes metastasis independent of its F-actin bundling activity.

PubMed

Heinz, Lisa S; Muhs, Stefanie; Schiewek, Johanna; Grüb, Saskia; Nalaskowski, Marcus; Lin, Yuan-Na; Wikman, Harriet; Oliveira-Ferrer, Leticia; Lange, Tobias; Wellbrock, Jasmin; Konietzny, Anja; Mikhaylova, Marina; Windhorst, Sabine

2017-12-15

High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice. In addition, the effect of fascin mutants with inactive or constitutively active actin bundling activity was examined. Unexpectedly, we found that hyperexpression of both, wildtype (wt) and mutant fascin strongly increased metastasis in vivo , showing that the effect of fascin hyperexpression did not depend on its actin bundling activity. Cellular assays revealed that hyperexpression of wt and mutant fascin increased adhesion of MDA-MB-231 cells while transmigration and proliferation were not affected. Since it has been shown that fascin controls adhesion by directly interacting with microtubules ( MTs), we analyzed if fascin hyperexpression affects MT dynamics. We found that at high concentrations fascin significantly increased MT dynamics in cells and in cell-free approaches. In summary our data show that strong expression of fascin in breast cancer cells increases metastasis independent of its actin bundling activity. Thus, it seems that the mechanism of fascin-stimulated metastasis depends on its concentration.

Nacre-inspired integrated strong and tough reduced graphene oxide-poly(acrylic acid) nanocomposites

NASA Astrophysics Data System (ADS)

Wan, Sijie; Hu, Han; Peng, Jingsong; Li, Yuchen; Fan, Yuzun; Jiang, Lei; Cheng, Qunfeng

2016-03-01

Inspired by the relationship between interface interactions and the high performance mechanical properties of nacre, a strong and tough nacre-inspired nanocomposite was demonstrated based on graphene oxide (GO) and polyacrylic acid (PAA) prepared via a vacuum-assisted filtration self-assembly process. The abundant hydrogen bonding between GO and PAA results in both high strength and toughness of the bioinspired nanocomposites, which are 2 and 3.3 times higher than that of pure reduced GO film, respectively. In addition, the effect of environmental relative humidity on the mechanical properties of bioinspired nanocomposites is also investigated, and is consistent with previous theoretical predictions. Moreover, this nacre-inspired nanocomposite also displays high electrical conductivity of 108.9 S cm-1. These excellent physical properties allow this type of nacre-inspired nanocomposite to be used in many applications, such as flexible electrodes, aerospace applications, and artificial muscles etc. This nacre-inspired strategy also opens an avenue for constructing integrated high performance graphene-based nanocomposites in the near future.

Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.

PubMed

Hasegawa, Emi; Maejima, Takashi; Yoshida, Takayuki; Masseck, Olivia A; Herlitze, Stefan; Yoshioka, Mitsuhiro; Sakurai, Takeshi; Mieda, Michihiro

2017-04-25

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.

Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity

PubMed Central

Hasegawa, Emi; Maejima, Takashi; Yoshida, Takayuki; Herlitze, Stefan; Yoshioka, Mitsuhiro; Sakurai, Takeshi; Mieda, Michihiro

2017-01-01

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing. PMID:28396432

Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5

PubMed Central

Liu, Fulu; Kunter, Ghada; Krem, Maxwell M.; Eades, William C.; Cain, Jennifer A.; Tomasson, Michael H.; Hennighausen, Lothar; Link, Daniel C.

2008-01-01

A fundamental property of leukemic stem cells is clonal dominance of the bone marrow microenvironment. Truncation mutations of CSF3R, which encodes the G-CSF receptor (G-CSFR), are implicated in leukemic progression in patients with severe congenital neutropenia. Here we show that expression of a truncated mutant Csf3r in mice confers a strong clonal advantage at the HSC level that is dependent upon exogenous G-CSF. G-CSF–induced proliferation, phosphorylation of Stat5, and transcription of Stat5 target genes were increased in HSCs isolated from mice expressing the mutant Csf3r. Conversely, the proliferative advantage conferred by the mutant Csf3r was abrogated in myeloid progenitors lacking both Stat5A and Stat5B, and HSC function was reduced in mice expressing a truncated mutant Csf3r engineered to have impaired Stat5 activation. These data indicate that in mice, inappropriate Stat5 activation plays a key role in establishing clonal dominance by stem cells expressing mutant Csf3r. PMID:18292815

Large plasmaspheric electric fields at L approximately 2 measured by the S3-3 satellite during strong geomagnetic activity

NASA Technical Reports Server (NTRS)

Gonzalez, W. D.; Pinto, O., Jr.; Mendes, O., Jr.; Mozer, F. S.

1986-01-01

Large plasmaspheric electric fields at L is approximately 2 measured by the S3-3 satellite during strong geomagnetic activity are reported. Since these measurements have amplitudes comparable to those of the local corotation electric field, during such events the plasmasphere is expected to get strongly altered event at such low L-values. Furthermore, those measurements could contribute to the understanding of the physics of the convection/electric field penetration to the low latitude plasmaphere as well as the disturbed dynamo, during strong geomagnetic activity. For this purpose, critical parameters related to geomagnetic activity are also presented for the reported electric field events.

Reducing Skin Picking via Competing Activities

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Thompson, Ada; Reske, Cara L.; Gable, Lauren M.; Barton-Arwood, Sally

2006-01-01

This study examined the outcomes of a competing activities intervention to decrease skin picking exhibited by a 9-year-old student with comorbid diagnoses. Results of an ABCBAB design revealed that the use of student-selected manipulatives resulted in reduced skin picking. (Contains 1 figure.)

Solvothermal fabrication and enhanced visible light photocatalytic activity of Cu2O-reduced graphene oxide composite microspheres for photodegradation of Rhodamine B

NASA Astrophysics Data System (ADS)

Sun, Lingling; Wang, Guohong; Hao, Ruirui; Han, Deyan; Cao, Sheng

2015-12-01

The addition of graphene oxide (GO) in the semiconductors has been regarded as one of the effective methods to enhance their photocatalytic activity. In this study, Cu2O-reduced graphene oxide (Cu2O-rGO) composites with low loading (0-0.5 wt.%) of graphene oxide (GO) were produced by a one-step green solvothermal method in ethanol system by using Cu(NO3)2·3H2O and glutamic acid as copper precursor and reducing agent, respectively. During the solvothermal treatment, GO was reduced to rGO. The as-prepared Cu2O-reduced graphene oxide composite microspheres exhibited enhanced photocatalytic activity toward the degradation of RhB aqueous solution under visible light irradiation. At the optimal loading of graphene oxide (0.05 wt.%), Cu2O-rGO composites showed the highest photocatalytic activity, exceeding that of pure Cu2O and commercial Degussa P25 by a factor of 2.9 and 7.9, respectively. The enhanced photocatalytic activity may be ascribed to the strong coupling interaction between Cu2O particles and rGO nanosheets, which reduces the recombination of charge carriers.

Strong Effects of a Shelfbreak Jet on Microbial Enzyme Activities

NASA Astrophysics Data System (ADS)

Hoarfrost, A.; Balmonte, J. P.; Ziervogel, K.; Ghobrial, S.; Gawarkiewicz, G.; Arnosti, C.

2016-02-01

The activities of extracellular enzymes are critical in initiating microbial cycling of organic carbon, yet the dynamics of heterotrophic enzyme activities in marine environments are still poorly understood. Variations at a given site in rates of activity and the spectrum of organic substrates hydrolyzed may depend upon environmental context. We measured the extracellular enzymatic hydrolysis of 13 high- and low-molecular-weight organic substrates in surface and bottom waters along a closely spaced 4-station transect at 71 W on the North Atlantic continental shelf, in the vicinity of the shelfbreak front. This transect intersects a robust upwelling cell that typically shows high biologic productivity, and is locatable by changes in T/S profiles and chl a concentrations along sharp spatial gradients. At the time of sampling, cold pool waters over the continental shelf were relatively cold, 3.5 Deg. C, compared to 12 Deg. C over the upper continental slope. Satellite thermal imagery indicated that shelf water extended offshore and interacted with a large crest of the Gulf Stream. The surface and bottom waters associated with the upwelling jet were characterized by enzyme activities a factor of 20 more rapid than closer inshore waters, and surface water chl a concentrations that were two to three times higher than the inshore waters. The spectrum of enzyme activities also differed markedly between surface and bottom waters both within the jet and at near-shore stations. Microbial extracellular enzymatic activities were strongly influenced by differences in their environmental context along the continental slope and shelfbreak front. Constraining the factors controlling heterotrophic activity across the diverse marine environment is an important step in understanding microbial controls on carbon cycling.

Activation of AMPK reduces the co-transporter activity of NKCC1.

PubMed

Fraser, Scott A; Davies, Matthew; Katerelos, Marina; Gleich, Kurt; Choy, Suet-Wan; Steel, Rohan; Galic, Sandra; Mount, Peter F; Kemp, Bruce E; Power, David A

2014-01-01

The co-transporter activity of Na(+)-K(+)-2Cl(-) 1 (NKCC1) is dependent on phosphorylation. In this study we show the energy-sensing kinase AMPK inhibits NKCC1 activity. Three separate AMPK activators (AICAR, Phenformin and A-769662) inhibited NKCC1 flux in a variety of nucleated cells. Treatment with A-769662 resulted in a reduction of NKCC1(T212/T217) phosphorylation, and this was reversed by treatment with the non-selective AMPK inhibitor Compound C. AMPK dependence was confirmed by treatment of AMPK null mouse embryonic fibroblasts, where A-769662 had no effect on NKCC1 mediated transport. AMPK was found to directly phosphorylate a recombinant human-NKCC1 N-terminal fragment (1-293) with the phosphorylated site identified as S77. Mutation of Serine 77 to Alanine partially prevented the inhibitory effect of A-769662 on NKCC1 activity. In conclusion, AMPK can act to reduce NKCC1-mediated transport. While the exact mechanism is still unclear there is evidence for both a direct effect on phosphorylation of S77 and reduced phosphorylation of T212/217.

Systematic review of active workplace interventions to reduce sickness absence.

PubMed

Odeen, M; Magnussen, L H; Maeland, S; Larun, L; Eriksen, H R; Tveito, T H

2013-01-01

The workplace is used as a setting for interventions to prevent and reduce sickness absence, regardless of the specific medical conditions and diagnoses. To give an overview of the general effectiveness of active workplace interventions aimed at preventing and reducing sickness absence. We systematically searched PubMed, Embase, Psych-info, and ISI web of knowledge on 27 December 2011. Inclusion criteria were (i) participants over 18 years old with an active role in the intervention, (ii) intervention done partly or fully at the workplace or at the initiative of the workplace and (iii) sickness absence reported. Two reviewers independently screened articles, extracted data and assessed risk of bias. A narrative synthesis was used. We identified 2036 articles of which, 93 were assessed in full text. Seventeen articles were included (2 with low and 15 with medium risk of bias), with a total of 24 comparisons. Five interventions from four articles significantly reduced sickness absence. We found moderate evidence that graded activity reduced sickness absence and limited evidence that the Sheerbrooke model (a comprehensive multidisciplinary intervention) and cognitive behavioural therapy (CBT) reduced sickness absence. There was moderate evidence that workplace education and physical exercise did not reduce sickness absence. For other interventions, the evidence was insufficient to draw conclusions. The review found limited evidence that active workplace interventions were not generally effective in reducing sickness absence, but there was moderate evidence of effect for graded activity and limited evidence for the effectiveness of the Sheerbrooke model and CBT.

Implementation Intentions Reduce Implicit Stereotype Activation and Application.

PubMed

Rees, Heather Rose; Rivers, Andrew Michael; Sherman, Jeffrey W

2018-05-01

Research has found that implementation intentions, if-then action plans (e.g., "if I see a Black face, I will think safe"), reduce stereotyping on implicit measures. However, it is unknown by what process(es) implementation intentions reduce implicit stereotyping. The present research examines the effects of implementation intentions on stereotype activation (e.g., extent to which stereotypic information is accessible) and stereotype application (e.g., extent to which accessible stereotypes are applied in judgment). In addition, we assessed the efficiency of implementation intentions by manipulating cognitive resources (e.g., digit-span, restricted response window) while participants made judgments on an implicit stereotyping measure. Across four studies, implementation intentions reduced implicit stereotyping. This decrease in stereotyping was associated with reductions in both stereotype activation and application. In addition, these effects of implementation intentions were highly efficient and associated with reduced stereotyping even for groups for which people may have little practice inhibiting stereotypes (e.g., gender).

Bringing MapReduce Closer To Data With Active Drives

NASA Astrophysics Data System (ADS)

Golpayegani, N.; Prathapan, S.; Warmka, R.; Wyatt, B.; Halem, M.; Trantham, J. D.; Markey, C. A.

2017-12-01

Moving computation closer to the data location has been a much theorized improvement to computation for decades. The increase in processor performance, the decrease in processor size and power requirement combined with the increase in data intensive computing has created a push to move computation as close to data as possible. We will show the next logical step in this evolution in computing: moving computation directly to storage. Hypothetical systems, known as Active Drives, have been proposed as early as 1998. These Active Drives would have a general-purpose CPU on each disk allowing for computations to be performed on them without the need to transfer the data to the computer over the system bus or via a network. We will utilize Seagate's Active Drives to perform general purpose parallel computing using the MapReduce programming model directly on each drive. We will detail how the MapReduce programming model can be adapted to the Active Drive compute model to perform general purpose computing with comparable results to traditional MapReduce computations performed via Hadoop. We will show how an Active Drive based approach significantly reduces the amount of data leaving the drive when performing several common algorithms: subsetting and gridding. We will show that an Active Drive based design significantly improves data transfer speeds into and out of drives compared to Hadoop's HDFS while at the same time keeping comparable compute speeds as Hadoop.

MLV integration site selection is driven by strong enhancers and active promoters

PubMed Central

LaFave, Matthew C.; Varshney, Gaurav K.; Gildea, Derek E.; Wolfsberg, Tyra G.; Baxevanis, Andreas D.; Burgess, Shawn M.

2014-01-01

Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors. PMID:24464997

Systematic review of active workplace interventions to reduce sickness absence

PubMed Central

2013-01-01

Background The workplace is used as a setting for interventions to prevent and reduce sickness absence, regardless of the specific medical conditions and diagnoses. Aims To give an overview of the general effectiveness of active workplace interventions aimed at preventing and reducing sickness absence. Methods We systematically searched PubMed, Embase, Psych-info, and ISI web of knowledge on 27 December 2011. Inclusion criteria were (i) participants over 18 years old with an active role in the intervention, (ii) intervention done partly or fully at the workplace or at the initiative of the workplace and (iii) sickness absence reported. Two reviewers independently screened articles, extracted data and assessed risk of bias. A narrative synthesis was used. Results We identified 2036 articles of which, 93 were assessed in full text. Seventeen articles were included (2 with low and 15 with medium risk of bias), with a total of 24 comparisons. Five interventions from four articles significantly reduced sickness absence. We found moderate evidence that graded activity reduced sickness absence and limited evidence that the Sheerbrooke model (a comprehensive multidisciplinary intervention) and cognitive behavioural therapy (CBT) reduced sickness absence. There was moderate evidence that workplace education and physical exercise did not reduce sickness absence. For other interventions, the evidence was insufficient to draw conclusions. Conclusions The review found limited evidence that active workplace interventions were not generally effective in reducing sickness absence, but there was moderate evidence of effect for graded activity and limited evidence for the effectiveness of the Sheerbrooke model and CBT. PMID:23223750

A strong pelvic floor is associated with higher rates of sexual activity in women with pelvic floor disorders

PubMed Central

Kanter, Gregg; Rogers, Rebecca G; Pauls, Rachel N; Kammerer-Doak, Dorothy; Thakar, Ranee

2015-01-01

Introduction and Hypothesis We evaluated the associations between pelvic floor muscle strength and tone with sexual activity and sexual function in women with pelvic floor disorders. Methods This was a secondary analysis of a multicenter study of women with pelvic floor disorders from the US and UK performed to validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Participants were surveyed about whether they were sexually active and completed the PISQ-IR and Female Sexual Function Index (FSFI) questionnaires to assess sexual function. Physical exams included assessment of pelvic floor strength by the Oxford Grading Scale, and assessment of pelvic floor tone per ICS guidelines. Results The cohort of 585 women was middle aged (mean age 54.9 +/−12.1) with 395 (67.5%) reporting sexual activity. Women with a strong pelvic floor (n=275) were more likely to report sexual activity than women with weak strength (n=280) (75.3 vs. 61.8%, p<0.001), but normal or hypoactive pelvic floor tone was not associated with sexual activity (68.8 vs. 60.2%, normal vs. hypoactive, p=0.08). After multivariable analysis, a strong pelvic floor remained predictive of sexual activity (OR 1.89, CI 1.18–3.03, p<0.01). Among sexually active women (n=370), a strong pelvic floor was associated with higher scores on the PISQ-IR domain of condition impact (Parameter Estimate 0.20+/−0.09, P=0.04), and FSFI orgasm domain (PE 0.51+/−0.17, P=0.004). Conclusion A strong pelvic floor is associated with higher rates of sexual activity as well as higher sexual function scores on the condition impact domain of the PISQ-IR and orgasm domain of the FSFI. PMID:25994625

Platypus and opossum calcitonins exhibit strong activities, even though they belong to mammals.

PubMed

Yamashita, Teruhito; Udagawa, Nobuyuki; Thirukonda, Gnanasagar Janardhanan; Uehara, Shunsuke; Yamauchi, Hirose; Suzuki, Nobuo; Li, Feng; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2017-05-15

In mammalian assay systems, calcitonin peptides of non-mammalian species exhibit stronger activity than those of mammals. Recently, comparative analyses of a wide-range of species revealed that platypus and opossum, which diverged early from other mammals, possess calcitonins that are more similar in amino acid sequence to those of non-mammals than mammals. We herein determined whether platypus and opossum calcitonins exhibit similar biological activities to those of non-mammalian calcitonins using an assay of actin ring formation in mouse osteoclasts. We also compared the dose-dependent effects of each calcitonin on cAMP production in osteoclasts. Consistent with the strong similarities in their primary amino acid sequences, platypus and opossum calcitonins disrupted actin rings with similar efficacies to that of salmon calcitonin. Human calcitonin exhibited the weakest inhibitory potency and required a 100-fold higher concentration (EC 50 =3×10 -11 M) than that of salmon calcitonin (EC 50 =2×10 -13 M). Platypus and opossum calcitonins also induced cAMP production in osteoclast cultures with the same efficacies as that of salmon calcitonin. Thus, platypus and opossum calcitonins exhibited strong biological activities, similar to those of the salmon. In addition, phylogenetic analysis revealed that platypus and opossum calcitonins clustered with the salmon-type group but not human- or porcine-type group. These results suggest that platypus and opossum calcitonins are classified into the salmon-type group, in terms of the biological activities and amino acid sequences. Copyright © 2017 Elsevier Inc. All rights reserved.

The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

PubMed Central

Thaa, Bastian; Amrun, Siti Naqiah; Simarmata, Diane; Rausalu, Kai; Nyman, Tuula A.; Merits, Andres; McInerney, Gerald M.; Ng, Lisa F. P.

2016-01-01

ABSTRACT Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated

Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

PubMed Central

Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

2013-01-01

Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

The FRIGIDA Complex Activates Transcription of FLC, a Strong Flowering Repressor in Arabidopsis, by Recruiting Chromatin Modification Factors[C][W

PubMed Central

Choi, Kyuha; Kim, Juhyun; Hwang, Hyun-Ju; Kim, Sanghee; Park, Chulmin; Kim, Sang Yeol; Lee, Ilha

2011-01-01

The flowering of Arabidopsis thaliana winter annuals is delayed until the subsequent spring by the strong floral repressor FLOWERING LOCUS C (FLC). FRIGIDA (FRI) activates the transcription of FLC, but the molecular mechanism remains elusive. The fri mutation causes early flowering with reduced FLC expression similar to frl1, fes1, suf4, and flx, which are mutants of FLC-specific regulators. Here, we report that FRI acts as a scaffold protein interacting with FRL1, FES1, SUF4, and FLX to form a transcription activator complex (FRI-C). Each component of FRI-C has a specialized function. SUF4 binds to a cis-element of the FLC promoter, FLX and FES1 have transcriptional activation potential, and FRL1 and FES1 stabilize the complex. FRI-C recruits a general transcription factor, a TAF14 homolog, and chromatin modification factors, the SWR1 complex and SET2 homolog. Complex formation was confirmed by the immunoprecipitation of FRI-associated proteins followed by mass spectrometric analysis. Our results provide insight into how a specific transcription activator recruits chromatin modifiers to regulate a key flowering gene. PMID:21282526

Myo-inositol reduces β-catenin activation in colitis.

PubMed

Bradford, Emily M; Thompson, Corey A; Goretsky, Tatiana; Yang, Guang-Yu; Rodriguez, Luz M; Li, Linheng; Barrett, Terrence A

2017-07-28

To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin S552 as a biomarker of recurrent dysplasia. We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin S552 and pAkt levels by histology and western blot in IL-10 -/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin S552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. In mice, pβ-catenin S552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pβ-catenin S552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. Enumerating crypts with increased numbers of pβ-catenin S552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.

Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

PubMed

Koch, Marcus W; Zabad, Rana; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V

2015-11-15

Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing reagents – real hits or promiscuous artifacts?

PubMed Central

Johnston, Paul A.

2010-01-01

Redox cycling compounds (RCCs) generate µM concentrations of hydrogen peroxide (H2O2) in the presence of strong reducing agents, common buffer components used to maintain the catalytic activity and/or folding of target proteins for high throughput screening (HTS) assays. H2O2 generated by RCCs can indirectly inhibit the catalytic activity of proteins by oxidizing accessible cysteine, tryptophan, methionine, histidine or selenocysteine residues, and indeed several important classes of protein targets are susceptible to H2O2-mediated inactivation; protein tyrosine phosphatases, cysteine proteases, and metalloenzymes. The main sources of H2O2 in cells are the Nox enzyme/SOD systems, peroxisome metabolism, and the autoxidation of reactive chemicals by enzyme mediated redox cycling at both the microsomal and mitochondrial sites of electron transport. Given the role of H2O2 as a second messenger involved in the regulation of many signaling pathways it is hardly surprising that compounds which can generate intracellular H2O2 by enzyme mediated redox cycling would have pleiotropic effects. RCCs can therefore have serious negative consequences for the probe and/or lead generation process: primary HTS assay hit rates may be inflated by RCC false positives; critical resources will be diverted to develop and implement follow up assays to distinguish RCCs from real hits; and screening databases will become annotated with the promiscuous activity of RCCs. In an attempt to mitigate the serious impact of RCCs on probe and lead generation, two groups have independently developed assays to indentify RCCs. PMID:21075044

Myo-inositol reduces β-catenin activation in colitis

PubMed Central

Bradford, Emily M; Thompson, Corey A; Goretsky, Tatiana; Yang, Guang-Yu; Rodriguez, Luz M; Li, Linheng; Barrett, Terrence A

2017-01-01

AIM To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-cateninS552 as a biomarker of recurrent dysplasia. METHODS We examined the effects of dietary myo-inositol treatment on inflammation, pβ-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, pβ-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pβ-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION Enumerating crypts with increased numbers of pβ-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials. PMID:28811707

The appetite suppressant d-fenfluramine reduces water intake, but not food intake, in activity-based anorexia.

PubMed

Hillebrand, J J G; Heinsbroek, A C M; Kas, M J H; Adan, R A H

2006-02-01

Biochemical, genetic and imaging studies support the involvement of the serotonin (5-HT) system in anorexia nervosa. Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa, and combines scheduled feeding with voluntary running wheel activity (RWA). We investigated the effect of d-fenfluramine (d-FEN) treatment on development and propagation of ABA. d-FEN is an appetite suppressant and acts on 5-HT(2C) receptors that are located on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. Since stimulation activation of the melanocortin system stimulates ABA, we hypothesized that d-FEN treatment enhances the development and propagation of ABA. Rats were exposed to the ABA model and chronically infused with d-FEN. Unexpectedly, d-FEN-treated ABA rats did not reduce food intake or increase wheel running as compared with vehicle-treated ABA rats. Furthermore d-FEN treatment did not affect body weight loss, hypothalamus-pituitary-adrenal axis activation, or starvation-induced hypothermia in ABA rats. POMC mRNA levels in d-FEN-treated rats were not different from vehicle-treated rats after one week of exposure to the ABA paradigm. However, d-FEN-treated ABA rats showed hypodypsia and increased plasma osmolality and arginine-vasopressin expression levels in the hypothalamus. We conclude that d-FEN treatment does not enhance ABA under the experimental conditions of this study, but strongly reduces water intake in ABA rats.

Active control strategy for the running attitude of high-speed train under strong crosswind condition

NASA Astrophysics Data System (ADS)

Li, Decang; Meng, Jianjun; Bai, Huan; Xu, Ruxun

2018-07-01

This paper focuses on the safety of high-speed trains under strong crosswind conditions. A new active control strategy is proposed based on the adaptive predictive control theory. The new control strategy aims at adjusting the attitudes of a train by controlling the new-type intelligent giant magnetostrictive actuator (GMA). It combined adaptive control with dynamic matrix control; parameters of predictive controller was real-time adjusted by online distinguishing to enhance the robustness of the control algorithm. On this basis, a correction control algorithm is also designed to regulate the parameters of predictive controller based on the step response of a controlled objective. Finally, the simulation results show that the proposed control strategy can adjust the running attitudes of high-speed trains under strong crosswind conditions; they also indicate that the new active control strategy is effective and applicable in improving the safety performance of a train based on a host-target computer technology provided by Matlab/Simulink.

Reduced auditory efferent activity in childhood selective mutism.

PubMed

Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

2004-06-01

Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

PubMed Central

Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

2013-01-01

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

Enhanced summer warming reduces fungal decomposer diversity and litter mass loss more strongly in dry than in wet tundra.

PubMed

Christiansen, Casper T; Haugwitz, Merian S; Priemé, Anders; Nielsen, Cecilie S; Elberling, Bo; Michelsen, Anders; Grogan, Paul; Blok, Daan

2017-01-01

Many Arctic regions are currently experiencing substantial summer and winter climate changes. Litter decomposition is a fundamental component of ecosystem carbon and nutrient cycles, with fungi being among the primary decomposers. To assess the impacts of seasonal climatic changes on litter fungal communities and their functioning, Betula glandulosa leaf litter was surface-incubated in two adjacent low Arctic sites with contrasting soil moisture regimes: dry shrub heath and wet sedge tundra at Disko Island, Greenland. At both sites, we investigated the impacts of factorial combinations of enhanced summer warming (using open-top chambers; OTCs) and deepened snow (using snow fences) on surface litter mass loss, chemistry and fungal decomposer communities after approximately 1 year. Enhanced summer warming significantly restricted litter mass loss by 32% in the dry and 17% in the wet site. Litter moisture content was significantly reduced by summer warming in the dry, but not in the wet site. Likewise, fungal total abundance and diversity were reduced by OTC warming at the dry site, while comparatively modest warming effects were observed in the wet site. These results suggest that increased evapotranspiration in the OTC plots lowered litter moisture content to the point where fungal decomposition activities became inhibited. In contrast, snow addition enhanced fungal abundance in both sites but did not significantly affect litter mass loss rates. Across sites, control plots only shared 15% of their fungal phylotypes, suggesting strong local controls on fungal decomposer community composition. Nevertheless, fungal community functioning (litter decomposition) was negatively affected by warming in both sites. We conclude that although buried soil organic matter decomposition is widely expected to increase with future summer warming, surface litter decay and nutrient turnover rates in both xeric and relatively moist tundra are likely to be significantly restricted by

Strong Hearts, healthy communities: a rural community-based cardiovascular disease prevention program.

PubMed

Seguin, Rebecca A; Eldridge, Galen; Graham, Meredith L; Folta, Sara C; Nelson, Miriam E; Strogatz, David

2016-01-28

Cardiovascular disease is the leading cause of death in the United States and places substantial burden on the health care system. Rural populations, especially women, have considerably higher rates of cardiovascular disease, influenced by poverty, environmental factors, access to health care, and social and cultural attitudes and norms. This community-based study will be a two-arm randomized controlled efficacy trial comparing a multi-level, community program (Strong Hearts, Healthy Communities) with a minimal intervention control program (Strong Hearts, Healthy Women). Strong Hearts, Healthy Communities was developed by integrating content from three evidence-based programs and was informed by extensive formative research (e.g. community assessments, focus groups, and key informant interviews). Classes will meet twice weekly for one hour for 24 weeks and focus on individual-level skill building and behavior change; social and civic engagement are also core programmatic elements. Strong Hearts, Healthy Women will meet monthly for hour-long sessions over the 24 weeks covering similar content in a general, condensed format. Overweight, sedentary women 40 years of age and older from rural, medically underserved communities (12 in Montana and 4 in New York) will be recruited; sites, pair-matched based on rurality, will be randomized to full or minimal intervention. Data will be collected at baseline, midpoint, intervention completion, and six-month, one-year, and eighteen months post-intervention. The primary outcome is change in body weight; secondary outcomes include physiologic, anthropometric, behavioral, and psychosocial variables. In the full intervention, engagement of participants' friends and family members in partnered activities and community events is an intervention target, hypothesizing that there will be a reciprocal influence of physical activity and diet behavior between participants and their social network. Family members and/or friends will be

Reduced energy availability: implications for bone health in physically active populations.

PubMed

Papageorgiou, Maria; Dolan, Eimear; Elliott-Sale, Kirsty J; Sale, Craig

2018-04-01

The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Adsorbate-mediated strong metal–support interactions in oxide-supported Rh catalysts

DOE PAGES

Matsubu, John C.; Zhang, Shuyi; DeRita, Leo; ...

2016-09-19

The optimization of supported metal catalysts predominantly focuses on engineering the metal site, for which physical insights based on extensive theoretical and experimental contributions have enabled the rational design of active sites. Although it is well known that supports can influence the catalytic properties of metals, insights into how metal–support interactions can be exploited to optimize metal active-site properties are lacking. Here in this paper, we utilize in situ spectroscopy and microscopy to identify and characterize a support effect in oxide-supported heterogeneous Rh catalysts. This effect is characterized by strongly bound adsorbates (HCO x) on reducible oxide supports (TiO 2more » and Nb 2O 5) that induce oxygen-vacancy formation in the support and cause HCO x-functionalized encapsulation of Rh nanoparticles by the support. The encapsulation layer is permeable to reactants, stable under the reaction conditions and strongly influences the catalytic properties of Rh, which enables rational and dynamic tuning of CO 2-reduction selectivity.« less

Prostate Cancer Patient Characteristics Associated With a Strong Preference to Preserve Sexual Function and Receipt of Active Surveillance.

PubMed

Broughman, James R; Basak, Ramsankar; Nielsen, Matthew E; Reeve, Bryce B; Usinger, Deborah S; Spearman, Kiayni C; Godley, Paul A; Chen, Ronald C

2018-04-01

Men with early-stage prostate cancer have multiple options that have similar oncologic efficacy but vary in terms of their impact on quality of life. In low-risk cancer, active surveillance is the option that best preserves patients' sexual function, but it is unknown if patient preference affects treatment selection. Our objectives were to identify patient characteristics associated with a strong preference to preserve sexual function and to determine whether patient preference and baseline sexual function level are associated with receipt of active surveillance in low-risk cancer. In this population-based cohort of men with localized prostate cancer, baseline patient-reported sexual function was assessed using a validated instrument. Patients were also asked whether preservation of sexual function was very, somewhat, or not important. Prostate cancer disease characteristics and treatments received were abstracted from medical records. A modified Poisson regression model with robust standard errors was used to compute adjusted risk ratio (aRR) estimates. All statistical tests were two-sided. Among 1194 men, 52.6% indicated a strong preference for preserving sexual function. Older men were less likely to have a strong preference (aRR = 0.98 per year, 95% confidence interval [CI] = 0.97 to 0.99), while men with normal sexual function were more likely (vs poor function, aRR = 1.59, 95% CI = 1.39 to 1.82). Among 568 men with low-risk cancer, there was no clear association between baseline sexual function or strong preference to preserve function with receipt of active surveillance. However, strong preference may differnetially impact those with intermediate baseline function vs poor function (Pinteraction = .02). Treatment choice may not always align with patients' preferences. These findings demonstrate opportunities to improve delivery of patient-centered care in early prostate cancer.

Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages.

PubMed

Bae, Deok Sung; Kim, Young Hoon; Pan, Cheol-Ho; Nho, Chu Won; Samdan, Javzan; Yansan, Jamyansan; Lee, Jae Kown

2012-02-01

Protopine is an isoquinoline alkaloid contained in plants in northeast Asia. In this study, we investigated whether protopine derived from Hypecoum erectum L could suppress lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (Raw 264.7 cells). Protopine was found to reduce nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E(2) (PGE(2)) production by LPS-stimulated Raw 264.7 cells, without a cytotoxic effect. Pre-treatment of Raw 264.7 cells with protopine reduced the production of pro-inflammatory cytokines. These inhibitory effects were caused by blocking phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocking activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

Generalized-active-space pair-density functional theory: an efficient method to study large, strongly correlated, conjugated systems.

PubMed

Ghosh, Soumen; Cramer, Christopher J; Truhlar, Donald G; Gagliardi, Laura

2017-04-01

Predicting ground- and excited-state properties of open-shell organic molecules by electronic structure theory can be challenging because an accurate treatment has to correctly describe both static and dynamic electron correlation. Strongly correlated systems, i.e. , systems with near-degeneracy correlation effects, are particularly troublesome. Multiconfigurational wave function methods based on an active space are adequate in principle, but it is impractical to capture most of the dynamic correlation in these methods for systems characterized by many active electrons. We recently developed a new method called multiconfiguration pair-density functional theory (MC-PDFT), that combines the advantages of wave function theory and density functional theory to provide a more practical treatment of strongly correlated systems. Here we present calculations of the singlet-triplet gaps in oligoacenes ranging from naphthalene to dodecacene. Calculations were performed for unprecedently large orbitally optimized active spaces of 50 electrons in 50 orbitals, and we test a range of active spaces and active space partitions, including four kinds of frontier orbital partitions. We show that MC-PDFT can predict the singlet-triplet splittings for oligoacenes consistent with the best available and much more expensive methods, and indeed MC-PDFT may constitute the benchmark against which those other models should be compared, given the absence of experimental data.

Polyvinylpyrrolidone stabilized-Ru nanoclusters loaded onto reduced graphene oxide as high active catalyst for hydrogen evolution

NASA Astrophysics Data System (ADS)

Zhang, Jiao; Hao, Jinghao; Ma, Qianli; Li, Chuanqi; Liu, Yushan; Li, Baojun; Liu, Zhongyi

2017-06-01

Ruthenium/reduced graphene oxide nanocomposites (Ru/rGO NCs) were synthesized via an electrostatic self-assembly approach. Polyvinylpyrrolidone (PVP) stabilized and positively charged metallic ruthenium nanoclusters about 1.2 nm were synthesized and uniformly loaded onto negatively charged graphene oxide (GO) sheets via strong electrostatic interactions. The as-prepared Ru/rGO NCs exhibited superior performance in catalytic hydrolysis of sodium borohydride (NaBH4) to generate H2. The hydrogen generation rate was up to 14.87 L H2 min-1 gcat -1 at 318 K with relatively low activation energy of 38.12 kJ mol-1. Kinetics study confirmed that the hydrolysis of NaBH4 was first order with respect to concentration of catalysts. Besides, the conversion of NaBH4 remained at 97% and catalytic activity retained more than 70% after 5 reaction cycles at room temperature. These results suggested that the Ru/rGO NCs have a promising prospect in the field of clean energy.

Strongly contracted canonical transformation theory

NASA Astrophysics Data System (ADS)

Neuscamman, Eric; Yanai, Takeshi; Chan, Garnet Kin-Lic

2010-01-01

Canonical transformation (CT) theory describes dynamic correlation in multireference systems with large active spaces. Here we discuss CT theory's intruder state problem and why our previous approach of overlap matrix truncation becomes infeasible for sufficiently large active spaces. We propose the use of strongly and weakly contracted excitation operators as alternatives for dealing with intruder states in CT theory. The performance of these operators is evaluated for the H2O, N2, and NiO molecules, with comparisons made to complete active space second order perturbation theory and Davidson-corrected multireference configuration interaction theory. Finally, using a combination of strongly contracted CT theory and orbital-optimized density matrix renormalization group theory, we evaluate the singlet-triplet gap of free base porphin using an active space containing all 24 out-of-plane 2p orbitals. Modeling dynamic correlation with an active space of this size is currently only possible using CT theory.

Dynamics of self-sustained asynchronous-irregular activity in random networks of spiking neurons with strong synapses

PubMed Central

Kriener, Birgit; Enger, Håkon; Tetzlaff, Tom; Plesser, Hans E.; Gewaltig, Marc-Oliver; Einevoll, Gaute T.

2014-01-01

Random networks of integrate-and-fire neurons with strong current-based synapses can, unlike previously believed, assume stable states of sustained asynchronous and irregular firing, even without external random background or pacemaker neurons. We analyze the mechanisms underlying the emergence, lifetime and irregularity of such self-sustained activity states. We first demonstrate how the competition between the mean and the variance of the synaptic input leads to a non-monotonic firing-rate transfer in the network. Thus, by increasing the synaptic coupling strength, the system can become bistable: In addition to the quiescent state, a second stable fixed-point at moderate firing rates can emerge by a saddle-node bifurcation. Inherently generated fluctuations of the population firing rate around this non-trivial fixed-point can trigger transitions into the quiescent state. Hence, the trade-off between the magnitude of the population-rate fluctuations and the size of the basin of attraction of the non-trivial rate fixed-point determines the onset and the lifetime of self-sustained activity states. During self-sustained activity, individual neuronal activity is moreover highly irregular, switching between long periods of low firing rate to short burst-like states. We show that this is an effect of the strong synaptic weights and the finite time constant of synaptic and neuronal integration, and can actually serve to stabilize the self-sustained state. PMID:25400575

Dynamics of self-sustained asynchronous-irregular activity in random networks of spiking neurons with strong synapses.

PubMed

Kriener, Birgit; Enger, Håkon; Tetzlaff, Tom; Plesser, Hans E; Gewaltig, Marc-Oliver; Einevoll, Gaute T

2014-01-01

Random networks of integrate-and-fire neurons with strong current-based synapses can, unlike previously believed, assume stable states of sustained asynchronous and irregular firing, even without external random background or pacemaker neurons. We analyze the mechanisms underlying the emergence, lifetime and irregularity of such self-sustained activity states. We first demonstrate how the competition between the mean and the variance of the synaptic input leads to a non-monotonic firing-rate transfer in the network. Thus, by increasing the synaptic coupling strength, the system can become bistable: In addition to the quiescent state, a second stable fixed-point at moderate firing rates can emerge by a saddle-node bifurcation. Inherently generated fluctuations of the population firing rate around this non-trivial fixed-point can trigger transitions into the quiescent state. Hence, the trade-off between the magnitude of the population-rate fluctuations and the size of the basin of attraction of the non-trivial rate fixed-point determines the onset and the lifetime of self-sustained activity states. During self-sustained activity, individual neuronal activity is moreover highly irregular, switching between long periods of low firing rate to short burst-like states. We show that this is an effect of the strong synaptic weights and the finite time constant of synaptic and neuronal integration, and can actually serve to stabilize the self-sustained state.

Photoprotection, photosynthesis and growth of tropical tree seedlings under near-ambient and strongly reduced solar ultraviolet-B radiation.

PubMed

Krause, G Heinrich; Jahns, Peter; Virgo, Aurelio; García, Milton; Aranda, Jorge; Wellmann, Eckard; Winter, Klaus

2007-10-01

Seedlings of two late-successional tropical rainforest tree species, Tetragastris panamensis (Engler) O. Kuntze and Calophyllum longifolium (Willd.), were field grown for 3-4 months at an open site near Panama City (9 degrees N), Panama, under plastic films that either transmitted or excluded most solar UV-B radiation. Experiments were designed to test whether leaves developing under bright sunlight with strongly reduced UV-B are capable of acclimating to near-ambient UV-B conditions. Leaves of T. panamensis that developed under near-ambient UV-B contained higher amounts of UV-absorbing substances than leaves of seedlings grown under reduced UV-B. Photosynthetic pigment composition, content of alpha-tocopherol, CO(2) assimilation, potential photosystem II (PSII) efficiency (evaluated by F(v)/F(m) ratios) and growth of T. panamensis and C. longifolium did not differ between seedlings developed under near-ambient and reduced solar UV-B. When seedlings were transferred from the reduced UV-B treatment to the near-ambient UV-B treatment, a pronounced inhibition of photosynthetic capacity was observed initially in both species. UV-B-mediated inhibition of photosynthetic capacity nearly fully recovered within 1 week of the transfer in C. longifolium, whereas in T. panamensis an about 35% reduced capacity of CO(2) uptake was maintained. A marked increase in UV-absorbing substances was observed in foliage of transferred T. panamensis seedlings. Both species exhibited enhanced mid-day photoinhibition of PSII immediately after being transferred from the reduced UV-B to the near-ambient UV-B treatment. This effect was fully reversible within 1d in T. panamensis and within a few days in C. longifolium. The data show that leaves of these tropical tree seedlings, when developing in full-spectrum sunlight, are effectively protected against high solar UV-B radiation. In contrast, leaves developing under conditions of low UV-B lacked sufficient UV protection. They experienced a

Active learning reduces annotation time for clinical concept extraction.

PubMed

Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

2017-10-01

To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

Generalized-active-space pair-density functional theory: an efficient method to study large, strongly correlated, conjugated systems

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

Ghosh, Soumen; Cramer, Christopher J.; Truhlar, Donald G.

Predicting ground- and excited-state properties of open-shell organic molecules by electronic structure theory can be challenging because an accurate treatment has to correctly describe both static and dynamic electron correlation. Strongly correlated systems, i.e., systems with near-degeneracy correlation effects, are particularly troublesome. Multiconfigurational wave function methods based on an active space are adequate in principle, but it is impractical to capture most of the dynamic correlation in these methods for systems characterized by many active electrons. Here, we recently developed a new method called multiconfiguration pair-density functional theory (MC-PDFT), that combines the advantages of wave function theory and density functionalmore » theory to provide a more practical treatment of strongly correlated systems. Here we present calculations of the singlet–triplet gaps in oligoacenes ranging from naphthalene to dodecacene. Calculations were performed for unprecedently large orbitally optimized active spaces of 50 electrons in 50 orbitals, and we test a range of active spaces and active space partitions, including four kinds of frontier orbital partitions. We show that MC-PDFT can predict the singlet–triplet splittings for oligoacenes consistent with the best available and much more expensive methods, and indeed MC-PDFT may constitute the benchmark against which those other models should be compared, given the absence of experimental data.« less

Generalized-active-space pair-density functional theory: an efficient method to study large, strongly correlated, conjugated systems

DOE PAGES

Ghosh, Soumen; Cramer, Christopher J.; Truhlar, Donald G.; ...

2017-01-19

Predicting ground- and excited-state properties of open-shell organic molecules by electronic structure theory can be challenging because an accurate treatment has to correctly describe both static and dynamic electron correlation. Strongly correlated systems, i.e., systems with near-degeneracy correlation effects, are particularly troublesome. Multiconfigurational wave function methods based on an active space are adequate in principle, but it is impractical to capture most of the dynamic correlation in these methods for systems characterized by many active electrons. Here, we recently developed a new method called multiconfiguration pair-density functional theory (MC-PDFT), that combines the advantages of wave function theory and density functionalmore » theory to provide a more practical treatment of strongly correlated systems. Here we present calculations of the singlet–triplet gaps in oligoacenes ranging from naphthalene to dodecacene. Calculations were performed for unprecedently large orbitally optimized active spaces of 50 electrons in 50 orbitals, and we test a range of active spaces and active space partitions, including four kinds of frontier orbital partitions. We show that MC-PDFT can predict the singlet–triplet splittings for oligoacenes consistent with the best available and much more expensive methods, and indeed MC-PDFT may constitute the benchmark against which those other models should be compared, given the absence of experimental data.« less

Fatigue-related firing of distal muscle nociceptors reduces voluntary activation of proximal muscles of the same limb.

PubMed

Kennedy, David S; McNeil, Chris J; Gandevia, Simon C; Taylor, Janet L

2014-02-15

With fatiguing exercise, firing of group III/IV muscle afferents reduces voluntary activation and force of the exercised muscles. These afferents can also act across agonist/antagonist pairs, reducing voluntary activation and force in nonfatigued muscles. We hypothesized that maintained firing of group III/IV muscle afferents after a fatiguing adductor pollicis (AP) contraction would decrease voluntary activation and force of AP and ipsilateral elbow flexors. In two experiments (n = 10) we examined voluntary activation of AP and elbow flexors by measuring changes in superimposed twitches evoked by ulnar nerve stimulation and transcranial magnetic stimulation of the motor cortex, respectively. Inflation of a sphygmomanometer cuff after a 2-min AP maximal voluntary contraction (MVC) blocked circulation of the hand for 2 min and maintained firing of group III/IV muscle afferents. After a 2-min AP MVC, maximal AP voluntary activation was lower with than without ischemia (56.2 ± 17.7% vs. 76.3 ± 14.6%; mean ± SD; P < 0.05) as was force (40.3 ± 12.8% vs. 57.1 ± 13.8% peak MVC; P < 0.05). Likewise, after a 2-min AP MVC, elbow flexion voluntary activation was lower with than without ischemia (88.3 ± 7.5% vs. 93.6 ± 3.9%; P < 0.05) as was torque (80.2 ± 4.6% vs. 86.6 ± 1.0% peak MVC; P < 0.05). Pain during ischemia was reported as Moderate to Very Strong. Postfatigue firing of group III/IV muscle afferents from the hand decreased voluntary drive and force of AP. Moreover, this effect decreased voluntary drive and torque of proximal unfatigued muscles, the elbow flexors. Fatigue-sensitive group III/IV muscle nociceptors act to limit voluntary drive not only to fatigued muscles but also to unfatigued muscles within the same limb.

Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

PubMed

Ng, Wan-Fai; Miller, Ariana; Bowman, Simon J; Price, Elizabeth J; Kitas, George D; Pease, Colin; Emery, Paul; Lanyon, Peter; Hunter, John; Gupta, Monica; Giles, Ian; Isenberg, David; McLaren, John; Regan, Marian; Cooper, Annie; Young-Min, Steven A; McHugh, Neil; Vadivelu, Saravanan; Moots, Robert J; Coady, David; MacKay, Kirsten; Dasgupta, Bhaskar; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; Griffiths, Bridget; Mitchell, Sheryl; Miyamoto, Samira Tatiyama; Trenell, Michael

2017-04-01

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

PubMed

Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Enhancing lithium-sulphur battery performance by strongly binding the discharge products on amino-functionalized reduced graphene oxide.

PubMed

Wang, Zhiyu; Dong, Yanfeng; Li, Hongjiang; Zhao, Zongbin; Wu, Hao Bin; Hao, Ce; Liu, Shaohong; Qiu, Jieshan; Lou, Xiong Wen David

2014-09-25

Lithium-sulphur batteries are one very appealing power source with high energy density. But their practical use is still hindered by several issues including short lifespan, low efficiency and safety concern from the lithium anode. Polysulphide dissolution and insulating nature of sulphur are generally considered responsible for the capacity degradation. However, the detachment of discharge products, that is, highly polar lithium sulphides, from nonpolar carbon matrix (for example, graphene) has been rarely studied as one critical factor. Here we report the strongly covalent stabilization of sulphur and its discharge products on amino-functionalized reduced graphene oxide that enables stable capacity retention of 80% for 350 cycles with high capacities and excellent high-rate response up to 4 C. The present study demonstrates a feasible and effective strategy to solve the long-term cycling difficulty for lithium-sulphur batteries and also helps to understand the capacity decay mechanism involved.

n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels.

PubMed

Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

2017-03-13

Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n -hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

Strongly correlated perovskite fuel cells

NASA Astrophysics Data System (ADS)

Zhou, You; Guan, Xiaofei; Zhou, Hua; Ramadoss, Koushik; Adam, Suhare; Liu, Huajun; Lee, Sungsik; Shi, Jian; Tsuchiya, Masaru; Fong, Dillon D.; Ramanathan, Shriram

2016-06-01

Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.

Strongly correlated perovskite fuel cells.

PubMed

Zhou, You; Guan, Xiaofei; Zhou, Hua; Ramadoss, Koushik; Adam, Suhare; Liu, Huajun; Lee, Sungsik; Shi, Jian; Tsuchiya, Masaru; Fong, Dillon D; Ramanathan, Shriram

2016-06-09

Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.

Short-duration therapeutic massage reduces postural upper trapezius muscle activity.

PubMed

Domingo, Antoinette R; Diek, Melissa; Goble, Kathleen M; Maluf, Katrina S; Goble, Daniel J; Baweja, Harsimran S

2017-01-18

Massage therapy has historically been used as a therapeutic treatment to help reduce pain and promote relaxation. The aim of this study was to investigate the effect of therapeutic massage on the upper trapezius muscles, which are commonly associated with increased muscle tension. This was a randomized crossover study. Seventeen healthy individuals (nine women; 24.5±4.0 years) participated in the study. All individuals participated in two sessions that were held 24 h apart. In one of the sessions, the participants received a moderate pressure massage applied to the shoulders and neck. In the other session, participants sat quietly. The order of the sessions was counterbalanced across participants. Muscle activity, as measured by surface electromyography, of the upper trapezius muscles was recorded. The amount of muscle activity change following massage was compared with the change in muscle activity following quiet sitting. Muscle activity of the upper trapezius reduced significantly (19.3%; P=0.004) following massage compared with muscle activity following quiet sitting (1.0%). Our findings suggest that short-duration moderate pressure massage leads to a reduction in upper trapezius muscle activity. This result has potential implications for clinical populations such as those with chronic neck pain.

Strong Coupling Corrections in Quantum Thermodynamics

NASA Astrophysics Data System (ADS)

Perarnau-Llobet, M.; Wilming, H.; Riera, A.; Gallego, R.; Eisert, J.

2018-03-01

Quantum systems strongly coupled to many-body systems equilibrate to the reduced state of a global thermal state, deviating from the local thermal state of the system as it occurs in the weak-coupling limit. Taking this insight as a starting point, we study the thermodynamics of systems strongly coupled to thermal baths. First, we provide strong-coupling corrections to the second law applicable to general systems in three of its different readings: As a statement of maximal extractable work, on heat dissipation, and bound to the Carnot efficiency. These corrections become relevant for small quantum systems and vanish in first order in the interaction strength. We then move to the question of power of heat engines, obtaining a bound on the power enhancement due to strong coupling. Our results are exemplified on the paradigmatic non-Markovian quantum Brownian motion.

Heparanase level and procoagulant activity are reduced in severe sepsis.

PubMed

Matan, Moshe; King, Daniel; Peled, Eli; Ackerman, Shanny; Bar-Lavi, Yaron; Brenner, Benjamin; Nadir, Yona

2018-02-01

During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. Twenty-one patients with non-trauma, non-surgical sepsis admitted to the intensive care unit and 35 controls were recruited. Plasma samples were drawn from the study participants on days 1 and 7 following admission. Heparanase levels and procoagulant activity on day 1 were significantly reduced in patients compared to controls (P < .0001, P < .0001, respectively). Day 1 heparanase procoagulant activity ≥350 ng/mL yielded a negative predictive value for severe sepsis of 89%. Additionally, heparanase procoagulant activity on day 7 correlated with the change in the APACHE score between days 1 and 7 (r = .66, P = .007). Heparanase procoagulant activity decreases during sepsis and returns to normal levels as soon as the patient recovers. Hence, it can be potentially used to predict the risk of severe sepsis. These findings need to be further explored in large-scale studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of short-term reduced physical activity on cardiovascular risk factors in active lean and overweight middle-aged men.

PubMed

Dixon, Natalie C; Hurst, Tina L; Talbot, Duncan C S; Tyrrell, Rex M; Thompson, Dylan

2013-03-01

An experimental reduction in physical activity is a useful tool for exploring the health benefits of physical activity. This study investigated whether similarly-active overweight men show a more pronounced response to reduced physical activity than their lean counterparts because of their atherogenic phenotype (i.e., greater abdominal adiposity). From 115 active men aged 45-64years, we recruited nine active lean (waist circumference <84cm) and nine active central overweight men (waist circumference >94cm). Fasting blood samples and responses to an oral glucose tolerance test (OGTT) were measured at baseline and following one week of reduced physical activity to simulate sedentary levels (removal of structured exercise and reduced habitual physical activity). Glucose and insulin areas under the curve (AUC), CRP, ALT, TAG were all higher in the overweight group and remained so throughout (P<0.05). Insulin and glucose AUC responses to an OGTT, as well as fasting triglyceride (TAG) concentrations, increased in both groups as a result of the intervention (P<0.05). There was no change in interleukin-6, C-reactive protein (CRP), Tumour Necrosis Factor-α, soluble intracellular adhesion molecule 1, or alanine transaminase (ALT). One-week of reduced activity similarly-impaired glucose control and increased fasting TAG in both lean and overweight men. Importantly, in spite of very similar (high) levels of habitual physical activity, central overweight men displayed a poorer profile for various inflammatory and metabolic outcomes (CRP, ALT, TAG, glucose AUC and insulin AUC). Copyright © 2013 Elsevier Inc. All rights reserved.

Wheel running reduces ethanol seeking by increasing neuronal activation and reducing oligodendroglial/neuroinflammatory factors in the medial prefrontal cortex

PubMed Central

Somkuwar, Sucharita S.; Fannon, McKenzie J.; Ghofranian, Atoosa; Quigley, Jacqueline A.; Dutta, Rahul R.; Galinato, Melissa H.; Mandyam, Chitra D.

2016-01-01

The therapeutic effects of wheel running (WR) during abstinence on reinstatement of ethanol seeking behaviors in rats that self-administered ethanol only (ethanol drinking, ED) or ED with concurrent chronic intermittent ethanol vapor experience (CIE-ED) were investigated. Neuronal activation as well as oligodendroglial and neuroinflammatory factors were measured in the medial prefrontal cortex (mPFC) tissue to determine cellular correlates associated with enhanced ethanol seeking. CIE-ED rats demonstrated escalated and unregulated intake of ethanol and maintained higher drinking than ED rats during abstinence. CIE-ED rats were more resistant to extinction from ethanol self-administration, however, demonstrated similar ethanol seeking triggered by ethanol contextual cues compared to ED rats. Enhanced seeking was associated with reduced neuronal activation, and increased number of myelinating oligodendrocyte progenitors and PECAM-1 expression in the mPFC, indicating enhanced oligodendroglial and neuroinflammatory response during abstinence. WR during abstinence enhanced self-administration in ED rats, indicating a deprivation effect. WR reduced reinstatement of ethanol seeking in CIE-ED and ED rats, indicating protection against relapse. The reduced ethanol seeking was associated with enhanced neuronal activation, reduced number of myelinating oligodendrocyte progenitors, and reduced PECAM-1 expression. The current findings demonstrate a protective role of WR during abstinence in reducing ethanol seeking triggered by ethanol contextual cues and establish a role for oligodendroglia-neuroinflammatory response in ethanol seeking. Taken together, enhanced oligodendroglia-neuroinflammatory response during abstinence may contribute to brain trauma in chronic alcohol drinking subjects and be a risk factor for enhanced propensity for alcohol relapse. PMID:27542327

Current status and future R&D for reduced-activation ferritic/martensitic steels

NASA Astrophysics Data System (ADS)

Hishinuma, A.; Kohyama, A.; Klueh, R. L.; Gelles, D. S.; Dietz, W.; Ehrlich, K.

1998-10-01

International research and development programs on reduced-activation ferritic/martensitic steels, the primary candidate-alloys for a DEMO fusion reactor and beyond, are briefly summarized, along with some information on conventional steels. An International Energy Agency (IEA) collaborative test program to determine the feasibility of reduced-activation ferritic/martensitic steels for fusion is in progress and will be completed within this century. Baseline properties including typical irradiation behavior for Fe-(7-9)%Cr reduced-activation ferritic steels are shown. Most of the data are for a heat of modified F82H steel, purchased for the IEA program. Experimental plans to explore possible problems and solutions for fusion devices using ferromagnetic materials are introduced. The preliminary results show that it should be possible to use a ferromagnetic vacuum vessel in tokamak devices.

Strong variable linear polarization in the cool active star II Peg

NASA Astrophysics Data System (ADS)

Rosén, Lisa; Kochukhov, Oleg; Wade, Gregg A.

2014-08-01

Magnetic fields of cool active stars are currently studied polarimetrically using only circular polarization observations. This provides limited information about the magnetic field geometry since circular polarization is only sensitive to the line-of-sight component of the magnetic field. Reconstructions of the magnetic field topology will therefore not be completely trustworthy when only circular polarization is used. On the other hand, linear polarization is sensitive to the transverse component of the magnetic field. By including linear polarization in the reconstruction the quality of the reconstructed magnetic map is dramatically improved. For that reason, we wanted to identify cool stars for which linear polarization could be detected at a level sufficient for magnetic imaging. Four active RS CVn binaries, II Peg, HR 1099, IM Peg, and σ Gem were observed with the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. Mean polarization profiles in all four Stokes parameters were derived using the multi-line technique of least-squares deconvolution (LSD). Not only was linear polarization successfully detected in all four stars in at least one observation, but also, II Peg showed an extraordinarily strong linear polarization signature throughout all observations. This qualifies II Peg as the first promising target for magnetic Doppler imaging in all four Stokes parameters and, at the same time, suggests that other such targets can possibly be identified.

How to reduce injuries to residual trees during stand management activities.

Treesearch

Paul E. Aho; Gary Fiddler; Gregory M. Filip

1983-01-01

Losses of trees and tree volume that result from decay initiated by mechanical injuries during stand management activities in the western United States are substantial. They can be reduced through improved logging methods and careful planning of other forest management activities.

Design of novel potent antihyperlipidemic agents with antioxidant/anti-inflammatory properties: exploiting phenothiazine's strong antioxidant activity.

PubMed

Matralis, Alexios N; Kourounakis, Angeliki P

2014-03-27

Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis.

Reduced salience and default mode network activity in women with anorexia nervosa

PubMed Central

McFadden, Kristina L.; Tregellas, Jason R.; Shott, Megan E.; Frank, Guido K.W.

2014-01-01

Background The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated. Methods Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis. Results We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate–corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN. Limitations Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates. Conclusion Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach

Strong Libraries, Strong Scores

ERIC Educational Resources Information Center

Gray, Carlyn

2006-01-01

This article talks about the first-ever Texas Conference on School Libraries on April 6, 2005 that was attended by one hundred thirty-five school administrators and trustees. The miniconference, entitled Strong Libraries, Strong Scores, was held at the Austin Hilton, Austin, Texas during the Texas Library Association's Annual Conference and was…

PPAR{gamma} agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

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

Lee, Seong-Ryong; Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Taegu; Kim, Hahn-Young

2009-02-27

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation withmore » pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.« less

Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

PubMed Central

Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

2015-01-01

Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

Noise Mitigation During Pile Driving Efficiently Reduces Disturbance of Marine Mammals.

PubMed

Nehls, Georg; Rose, Armin; Diederichs, Ansgar; Bellmann, Michael; Pehlke, Hendrik

2016-01-01

Acoustic monitoring of harbor porpoises (Phocoena phocoena L., 1758) indicated a strongly reduced disturbance by noise emitted by pile driving for offshore wind turbine foundations insulated by a big bubble curtain (BBC). This newly developed noise mitigation system was tested during construction of the offshore wind farm Borkum West II (North Sea). Because porpoise activity strongly corresponded to the sound level, operation of the new system under its most suitable configuration reduced the porpoise disturbance area by ~90%. Hence, for the first time, a positive effect of a noise mitigation system during offshore pile driving on an affected marine mammal species could be demonstrated.

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury

PubMed Central

Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A.; Carlton, Susan M.; Walters, Edgar T.

2017-01-01

Abstract A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration–approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects. PMID:28073317

Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

PubMed

Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

2017-03-15

A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

PubMed Central

Luechinger, Roger; Boesiger, Peter; Rasch, Björn

2013-01-01

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

Oxytocin reduces amygdala activity, increases social interactions and reduces anxiety-like behavior irrespective of NMDAR antagonism

PubMed Central

Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E.; Siegel, Steven J.

2015-01-01

Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala leading to increased fear and social anxiety. Several studies have demonstrated the pro-social effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of sub-chronic oxytocin on electroencephalographic (EEG) activity in amygdala of mice during performance of the three chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine, but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, while oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate pro-social and social anxiety pathways may mediate social preference. PMID:26214213

Novel orthodontic cement containing dimethylaminohexadecyl methacrylate with strong antibacterial capability.

PubMed

Feng, Xiaodong; Zhang, Ning; Xu, Hockin H K; Weir, Michael D; Melo, Mary Anne S; Bai, Yuxing; Zhang, Ke

2017-09-26

Orthodontic treatments increase the incidence of white spot lesions. The objectives of this study were to develop an antibacterial orthodontic cement to inhibit demineralization, and to evaluate its enamel shear bond strength and anti-biofilm properties. Novel antibacterial monomer dimethylaminohexadecyl methacrylate (DMAHDM) was synthesized and incorporated into Transbond XT at 0, 1.5 and 3% by mass. Anti-biofilm activity was assessed using a human dental plaque microcosm biofilm model. Shear bond strength and adhesive remnant index were also tested. Biofilm activity precipitously dropped when contacting orthodontic cement with DMAHDM. Orthodontic cement containing 3% DMAHDM significantly reduced biofilm metabolic activity and lactic acid production (p<0.05), and decreased biofilm colony-forming unit (CFU) by two log. Water-aging for 90 days had no adverse influence on enamel shear bond strength (p>0.1). By incorporating DMAHDM into Transbond XT for the first time, the modified orthodontic cement obtained a strong antibacterial capability without compromising the enamel bond strength.

Antenna gain of actively compensated free-space optical communication systems under strong turbulence conditions.

PubMed

Juarez, Juan C; Brown, David M; Young, David W

2014-05-19

Current Strehl ratio models for actively compensated free-space optical communications terminals do not accurately predict system performance under strong turbulence conditions as they are based on weak turbulence theory. For evaluation of compensated systems, we present an approach for simulating the Strehl ratio with both low-order (tip/tilt) and higher-order (adaptive optics) correction. Our simulation results are then compared to the published models and their range of turbulence validity is assessed. Finally, we propose a new Strehl ratio model and antenna gain equation that are valid for general turbulence conditions independent of the degree of compensation.

Fit and Strong!: bolstering maintenance of physical activity among older adults with lower-extremity osteoarthritis.

PubMed

Hughes, Susan L; Seymour, Rachel B; Campbell, Richard T; Desai, Pankaja; Huber, Gail; Chang, H Justina

2010-01-01

To compare the impact of negotiated vs. mainstreamed follow-up with telephone reinforcement (TR) on maintenance of physical activity (PA) after Fit and Strong! ended. A multisite comparative effectiveness trial with repeated measures. Single group random effects analyses showed significant improvements at 2, 6, 12, and 18 months on PA maintenance, lower-extremity (LE) pain and stiffness, LE function, sit-stand, 6-minute distance walk, and anxiety/depression. Analyses by follow-up condition showed persons in the negotiated with TR group maintained a 21% increase in caloric expenditures over baseline at 18 months, with lesser benefits seen in the negotiated-only, mainstreamed-with-TR, and mainstreamed-only groups. Significant benefits of telephone dose were also seen on LE joint stiffness, pain, and function as well as anxiety and anxiety/depression. The negotiated follow-up contract that Fit and Strong! uses, bolstered by TR, is associated with enhanced long-term PA maintenance and health outcomes.

[Curcumine inhibits migration and invasion of hepatic stellate cells by reducing MMP-2 expression and activity].

PubMed

Huang, Jian-xian; Zhu, Bao-he; He, De; Huang, Lin; Hu, Ke; Huang, Bo

2009-11-01

To investigate the molecular mechanism of the inhibitory effect of curcumine on the migration and invasion of hepatic stellate cells (HSC). Rat hepatic stellate cells were cultured and activated with ConA. Matrix metalloproteinase-2 (MMP-2) expression and activity was determined by Western blot and gelatin zymography. Migration and invasion of HSC was assessed by wound healing assay and modified Boyden chamber assay. Curcumine reduced the level and activity of MMP-2 expression in activated HSC in a dose-dependent manner. When treated with 25, 50 or 100 micromol/L curcumine, the expression of MMP-2 was reduced by 21.8%+/-5.1%, 65.5%+/-9.2% or 87.9%+/-11.5% (P < 0.05), and the activity of MMP-2 was also significantly reduced by curcumine. Migration and invasion of activated HSC was also inhibited by curcumine in a dose-dependent way. When treated with 25, 50 or 100 micromol/L curcumine, the migration of activated HSC was reduced by 27.5%+/-5.8%, 54.4%+/-7.6% or 67.1%+/-9.3% (P < 0.05), and the invasion of activated HSC was also significantly reduced by curcumine. Curcumine inhibits migration and invasion of activated HSC by reducing MMP-2 expression and activity.

Large roads reduce bat activity across multiple species.

PubMed

Kitzes, Justin; Merenlender, Adina

2014-01-01

Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations.

Strongly correlated perovskite fuel cells

DOE PAGES

Zhou, You; Guan, Xiaofei; Zhou, Hua; ...

2016-05-16

Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes.more » Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.« less

Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

PubMed

DeSmet, Marsha L; Fleet, James C

2017-10-01

High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH) 2 D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH) 2 D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH) 2 D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH) 2 D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

PubMed

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-07-01

Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Implementing "Strong Kids" School-Wide to Reduce Internalizing Behaviors and Increase Prosocial Behaviors

ERIC Educational Resources Information Center

Kramer, Thomas J.; Caldarella, Paul; Young, K. Richard; Fischer, Lane; Warren, Jared S.

2014-01-01

Instruction and training in social and emotional learning (SEL) is an important component in addressing the emotional and behavioral needs of students. This study is the first to examine whether "Strong Kids", an SEL program, delivered school-wide in all classrooms, could result in decreased internalizing behaviors and increased…

Solid strong base K-Pt/NaY zeolite nano-catalytic system for completed elimination of formaldehyde at room temperature

NASA Astrophysics Data System (ADS)

Song, Shaoqing; Wu, Xi; Lu, Changhai; Wen, Meicheng; Le, Zhanggao; Jiang, Shujuan

2018-06-01

Solid strong base nano-catalytic system of K-modification NaY zeolite supported 0.08% Pt (K-Pt/NaY) were constructed for eliminating HCHO at room temperature. In the catalytic process, activation energy over K-Pt/NaY nano-catalytic system was greatly decreased along with the enhanced reaction rate. Characterization and catalytic tests revealed the surface electron structure of K-Pt/NaY was improved, as reflected by the enhanced HCHO adsorption capability, high sbnd OH concentration, and low-temperature reducibility. Therefore, the optimal K-Pt/NaY showed high catalytic efficiency and strong H2O tolerance for HCHO elimination by directly promoting the reaction between active sbnd OH and formate species. These results may suggest a new way for probing the advanced solid strong base nano-catalytic system for the catalytic elimination of indoor HCHO.

Can Graduated Compressive Stockings Reduce Muscle Activity during Running?

ERIC Educational Resources Information Center

Lucas-Cuevas, Ángel Gabriel; Priego Quesada, José Ignacio; Giménez, José Vicente; Aparicio, Inmaculada; Cortell-Tormo, Juan Manuel; Pérez-Soriano, Pedro

2017-01-01

Purpose: Graduated compressive stockings (GCS) have been suggested to influence performance by reducing muscle oscillations and improving muscle function and efficiency. However, no study to date has analyzed the influence of GCS on muscle activity during running. The objective of the study was to analyze the influence of GCS on the perception of…

Reward Size Informs Repeat-Switch Decisions and Strongly Modulates the Activity of Neurons in Parietal Cortex

PubMed Central

Kubanek, Jan; Snyder, Lawrence H.

2017-01-01

Abstract Behavior is guided by previous experience. Good, positive outcomes drive a repetition of a previous behavior or choice, whereas poor or bad outcomes lead to an avoidance. How these basic drives are implemented by the brain has been of primary interest to psychology and neuroscience. We engaged animals in a choice task in which the size of a reward outcome strongly governed the animals' subsequent decision whether to repeat or switch the previous choice. We recorded the discharge activity of neurons implicated in reward-based choice in 2 regions of parietal cortex. We found that the tendency to retain previous choice following a large (small) reward was paralleled by a marked decrease (increase) in the activity of parietal neurons. This neural effect is independent of, and of sign opposite to, value-based modulations reported in parietal cortex previously. This effect shares the same basic properties with signals previously reported in the limbic system that detect the size of the recently obtained reward to mediate proper repeat-switch decisions. We conclude that the size of the obtained reward is a decision variable that guides the decision between retaining a choice or switching, and neurons in parietal cortex strongly respond to this novel decision variable. PMID:26491065

AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

PubMed

Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

2017-04-04

Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

A reduced energy supply strategy in active vibration control

NASA Astrophysics Data System (ADS)

Ichchou, M. N.; Loukil, T.; Bareille, O.; Chamberland, G.; Qiu, J.

2011-12-01

In this paper, a control strategy is presented and numerically tested. This strategy aims to achieve the potential performance of fully active systems with a reduced energy supply. These energy needs are expected to be comparable to the power demands of semi-active systems, while system performance is intended to be comparable to that of a fully active configuration. The underlying strategy is called 'global semi-active control'. This control approach results from an energy investigation based on management of the optimal control process. Energy management encompasses storage and convenient restitution. The proposed strategy monitors a given active law without any external energy supply by considering purely dissipative and energy-demanding phases. Such a control law is offered here along with an analysis of its properties. A suboptimal form, well adapted for practical implementation steps, is also given. Moreover, a number of numerical experiments are proposed in order to validate test findings.

Physical activity is Associated with Reduced Fatigue in Adults Living with HIV/AIDS

PubMed Central

Perazzo, Joe; Decker, Michael; Horvat-Davey, Christine; Sattar, Abdus; Voss, Joachim

2016-01-01

Aims To describe the relationships among home-based physical activity, fatigue, sleep, gender and quality of life in people living with HIV/AIDS Background Fatigue is a common and distressing symptom among people living with HIV/AIDS. Few interventions exist that effectively reduce fatigue in this population. Physical activity has shown promise to reduce fatigue in other populations, but its impact on fatigue in HIV/AIDS has not yet been explored. Design This study was conducted using a prospective, descriptive cohort design. Methods Overall, 90 adults living with HIV/AIDS completed cross-sectional measures. Home-based physical activity was measured using a seven-day self-report diary. Fatigue was measured using the self-reported HIV-Related Fatigue Scale. Sleep was assessed using wrist actigraphy and quality of life was assessed using the HIV-Associated Quality of Life Scale. Data were collected from December 2012 – April 2013 and analyzed using correlations and multiple linear regression. Results The number of minutes of home-based physical activity was significantly associated with reduced fatigue among people living with HIV/AIDS. Additionally, increased fatigue was associated with decreased quality of life. No associations were found among fatigue, sleep or gender. Conclusions Our study demonstrates that physical activity in the home setting is an effective strategy to reduce fatigue among people living with HIV/AIDS. Future work developing and testing interventions to improve home-based physical activity in this population is needed. PMID:27485463

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

PubMed

Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

2010-10-01

PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

Men without a sense of smell exhibit a strongly reduced number of sexual relationships, women exhibit reduced partnership security - a reanalysis of previously published data.

PubMed

Croy, Ilona; Bojanowski, Viola; Hummel, Thomas

2013-02-01

Olfactory function influences social behavior. For instance, olfaction seems to play a key role in mate choice and helps detecting emotions in other people. In a previous study, we showed that people who were born without a sense of smell exhibit enhanced social insecurity. Based on the comments to this article we decided to have a closer look to whether the absence of the sense of smell affects men and women differently. Under this focus questionnaire data of 32 patients, diagnosed with isolated congenital anosmia (10 men, 22 women) and 36 age-matched healthy controls (15 men, 21 women) was reanalyzed. In result, men and women without a sense of smell reported enhanced social insecurity, but with different consequences: Men who were born without a sense of smell exhibit a strongly reduced number of sexual relationships and women are affected such that they feel less secure about their partner. This emphasizes the importance of the sense of smell for intimate relationships. Copyright © 2012 Elsevier B.V. All rights reserved.

Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

PubMed Central

Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Dhar, Deepanshi; Panigrahi, Gati K.; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P.; Oberlies, Nicholas H.; Agarwal, Rajesh

2016-01-01

Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47phox). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. PMID:26979487

Structured Free-Play to Reduce Disruptive Activity Changes in a Head Start Classroom.

ERIC Educational Resources Information Center

Stollar, Stephanie A.; And Others

1994-01-01

Developed intervention to decrease number of inappropriate activity changes in Head Start classroom. Measurement of rate of activity changes was taken for two target children and comparison children. Intervention was able to reduce inappropriate activity changes by adding relatively unobtrusive classroom structure to activities. (Author/NB)

A New Sugarcane Cystatin Strongly Binds to Dental Enamel and Reduces Erosion.

PubMed

Santiago, A C; Khan, Z N; Miguel, M C; Gironda, C C; Soares-Costa, A; Pelá, V T; Leite, A L; Edwardson, J M; Buzalaf, M A R; Henrique-Silva, F

2017-08-01

Cystatin B was recently identified as an acid-resistant protein in acquired enamel pellicle; it could therefore be included in oral products to protect against caries and erosion. However, human recombinant cystatin is very expensive, and alternatives to its use are necessary. Phytocystatins are reversible inhibitors of cysteine peptidases that are found naturally in plants. In plants, they have several biological and physiological functions, such as the regulation of endogenous processes, defense against pathogens, and response to abiotic stress. Previous studies performed by our research group have reported high inhibitory activity and potential agricultural and medical applications of several sugarcane cystatins, including CaneCPI-1, CaneCPI-2, CaneCPI-3, and CaneCPI-4. In the present study, we report the characterization of a novel sugarcane cystatin, named CaneCPI-5. This cystatin was efficiently expressed in Escherichia coli, and inhibitory assays demonstrated that it was a potent inhibitor of human cathepsins B, K, and L ( K i = 6.87, 0.49, and 0.34 nM, respectively). The ability of CaneCPI-5 to bind to dental enamel was evaluated using atomic force microscopy. Its capacity to protect against initial enamel erosion was also tested in vitro via changes in surface hardness. CaneCPI-5 showed a very large force of interaction with enamel (e.g., compared with mucin and casein) and significantly reduced initial enamel erosion. These results suggest that the inclusion of CaneCPIs in dental products might confer protection against enamel erosion.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

PubMed

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy

PubMed Central

Mucsi, Ashley D.; Meng, Junchen; Yan, Jiacong; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D.; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W.

2017-01-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner. PMID:28082358

Strong and Long Makes Short: Strong-Pump Strong-Probe Spectroscopy.

PubMed

Gelin, Maxim F; Egorova, Dassia; Domcke, Wolfgang

2011-01-20

We propose a new time-domain spectroscopic technique that is based on strong pump and probe pulses. The strong-pump strong-probe (SPSP) technique provides temporal resolution that is not limited by the durations of the pump and probe pulses. By numerically exact simulations of SPSP signals for a multilevel vibronic model, we show that the SPSP signals exhibit electronic and vibrational beatings on time scales which are significantly shorter than the pulse durations. This suggests the possible application of SPSP spectroscopy for the real-time investigation of molecular processes that cannot be temporally resolved by pump-probe spectroscopy with weak pump and probe pulses.

Reducing vibration transfer from power plants by active methods

NASA Astrophysics Data System (ADS)

Kiryukhin, A. V.; Milman, O. O.; Ptakhin, A. V.

2017-12-01

The possibility of applying the methods of active damping of vibration and pressure pulsations for reducing their transfer from power plants into the environment, the seating, and the industrial premises are considered. The results of experimental works implemented by the authors on the active broadband damping of vibration and dynamic forces after shock-absorption up to 15 dB in the frequency band up to 150 Hz, of water pressure pulsations in the pipeline up to 20 dB in the frequency band up to 600 Hz, and of spatial low-frequency air noise indoors of a diesel generator at discrete frequency up to 20 dB are presented. It is shown that a reduction of vibration transfer through a vibration-isolating junction (expansion joints) of pipelines with liquid is the most complicated and has hardly been developed so far. This problem is essential for vibration isolation of power equipment from the seating and the environment through pipelines with water and steam in the power and transport engineering, shipbuilding, and in oil and gas pipelines in pumping stations. For improving efficiency, reducing the energy consumption, and decreasing the overall dimensions of equipment, it is advisable to combine the work of an active system with passive damping means, the use of which is not always sufficient. The executive component of the systems of active damping should be placed behind the vibration isolators (expansion joints). It is shown that the existence of working medium and connection of vibration with pressure pulsations in existing designs of pipeline expansion joints lead to growth of vibration stiffness of the expansion joint with the environment by two and more orders as compared with the static stiffness and makes difficulties for using the active methods. For active damping of vibration transfer through expansion joints of pipelines with a liquid, it is necessary to develop expansion joint structures with minimal connection of vibrations and pulsations and minimal

Reduced superoxide dismutase activity in xeroderma pigmentosum fibroblasts

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

Nishigori, C.; Miyachi, Y.; Imamura, S.

1989-10-01

This study was performed in order to assess the possible protective effect of superoxide dismutase (SOD) on ultraviolet (UV) damage in xeroderma pigmentosum (XP) fibroblasts. SOD activity in fibroblasts originating from seven xeroderma pigmentosum (XP) patients was significantly lower than that in normal cells (p less than 0.005). Average SOD activity in XP cells belonging to complementation group A was 3.68 +/- 0.54 (n = 7) and that in normal human cells was 5.79 +/- 1.59 (n = 6). Addition of SOD before and during UV irradiation (UVB and UVC) to the cells caused no change in the amount ofmore » unscheduled DNA synthesis and UV survival. A possible involvement of reduced SOD in XP and a possible protective effect by SOD on UV damage is discussed.« less

Exploring the optical contrast effect in strong atomic lines for exoplanets transiting active stars

NASA Astrophysics Data System (ADS)

Cauley, Paul W.; Redfield, Seth

2017-01-01

Transmission spectroscopy is a powerful tool for detecting and characterizing planetary atmospheres. Non-photospheric features on the stellar disk, however, can contaminate the planetary signal: during transit the observed spectrum is weighted towards the features not currently being occulted by the planet. This contrast effect can mimic absorption in the planetary atmosphere for strong atomic lines such as Na I, Ca II, and the hydrogen Balmer lines. While the contrast effect is negligible for quiet stars, contributions to the transmission signal from active stellar surfaces can produce ~1% changes in the line core. It is therefore critical that these contrast signals be differentiated from true absorption features in the planetary atmosphere. Here we present our work on simulating the contrast effect for an active stellar surface. We discuss the particular case of HD 189733 b, a well-studied hot Jupiter orbiting an active K-dwarf, due to the plethora of atomic absorption signals reported in its atmosphere.Specifically, we focus on Hα to address recent suggestions that the measured in-transit signals are a result of stellar activity. In the contrast model we include center-to-limb variations and calculate limb darkening parameters as a function of wavelength across the line of interest. The model includes contributions to the spectrum from spots, faculae and plages, filaments, and the bare stellar photosphere. Stellar rotation is also included. We find that it is very difficult to reproduce the measured in-transit Hα signals for reasonable active region parameters. In addition, it is difficult to create an in-transit contrast signature that lasts for the duration of the transit unless the planet is crossing an active latitudinal belt and is always obscuring active regions. This suggests that the Hα measurements arise predominantly in the planetary atmosphere. However, the contrast effect likely contributes to these signals. Furthermore, our results could be

A polysaccharide from Armillaria mellea exhibits strong in vitro anticancer activity via apoptosis-involved mechanisms.

PubMed

Wu, Jun; Zhou, Jinxu; Lang, Yaoguo; Yao, Lei; Xu, Hai; Shi, Hubo; Xu, Shidong

2012-11-01

Armillaria mellea is a famous traditional Chinese medicinal and edible fungus. In this study, we purified a water-soluble polysaccharide (AMP) from the fruiting bodies of this fungus. AMP contained 94.8% carbohydrate, 2.3% uronic acid and 0.5% protein. Its molecular weight was determined as 4.6 × 10⁵ Da, as determined by high-performance gel-permeation chromatography (HPGPC). Gas chromatography (GC) analysis indicated that AMP was mainly composed of d-glucose. In vitro assay, AMP exhibited a potent tumor growth inhibitory effect on A549 cells, and induced cell cycle disruption in the G0/G1 phase, accompanied by an increment of apoptotic cells. Furthermore, AMP induced the disruption of mitochondrial membrane potential, thus leading to cytochrome c release from mitochondria and activation of caspase-3 and -9. Taken together, our results demonstrate that AMP possesses strong antitumor activities through the mitochondria dependent pathway and activation of caspase cascade through cytochrome c release. Copyright © 2012 Elsevier B.V. All rights reserved.

Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion

PubMed Central

Luethi, Matthias S.; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

2016-01-01

Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. PMID:27217108

Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

PubMed Central

Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

2014-01-01

Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

A dental stool with chest support reduces lower back muscle activation.

PubMed

Tran, Viet; Turner, Reid; MacFadden, Andrew; Cornish, Stephen M; Esliger, Dale; Komiyama, Kunio; Chilibeck, Philip D

2016-09-01

Activation of back musculature during work tasks leads to fatigue and potential injury. This is especially prevalent in dentists who perform much of their work from a seated position. We examined the use of an ergonomic dental stool with mid-sternum chest support for reducing lower back muscle activation. Electromyography of lower back extensors was assessed from 30 dental students for 20 s during three conditions in random order: (a) sitting upright at 90° of hip flexion on a standard stool, (b) leaning forward at 80° of hip flexion on a standard stool, and (c) leaning forward at 80° of hip flexion while sitting on an ergonomic stool. Muscular activity of the back extensors was reduced when using the ergonomic stool compared to the standard stool, by 33-50% (p < 0.01). This suggests a potential musculoskeletal benefit with use of a dental stool with mid-sternum chest support.

Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

PubMed Central

Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

2016-01-01

Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

Impaired hippocampal glucose metabolism during and after flurothyl-induced seizures in mice: Reduced phosphorylation coincides with reduced activity of pyruvate dehydrogenase.

PubMed

McDonald, Tanya S; Borges, Karin

2017-07-01

To determine changes in glucose metabolism and the enzymes involved in the hippocampus ictally and postictally in the acute mouse flurothyl seizure model. [U- 13 C]-Glucose was injected (i.p.) prior to, or following a 5 min flurothyl-induced seizure. Fifteen minutes later, mice were killed and the total metabolite levels and % 13 C enrichment were analyzed in the hippocampal formation using gas chromatography-mass spectrometry. Activities of key metabolic and antioxidant enzymes and the phosphorylation status of pyruvate dehydrogenase were measured, along with lipid peroxidation. During seizures, total lactate levels increased 1.7-fold; however, [M + 3] enrichment of both lactate and alanine were reduced by 30% and 43%, respectively, along with a 28% decrease in phosphofructokinase activity. Postictally the % 13 C enrichments of all measured tricarboxylic acid (TCA) cycle intermediates and the amino acids were reduced by 46-93%. At this time, pyruvate dehydrogenase (PDH) activity was 56% of that measured in controls, and there was a 1.9-fold increase in the phosphorylation of PDH at ser232. Phosphorylation of PDH is known to decrease its activity. Here, we show that the increase of lactate levels during flurothyl seizures is from a source other than [U- 13 C]-glucose, such as glycogen. Surprisingly, although we saw a reduction in phosphofructokinase activity during the seizure, metabolism of [U- 13 C]-glucose into the TCA cycle seemed unaffected. Similar to our recent findings in the chronic phase of the pilocarpine model, postictally the metabolism of glucose by glycolysis and the TCA cycle was impaired along with reduced PDH activity. Although this decrease in activity may be a protective mechanism to reduce oxidative stress, which is observed in the flurothyl model, ATP is critical to the recovery of ion and neurotransmitter balance and return to normal brain function. Thus we identified promising novel strategies to enhance energy metabolism and recovery from

Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1.

PubMed

Wu, Bing; Yu, Lu; Wang, Yishi; Wang, Hongtao; Li, Chen; Yin, Yue; Yang, Jingrun; Wang, Zhifa; Zheng, Qiangsun; Ma, Heng

2016-01-19

Cardiac aging is characterized by accumulation of damaged proteins and decline of autophagic efficiency. Here, by forestalling SIRT1 carbonylated inactivation in aged heart, we determined the benefits of activation of aldehyde dehydrogenase 2 (ALDH2) on the autophagy. In this study, the ALDH2 KO mice progressively developed age-related heart dysfunction and showed reduction in the life span, which strongly suggests that ALDH2 ablation leads to cardiac aging. What's more, aged hearts displayed a significant decrease ALDH2 activity, resulting in accumulation of 4-HNE-protein adducts and protein carbonyls, impairment in the autophagy flux, and, consequently, deteriorated cardiac function after starvation. Sustained Alda-1 (selective ALDH2 activator) treatment increased cardiac ALDH2 activity and abrogated these effects. Using SIRT1 deficient heterozygous (Sirt1+/-) mice, we found that SIRT1 was necessary for ALDH2 activation-induced autophagy. We further demonstrated that ALDH2 activation attenuated SIRT1 carbonylation and improved SIRT1 activity, thereby increasing the deacetylation of nuclear LC3 and FoxO1. Sequentially, ALDH2 enhanced SIRT1 regulates LC3-Atg7 interaction and FoxO1 increased Rab7 expression, which were both necessary and sufficient for restoring autophagy flux. These results highlight that both accumulation of proteotoxic carbonyl stress linkage with autophagy decline contribute to heart senescence. ALDH2 activation is adequate to improve the autophagy flux by reducing the carbonyl modification on SIRT1, which in turn plays an important role in maintaining cardiac health during aging.

Ligand-accelerated activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI)-nitrido complex.

PubMed

Man, Wai-Lun; Lam, William W Y; Kwong, Hoi-Ki; Yiu, Shek-Man; Lau, Tai-Chu

2012-09-03

Kinetic and mechanistic studies on the intermolecular activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI) nitride were performed. The initial, rate-limiting step, the hydrogen atom transfer (HAT) from the alkane to Ru(VI)≡N, generates Ru(V)=NH and RC·HCH(2)R. The following steps involve N-rebound and desaturation. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cosmological Studies with Galaxy Clusters, Active Galactic Nuclei, and Strongly Lensed Quasars

NASA Astrophysics Data System (ADS)

Rumbaugh, Nicholas Andrew

The large-scale structure (LSS) of the universe provides scientists with one of the best laboratories for studying Lambda Cold Dark Matter (LambdaCDM) cosmology. Especially at high redshift, we see increased rates of galaxy cluster and galaxy merging in LSS relative to the field, which is useful for studying the hierarchical merging predicted by LambdaCDM. The largest identified bound structures, superclusters, have not yet virialized. Despite the wide range of dynamical states of their constituent galaxies, groups, and clusters, they are all still actively evolving, providing an ideal laboratory in which to study cluster and galaxy evolution. In this dissertation, I present original research on several aspects of LSS and LambdaCDM cosmology. Three separate studies are included, each one focusing on a different aspect. In the first study, we use X-ray and optical observations from nine galaxy clusters at high redshift, some embedded in larger structures and some isolated, to study their evolutionary states. We extract X-ray gas temperatures and luminosities as well as optical velocity dispersions. These cluster properties are compared using low-redshift scaling relations. In addition, we employ several tests of substructure, using velocity histograms, Dressler-Shectman tests, and centroiding offsets. We conclude that two clusters out of our sample are most likely unrelaxed, and find support for deviations from self-similarity in the redshift evolution of the Lx-T relation. Our numerous complementary tests of the evolutionary state of clusters suggest potential under-estimations of systematic error in studies employing only a single such test. In the second study, we use multi-band imaging and spectroscopy to study active galactic nuclei (AGN) in high-redshift LSS. The AGN were identified using X-ray imaging and matched to optical catalogs that contained spectroscopic redshifts to identify members of the structures. AGN host galaxies tended to be associated with the

Chemically active reduced graphene oxide with tunable C/O ratios.

PubMed

Compton, Owen C; Jain, Bonny; Dikin, Dmitriy A; Abouimrane, Ali; Amine, Khalil; Nguyen, Sonbinh T

2011-06-28

Organic dispersions of graphene oxide can be thermally reduced in polar organic solvents under reflux conditions to afford electrically conductive, chemically active reduced graphene oxide (CARGO) with tunable C/O ratios, dependent on the boiling point of the solvent. The reductions are achieved after only 1 h of reflux, and the corresponding C/O ratios do not change upon further thermal treatment. Hydroxyl and carboxyl groups can be removed when the reflux is carried out above 155 °C, while epoxides are removable only when the temperature is higher than 200 °C. The increasing hydrophobic nature of CARGO, as its C/O ratio increases, improves the dispersibility of the nanosheets in a polystyrene matrix, in contrast to the aggregates formed with CARGO having lower C/O ratios. The excellent processability of the obtained CARGO dispersions is demonstrated via free-standing CARGO papers that exhibit tunable electrical conductivity/chemical activity and can be used as lithium-ion battery anodes with enhanced Coulombic efficiency.

Strong imploding shock - The representative curve

NASA Astrophysics Data System (ADS)

Mishkin, E. A.; Alejaldre, C.

1981-02-01

The representative curve of the ideal gas behind the front of a spherically or cylindrically asymmetric strong imploding shock is derived. The partial differential equations of mass, momentum and energy conservation are reduced to a set of ordinary differential equations by the method of quasi-separation of variables, following which the reduced pressure and density as functions of the radius with respect to the shock front are explicit functions of coordinates defining the phase plane of the self-similar solution. The curve in phase space representing the state of the imploded gas behind the shock front is shown to pass through the point where the reduced pressure is maximum, which is located somewhat behind the shock front and ahead of the tail of the shock.

Recycle Alaska: Reduce, Reuse, Recycle. Activities Handbook, Teacher's Guide, and Student Worksheets.

ERIC Educational Resources Information Center

Alaska State Dept. of Education, Juneau.

Recycling is a very important aspect of conserving the environment for future generations. This guide addresses the topic of litter prevention for the Alaskan environment and contains 42 activities. Activity topics covered include Natural Cycles, Human Interruption of Natural Cycles, Reduce, Reuse, Recycle and Recycled Classroom. Grade level,…

Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress.

PubMed

Liu, Shaobin; Zeng, Tingying Helen; Hofmann, Mario; Burcombe, Ehdi; Wei, Jun; Jiang, Rongrong; Kong, Jing; Chen, Yuan

2011-09-27

Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar concentration and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest average size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O(2)(•-)) induced reactive oxygen species (ROS) production is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidation capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidation stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We envision that physicochemical properties of graphene-based materials, such as density of functional groups, size, and conductivity, can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials. © 2011 American Chemical Society

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.

PubMed

Li, Baoli; Ni, Shuaishuai; Mao, Fei; Chen, Feifei; Liu, Yifu; Wei, Hanwen; Chen, Wenhua; Zhu, Jin; Lan, Lefu; Li, Jian

2018-01-11

CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC 50 = 0.02-10.5 nM), along with lower hERG inhibition (IC 50 > 30 μM, ∼10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.

Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

PubMed

Ceriello, A; Marchi, E; Barbanti, M; Milani, M R; Giugliano, D; Quatraro, A; Lefebvre, P

1990-04-01

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

PubMed

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Strong ground motion prediction applying dynamic rupture simulations for Beppu-Haneyama Active Fault Zone, southwestern Japan

NASA Astrophysics Data System (ADS)

Yoshimi, M.; Matsushima, S.; Ando, R.; Miyake, H.; Imanishi, K.; Hayashida, T.; Takenaka, H.; Suzuki, H.; Matsuyama, H.

2017-12-01

We conducted strong ground motion prediction for the active Beppu-Haneyama Fault zone (BHFZ), Kyushu island, southwestern Japan. Since the BHFZ runs through Oita and Beppy cities, strong ground motion as well as fault displacement may affect much to the cities.We constructed a 3-dimensional velocity structure of a sedimentary basin, Beppu bay basin, where the fault zone runs through and Oita and Beppu cities are located. Minimum shear wave velocity of the 3d model is 500 m/s. Additional 1-d structure is modeled for sites with softer sediment: holocene plain area. We observed, collected, and compiled data obtained from microtremor surveys, ground motion observations, boreholes etc. phase velocity and H/V ratio. Finer structure of the Oita Plain is modeled, as 250m-mesh model, with empirical relation among N-value, lithology, depth and Vs, using borehole data, then validated with the phase velocity data obtained by the dense microtremor array observation (Yoshimi et al., 2016).Synthetic ground motion has been calculated with a hybrid technique composed of a stochastic Green's function method (for HF wave), a 3D finite difference (LF wave) and 1D amplification calculation. Fault geometry has been determined based on reflection surveys and active fault map. The rake angles are calculated with a dynamic rupture simulation considering three fault segments under a stress filed estimated from source mechanism of earthquakes around the faults (Ando et al., JpGU-AGU2017). Fault parameters such as the average stress drop, a size of asperity etc. are determined based on an empirical relation proposed by Irikura and Miyake (2001). As a result, strong ground motion stronger than 100 cm/s is predicted in the hanging wall side of the Oita plain.This work is supported by the Comprehensive Research on the Beppu-Haneyama Fault Zone funded by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan.

Acutely Decreased Thermoregulatory Energy Expenditure or Decreased Activity Energy Expenditure Both Acutely Reduce Food Intake in Mice

PubMed Central

Kaiyala, Karl J.; Morton, Gregory J.; Thaler, Joshua P.; Meek, Thomas H.; Tylee, Tracy; Ogimoto, Kayoko; Wisse, Brent E.

2012-01-01

Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R2 = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure. PMID:22936977

Human Bile Reduces Antimicrobial Activity of Selected Antibiotics against Enterococcus faecalis and Escherichia coli In Vitro.

PubMed

Wulkersdorfer, Beatrix; Jaros, David; Eberl, Sabine; Poschner, Stefan; Jäger, Walter; Cosentini, Enrico; Zeitlinger, Markus; Schwameis, Richard

2017-08-01

It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant, and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilization of the bile fluid by gamma irradiation, its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM), and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller-Hinton broth (MHB) over 24 h. Bacterial counts (in CFU per milliliter after 24 h) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis , indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM, and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis This effect was strongest for TGC against the two strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail. Copyright © 2017 American Society for Microbiology.

Reduced African Easterly Wave Activity with Quadrupled CO 2 in the Superparameterized CESM

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

Hannah, Walter M.; Aiyyer, Anantha

African easterly wave (AEW) activity is examined in quadrupled CO 2 experiments with the superparameterized CESM (SP-CESM). The variance of 2–10-day filtered precipitation increases with warming over the West African monsoon region, suggesting increased AEW activity. The perturbation enstrophy budget is used to investigate the dynamic signature of AEW activity. The northern wave track becomes more active associated with enhanced baroclinicity, consistent with previous studies. The southern track exhibits a surprising reduction of wave activity associated with less frequent occurrence of weak waves and a slight increase in the occurrence of strong waves. These changes are connected to changes inmore » the profile of vortex stretching and tilting that can be understood as interconnected consequences of increased static stability from the lapse rate response, weak temperature gradient balance, and the fixed anvil temperature hypothesis.« less

Reduced African Easterly Wave Activity with Quadrupled CO 2 in the Superparameterized CESM

DOE PAGES

Hannah, Walter M.; Aiyyer, Anantha

2017-10-01

African easterly wave (AEW) activity is examined in quadrupled CO 2 experiments with the superparameterized CESM (SP-CESM). The variance of 2–10-day filtered precipitation increases with warming over the West African monsoon region, suggesting increased AEW activity. The perturbation enstrophy budget is used to investigate the dynamic signature of AEW activity. The northern wave track becomes more active associated with enhanced baroclinicity, consistent with previous studies. The southern track exhibits a surprising reduction of wave activity associated with less frequent occurrence of weak waves and a slight increase in the occurrence of strong waves. These changes are connected to changes inmore » the profile of vortex stretching and tilting that can be understood as interconnected consequences of increased static stability from the lapse rate response, weak temperature gradient balance, and the fixed anvil temperature hypothesis.« less

Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons.

PubMed

Han, P; Lucero, M T

2005-01-01

Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death.

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

PubMed

Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

2015-12-01

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Can an incentive-based intervention increase physical activity and reduce sitting among adults? the ACHIEVE (Active Choices IncEntiVE) feasibility study.

PubMed

Ball, Kylie; Hunter, Ruth F; Maple, Jaimie-Lee; Moodie, Marj; Salmon, Jo; Ong, Kok-Leong; Stephens, Lena D; Jackson, Michelle; Crawford, David

2017-03-21

Despite recent interest in the potential of incentivisation as a strategy for motivating healthier behaviors, little remains known about the effectiveness of incentives in promoting physical activity and reducing sedentary behavior, and improving associated health outcomes. This pre-post-test design study investigated the feasibility, appeal and effects of providing non-financial incentives for promoting increased physical activity, reduced sedentary time, and reduced body mass index (BMI) and blood pressure among inactive middle-aged adults. Inactive men (n = 36) and women (n = 46) aged 40-65 years were recruited via a not-for-profit insurance fund and participated in a 4 month pre-post design intervention. Baseline and post-intervention data were collected on self-reported physical activity and sitting time (IPAQ-Long), BMI and blood pressure. Participants were encouraged to increase physical activity to 150 mins/week and reduce sedentary behavior by 150 mins/week in progressive increments. Incentives included clothing, recipe books, store gift vouchers, and a chance to win one of four Apple iPad Mini devices. The incentive component of the intervention was supported by an initial motivational interview and text messaging to encourage participants and provide strategies to increase physical activity and reduce sedentary behaviors. Only two participants withdrew during the program, demonstrating the feasibility of recruiting and retaining inactive middle-aged participants. While two-thirds of the sample qualified for the easiest physical activity incentive (by demonstrating 100 mins physical activity/week or 100 mins reduced sitting time/week), only one third qualified for the most challenging incentive. Goals to reduce sitting appeared more challenging, with 43% of participants qualifying for the first incentive, but only 20% for the last incentive. More men than women qualified for most incentives. Mean leisure-time physical activity increased by 252

How strong was the 2015/2016 El Niño event?

NASA Astrophysics Data System (ADS)

Iskandar, Iskhaq; Lestari, DeniOkta; Utari, PutriAdia; Sari, QurniaWulan; Setiabudidaya, Dedi; Mardiansyah, Wijaya; Supardi; Rozirwan

2018-04-01

On the interannual timescale, the Indonesian climate is strongly influenced by a coupled ocean-atmosphere modes in the tropical Pacific Ocean. During a warm phase (El Niño event), negative sea surface temperature anomalies (SSTA) in the western tropical Pacific lead to suppress convection activities causing reduce precipitation over the maritime continent. The situation is reverse during the cold season(La Niña event). In this study, the evolution of 2015/2016 El Niño event is evaluated based on the collected data by the Tropical Atmosphere Ocean/Triangle Trans-Ocean Buoy Network (TAO/TRITON) buoys. The results show that the evolution of the event has started in boreal spring (April – May 2015). It came to thepeak in boreal fall/winter (October – December 2015). The event lasted until boreal spring before it terminated in April/May 2016. In addition, the intensity of the event is classified as a strong event, and it is one of the strongest El Niño events during the last three decades.

‘Sleepy’ inward rectifier channels in guinea-pig cardiomyocytes are activated only during strong hyperpolarization

PubMed Central

Liu, Gong Xin; Daut, Jürgen

2002-01-01

K+ channels of isolated guinea-pig cardiomyocytes were studied using the patch-clamp technique. At transmembrane potentials between −120 and −220 mV we observed inward currents through an apparently novel channel. The novel channel was strongly rectifying, no outward currents could be recorded. Between −200 and −160 mV it had a slope conductance of 42.8 ± 3.0 pS (s.d.; n = 96). The open probability (Po) showed a sigmoid voltage dependence and reached a maximum of 0.93 at −200 mV, half-maximal activation was approximately −150 mV. The voltage dependence of Po was not affected by application of 50 μm isoproterenol. The open-time distribution could be described by a single exponential function, the mean open time ranged between 73.5 ms at −220 mV and 1.4 ms at −160 mV. At least two exponential components were required to fit the closed time distribution. Experiments with different external Na+, K+ and Cl− concentrations suggested that the novel channel is K+ selective. Extracellular Ba2+ ions gave rise to a voltage-dependent reduction in Po by inducing long closed states; Cs+ markedly reduced mean open time at −200 mV. In cell-attached recordings the novel channel frequently converted to a classical inward rectifier channel, and vice versa. This conversion was not voltage dependent. After excision of the patch, the novel channel always converted to a classical inward rectifier channel within 0–3 min. This conversion was not affected by intracellular Mg2+, phosphatidylinositol (4,5)-bisphosphate or spermine. Taken together, our findings suggest that the novel K+ channel represents a different ‘mode’ of the classical inward rectifier channel in which opening occurs only at very negative potentials. PMID:11897847

Strong linkage between active microbial communities and microbial carbon usage in a deglaciated terrain of the High Arctic

NASA Astrophysics Data System (ADS)

Kim, M.; Gyeong, H. R.; Lee, Y. K.

2017-12-01

Soil microorganisms play pivotal roles in ecosystem development and carbon cycling in newly exposed glacier forelands. However, little is known about carbon utilization pattern by metabolically active microbes over the course of ecosystem succession in these nutrient-poor environments. We investigated RNA-based microbial community dynamics and its relation to microbial carbon usage along the chronosequence of a High Arctic glacier foreland. Among microbial taxa surveyed (bacteria, archaea and fungi), bacteria are among the most metabolically active taxa with a dominance of Cyanobacteria and Actinobacteria. There was a strong association between microbial carbon usage and active Actinobacterial communities, suggesting that member of Actinobacteria are actively involved in organic carbon degradation in glacier forelands. Both bacterial community and microbial carbon usage are converged towards later stage of succession, indicating that the composition of soil organic carbon plays important roles in structuring bacterial decomposer communities during ecosystem development.

[Physical activity as a factor reducing aggressive behaviour in adolescents in gymnasium school age].

PubMed

Rotter, Iwona; Kotwas, Artur; Kemicer-Chmielewska, Ewa; Watral, Aleksandra

Violence among adolescents is one of the most serious problems, and has significantly increased in recent years. Studies conducted in 2011 on aggression and violence in schools reported that the most widespread form of offence is verbal aggression. As many as 63% of students had experience of being ridiculed, humiliated or offended. According to research, 33% of students suffered from physical aggression (PA). The aim of the study to evaluate the relationship between physical activity and the incidence of aggressive behaviour in adolescents of lower -secondary school age. The study was conducted in autumn 2013, in West Pomerania province in Poland, among 807 students of a lower -secondary school. A diagnostic survey method with a standardized questionnaire (Aggression Questionnaire) by H. Buss and M. Perry of 1992 (Amity version) was used. Statistical analysis was performed in Statistica Pl version 10 using the Kruskal–Wallis test and the U Mann–Whitney test with a significance level of p ≤ 0.05. The Kruskal–Wallis test showed only a statistically significant difference between the groups surveyed in relation to the frequency of attendance at additional sports activities and the level of PA (p = 0.02). Subjects who engage in team sports show a higher tendency for physical aggression than those engaged in individual sports. Taking into account the higher level of PA in adolescents performing sport 3–4 times a week compared to physically inactive and very active adolescents (more than 5 times a week), it may be presumed that sport attracts people with high physical aggression tendencies. Only with strong involvement in sport is the level of aggression reduced. There is a need for research on the personality of young athletes, which would give credence to this thesis.

Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking.

PubMed

Augur, Isabel F; Wyckoff, Andrew R; Aston-Jones, Gary; Kalivas, Peter W; Peters, Jamie

2016-09-28

The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues. The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse-promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues. Copyright © 2016 the authors 0270-6474/16/3610174-07$15.00/0.

Active member vibration control experiment in a KC-135 reduced gravity environment

NASA Technical Reports Server (NTRS)

Lawrence, C. R.; Lurie, B. J.; Chen, G.-S.; Swanson, A. D.

1991-01-01

An active member vibration control experiment in a KC-135 reduced gravity environment was carried out by the Air Force Flight Dynamics Laboratory and the Jet Propulsion Laboratory. Two active members, consisting of piezoelectric actuators, displacement sensors, and load cells, were incorporated into a 12-meter, 104 kg box-type test structure. The active member control design involved the use of bridge (compound) feedback concept, in which the collocated force and velocity signals are feedback locally. An impact-type test was designed to accommodate the extremely short duration of the reduced gravity testing window in each parabolic flight. The moving block analysis technique was used to estimate the modal frequencies and dampings from the free-decay responses. A broadband damping performance was demonstrated up to the ninth mode of 40 Hz. The best damping performance achieved in the flight test was about 5 percent in the fourth mode of the test structure.

The facial massage reduced anxiety and negative mood status, and increased sympathetic nervous activity.

PubMed

Hatayama, Tomoko; Kitamura, Shingo; Tamura, Chihiro; Nagano, Mayumi; Ohnuki, Koichiro

2008-12-01

The aim of this study was to clarify the effects of 45 min of facial massage on the activity of autonomic nervous system, anxiety and mood in 32 healthy women. Autonomic nervous activity was assessed by heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, we evaluated the high-frequency components (HF) and the low- to high-frequency ratio (LF/HF ratio), reflecting parasympathetic nervous activity and sympathetic nervous activity, respectively. The State Trait Anxiety Inventory (STAI) and the Profile of Mood Status (POMS) were administered to evaluate psychological status. The score of STAI and negative scale of POMS were significantly reduced following the massage, and only the LF/HF ratio was significantly enhanced after the massage. It was concluded that the facial massage might refresh the subjects by reducing their psychological distress and activating the sympathetic nervous system.

Chemically engineered sulfated glucans from rice bran exert strong antiviral activity at the stage of viral entry.

PubMed

Ray, Bimalendu; Hutterer, Corina; Bandyopadhyay, Shruti S; Ghosh, Kanika; Chatterjee, Udipta R; Ray, Sayani; Zeitträger, Isabel; Wagner, Sabrina; Marschall, Manfred

2013-12-27

Attachment and entry of many viruses are mediated by their affinity for polysaccharides present on the surface of target cells. In this paper, we demonstrate that sulfated glucans isolated from rice (Oryza sativa) can be utilized as experimental drugs exerting strong antiviral activity. In particular, oleum-DMF-based extraction is described as a procedure for the generation of chemically engineered glucans from commercially available rice bran. The one-step procedure has the potential to provide a spectrum of related glucans with varying molecular masses and modifications, including sulfation. The sulfated glucans P444, P445, and P446 possess increased antiviral activity compared to a previously described glucan (S1G). P444, P445, and P446 were highly active against human cytomegalovirus (HCMV), moderately active against other members of the family Herpesviridae, while not active against unrelated viruses. Specific experimentation with HCMV-infected cells provided evidence that antiviral activity was based on inhibition of viral entry and that inhibition occurred in the absence of drug-induced cytotoxicity. These findings underline the high potential of sulfated glucans for antiviral research and drug development. In addition, the procedure described for the efficient transformation of glucan hydroxy groups to sulfate groups may be similarly beneficial for the chemical alteration of other natural products.

Lower physical activity is a strong predictor of cardiovascular events in elderly patients with type 2 diabetes mellitus beyond traditional risk factors: the Japanese Elderly Diabetes Intervention Trial.

PubMed

Iijima, Katsuya; Iimuro, Satoshi; Shinozaki, Tomohiro; Ohashi, Yasuo; Sakurai, Takashi; Umegaki, Hiroyuki; Araki, Atsushi; Ouchi, Yasuyoshi; Ito, Hideki

2012-04-01

It is well known that a decline in physical activity is associated with lifestyle-related diseases including cardiovascular (CV) events. However, little is known about the association between physical activity and CV events in elderly patients, because recent accumulating reports have mainly dealt with middle-aged populations. In this study, we investigated the correlation between physical activity and CV events in Japanese elderly patients with type 2 diabetes mellitus (T2DM). A total of 938 Japanese elderly patients with T2DM (447 men and 491 women, mean age 71.9 years) enrolled (2000-2002) in the Japanese Elderly Diabetes Intervention Trial (J-EDIT) were used in this study. Physical activity consisting of three components, work, sports and leisure-time, of their lifestyle was evaluated using the Baecke questionnaire at baseline. Total activity score (TAS) as a sum of each activity score was divided into four quartiles (Q1 to Q4). During a follow-up period of 65.2 months, 165 events and 71 deaths in total occurred. Higher TAS grade was associated with reduced risk of all events (hazard ratios: 0.82, 0.77 and 0.54 in Q2, Q3 and Q4, respectively) with statistical significance. Even after multivariate adjustment for covariates, higher TAS grade was a strong predictor of all events, and the prediction by TAS of cerebrovascular events was more effective than that of cardiac events. In contrast, all-cause mortality gradually decreased according to TAS grade; however, no statistical significance was found. Among the four grades of TAS, no significant change in several parameters, such as profiles of lipid and glucose metabolism, blood pressure, physical measurements, cognitive function and depression scale, was found throughout the follow-up period, suggesting that the higher level of physical activity itself was associated with the risk reduction of primary events. Lower physical activity is a strong and independent predictor of all CV events in the elderly with T2DM

A Test of the Active-Day Fraction Method of Sunspot Group Number Calibration: Dependence on the Level of Solar Activity

NASA Astrophysics Data System (ADS)

Willamo, T.; Usoskin, I. G.; Kovaltsov, G. A.

2018-04-01

The method of active-day fraction (ADF) was proposed recently to calibrate different solar observers to standard observational conditions. The result of the calibration may depend on the overall level of solar activity during the observational period. This dependency is studied quantitatively using data of the Royal Greenwich Observatory by formally calibrating synthetic pseudo-observers to the full reference dataset. It is shown that the sunspot group number is precisely estimated by the ADF method for periods of moderate activity, may be slightly underestimated by 0.5 - 1.5 groups ({≤} 10%) for strong and very strong activity, and is strongly overestimated by up to 2.5 groups ({≤} 30%) for weak-to-moderate activity. The ADF method becomes inapplicable for the periods of grand minima of activity. In general, the ADF method tends to overestimate the overall level of activity and to reduce the long-term trends.

Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.

PubMed

Mosconi, Lisa; de Leon, Mony; Murray, John; E, Lezi; Lu, Jianghua; Javier, Elizabeth; McHugh, Pauline; Swerdlow, Russell H

2011-01-01

Biomarker studies demonstrate inheritance of glucose hypometabolism and increased amyloid-β deposition in adult offspring of mothers, but not fathers, affected by late-onset Alzheimer's disease (LOAD). The underlying genetic mechanisms are unknown. We investigated whether cognitively normal (NL) individuals with a maternal history of LOAD (MH) have reduced platelet mitochondrial cytochrome oxidase activity (COX, electron transport chain complex IV) compared to those with paternal (PH) or negative family history (NH). Thirty-six consecutive NL individuals (age 55 ± 15 y, range 27-71 y, 56% female, CDR = 0, MMSE ≥28, 28% APOE-4 carriers), including 12 NH, 12 PH, and 12 MH, received a blood draw to measure platelet mitochondrial COX activity. Citrate synthase activity (CS) was measured as a reference. Groups were comparable for clinical and neuropsychological measures. We found that after correcting for CS, COX activity was reduced by 29% in MH compared to NH, and by 30% in MH compared to PH (p ≤ 0.006). Results remained significant controlling for age, gender, education, and APOE. No differences were found between PH and NH. COX measures discriminated MH from the other groups with accuracy ≥75%, and relative risk ≥3 (p ≤ 0.005). Among NL with LOAD-parents, only those with MH showed reduced COX activity in platelet mitochondria compared to PH and NH. The association between maternal history of LOAD and systemic COX reductions suggests transmission via mitochondrial DNA, which is exclusively maternally inherited in humans.

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

PubMed

Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

2017-02-15

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel technology to increase antioxidant activity of an antioxidant by reducing volatility

USDA-ARS?s Scientific Manuscript database

During frying, an antioxidant is lost by reaction with radicals for its antioxidant activity, but it is also lost by decomposition and evaporation before it is able to exert antioxidant activity. Some low molecular weight antioxidants are often so volatile that they show much reduced antioxidant act...

Active fans and grizzly bears: Reducing risks for wilderness campers

NASA Astrophysics Data System (ADS)

Sakals, M. E.; Wilford, D. J.; Wellwood, D. W.; MacDougall, S. A.

2010-03-01

Active geomorphic fans experience debris flows, debris floods and/or floods (hydrogeomorphic processes) that can be hazards to humans. Grizzly bears ( Ursus arctos) can also be a hazard to humans. This paper presents the results of a cross-disciplinary study that analyzed both hydrogeomorphic and grizzly bear hazards to wilderness campers on geomorphic fans along a popular hiking trail in Kluane National Park and Reserve in southwestern Yukon Territory, Canada. Based on the results, a method is proposed to reduce the risks to campers associated with camping on fans. The method includes both landscape and site scales and is based on easily understood and readily available information regarding weather, vegetation, stream bank conditions, and bear ecology and behaviour. Educating wilderness campers and providing a method of decision-making to reduce risk supports Parks Canada's public safety program; a program based on the principle of user self-sufficiency. Reducing grizzly bear-human conflicts complements the efforts of Parks Canada to ensure a healthy grizzly bear population.

Towards a high thermoelectric performance in rare-earth substituted SrTiO3: effects provided by strongly-reducing sintering conditions.

PubMed

Kovalevsky, A V; Yaremchenko, A A; Populoh, S; Thiel, P; Fagg, D P; Weidenkaff, A; Frade, J R

2014-12-28

Donor-substituted strontium titanate ceramics demonstrate one of the most promising performances among n-type oxide thermoelectrics. Here we report a marked improvement of the thermoelectric properties in rare-earth substituted titanates Sr0.9R0.1TiO3±δ (R = La, Ce, Pr, Nd, Sm, Gd, Dy, Y) to achieve maximal ZT values of as high as 0.42 at 1190 K < T < 1225 K, prepared via a conventional solid state route followed by sintering under strongly reducing conditions (10%H2-90%N2, 1773 K). As a result of complex defect chemistry, both electrical and thermal properties were found to be dependent on the nature of the rare-earth cation and exhibit an apparent correlation with the unit cell size. High power factors of 1350-1550 μW m(-1) K(-2) at 400-550 K were observed for R = Nd, Sm, Pr and Y, being among the largest reported so far for n-type conducting bulk-ceramic SrTiO3-based materials. Attractive ZT values at high temperatures arise primarily from low thermal conductivity, which, in turn, stem from effective phonon scattering in oxygen-deficient perovskite layers formed upon reduction. The results suggest that highly-reducing conditions are essential and should be employed, whenever possible, in other related micro/nanostructural engineering approaches to suppress the thermal conductivity in target titanate-based ceramics.

Finding Strong Bridges and Strong Articulation Points in Linear Time

NASA Astrophysics Data System (ADS)

Italiano, Giuseppe F.; Laura, Luigi; Santaroni, Federico

Given a directed graph G, an edge is a strong bridge if its removal increases the number of strongly connected components of G. Similarly, we say that a vertex is a strong articulation point if its removal increases the number of strongly connected components of G. In this paper, we present linear-time algorithms for computing all the strong bridges and all the strong articulation points of directed graphs, solving an open problem posed in [2].

A Forecast of Reduced Solar Activity and Its Implications for NASA

NASA Technical Reports Server (NTRS)

Schatten, Kenneth; Franz, Heather

2005-01-01

The "Solar Dynamo" method of solar activity forecasting is reviewed. Known generically as a 'precursor" method, insofar as it uses observations which precede solar activity generation, this method now uses the Solar Dynamo Amplitude (SODA) Index to estimate future long-term solar activity. The peak amplitude of the next solar cycle (#24), is estimated at roughly 124 in terms of smoothed F10.7 Radio Flux and 74 in terms of the older, more traditional smoothed international or Zurich Sunspot number (Ri or Rz). These values are significantly smaller than the amplitudes of recent solar cycles. Levels of activity stay large for about four years near the peak in smoothed activity, which is estimated to occur near the 2012 timeflame. Confidence is added to the prediction of low activity by numerous examinations of the Sun s weakened polar field. Direct measurements are obtained by the Mount Wilson Solar Observatory and the Wilcox Solar Observatory. Further support is obtained by examining the Sun s polar faculae (bright features), the shape of coronal soft X-ray "holes," and the shape of the "source surface" - a calculated coronal feature which maps the large scale structure of the Sun s field. These features do not show the characteristics of well-formed polar coronal holes associated with typical solar minima. They show stunted polar field levels, which are thought to result in stunted levels of solar activity during solar cycle #24. The reduced levels of solar activity would have concomitant effects upon the space environment in which satellites orbit. In particular, the largest influences would affect orbit determination of satellites in LEO (Low Earth Orbit), based upon the altered thermospheric and exospheric densities. A decrease in solar activity would result in smaller satellite decay rates, as well as fewer large solar events that can destroy satellite electronic functions. Other effects of reduced solar activity upon the space environment include enhanced

Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

PubMed

Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

2017-09-15

Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

Kinetics of Indigenous Nitrate Reducing Sulfide Oxidizing Activity in Microaerophilic Wastewater Biofilms

PubMed Central

Villahermosa, Desirée; Corzo, Alfonso; Garcia-Robledo, Emilio; González, Juan M.; Papaspyrou, Sokratis

2016-01-01

Nitrate decreases sulfide release in wastewater treatment plants (WWTP), but little is known on how it affects the microzonation and kinetics of related microbial processes within the biofilm. The effect of nitrate addition on these properties for sulfate reduction, sulfide oxidation, and oxygen respiration were studied with the use of microelectrodes in microaerophilic wastewater biofilms. Mass balance calaculations and community composition analysis were also performed. At basal WWTP conditions, the biofilm presented a double-layer system. The upper microaerophilic layer (~300 μm) showed low sulfide production (0.31 μmol cm-3 h-1) and oxygen consumption rates (0.01 μmol cm-3 h-1). The anoxic lower layer showed high sulfide production (2.7 μmol cm-3 h-1). Nitrate addition decreased net sulfide production rates, caused by an increase in sulfide oxidation rates (SOR) in the upper layer, rather than an inhibition of sulfate reducing bacteria (SRB). This suggests that the indigenous nitrate reducing-sulfide oxidizing bacteria (NR-SOB) were immediately activated by nitrate. The functional vertical structure of the biofilm changed to a triple-layer system, where the previously upper sulfide-producing layer in the absence of nitrate split into two new layers: 1) an upper sulfide-consuming layer, whose thickness is probably determined by the nitrate penetration depth within the biofilm, and 2) a middle layer producing sulfide at an even higher rate than in the absence of nitrate in some cases. Below these layers, the lower net sulfide-producing layer remained unaffected. Net SOR varied from 0.05 to 0.72 μmol cm-3 h-1 depending on nitrate and sulfate availability. Addition of low nitrate concentrations likely increased sulfate availability within the biofilm and resulted in an increase of both net sulfate reduction and net sulfide oxidation by overcoming sulfate diffusional limitation from the water phase and the strong coupling between SRB and NR-SOB syntrophic

An Assessment of Magnetic Conditions for Strong Coronal Heating in Solar Active Regions by Comparing Observed Loops with Computed Potential Field Lines

NASA Technical Reports Server (NTRS)

Gary, G. A.; Moore, R. L.; Porter, J. G.; Falconer, D. A.

1999-01-01

We report further results on the magnetic origins of coronal heating found from registering coronal images with photospheric vector magnetograms. For two complementary active regions, we use computed potential field lines to examine the global non-potentiality of bright extended coronal loops and the three-dimensional structure of the magnetic field at their feet, and assess the role of these magnetic conditions in the strong coronal heating in these loops. The two active regions are complementary, in that one is globally potential and the other is globally nonpotential, while each is predominantly bipolar, and each has an island of included polarity in its trailing polarity domain. We find the following: (1) The brightest main-arch loops of the globally potential active region are brighter than the brightest main- arch loops of the globally strongly nonpotential active region. (2) In each active region, only a few of the mainarch magnetic loops are strongly heated, and these are all rooted near the island. (3) The end of each main-arch bright loop apparently bifurcates above the island, so that it embraces the island and the magnetic null above the island. (4) At any one time, there are other main-arch magnetic loops that embrace the island in the same manner as do the bright loops but that are not selected for strong coronal heating. (5) There is continual microflaring in sheared core fields around the island, but the main-arch bright loops show little response to these microflares. From these observational and modeling results we draw the following conclusions: (1) The heating of the main-arch bright loops arises mainly from conditions at the island end of these loops and not from their global non-potentiality. (2) There is, at most, only a loose coupling between the coronal heating in the bright loops of the main arch and the coronal heating in the sheared core fields at their feet, although in both the heating is driven by conditions/events in and around the

Solid Waste Educational Resources and Activities: Let's Reduce, Reuse, and Recycle. [CD-ROM].

ERIC Educational Resources Information Center

Environmental Protection Agency, Washington, DC. Solid Waste and Emergency Response.

This contains games, activities, publications, and resources for students and teachers on how to reduce, reuse, recycle, and properly manage waste. It also contains a screen saver featuring runners-up from the Earth Day 2000 art contest. Activities and games include titles such as "Planet Protectors,""Recycle City,""Trash…

The strong UV source in the active E Galaxy NGC 4552

NASA Technical Reports Server (NTRS)

Oconnell, R. W.; Thuan, T. X.; Puschell, J. J.

1986-01-01

1200-3200 A IUE spectra of the nucleus of NGC 4552 (M89) were obtained in order to investigate the nature of the strong 10 micron source in this Galaxy. There is a strong, extended UV source in NGC 4552 which has a spatial distribution nearly identical with that at optical wavelengths and is undoubedly stellar in origin. Its properties are consistent with the correlation between UV source strength and metallicity pointed out by Faber (1983). There is no evidence for a nonthermal point source in the UV. It appears unlikely that the 10 micron emission is from heated dust grains. Instead, it is believed the 10 micron radiation is nonthermal in origin, implying a remarkably small size of only 0.1 AU for this source.

Safe-Taipei a Program Project for Strong Motions, Active Faults, and Earthquakes in the Taipei Metropolitan Area

NASA Astrophysics Data System (ADS)

Wang, Jeen-Hwa

Strong collision between the Eurasian and Philippine Sea Plates causes high seismicity in the Taiwan region, which is often attacked by large earthquakes. Several cities, including three mega-cities, i.e., Taipei, Taichung, and Kaoshung, have been constructed on western Taiwan, where is lying on thick sediments. These cities, with a high-population density, are usually a regional center of culture, economics, and politics. Historically, larger-sized earthquakes, e.g. the 1935 Hsingchu—Taichung earthquake and the 1999 Chi—Chi earthquake, often caused serious damage on the cities. Hence, urban seismology must be one of the main subjects of Taiwan's seismological community. Since 2005, a program project, sponsored by Academia Sinica, has been launched to investigate seismological problems in the Taipei Metropolitan Area. This program project is performed during the 2005—2007 period. The core research subjects are: (1) the deployment of the Taipei Down-hole Seismic Array; (2) the properties of earthquakes and active faults in the area; (3) the seismogenic-zone structures, including the 3-D velocity and Q structures, of the area; (4) the characteristics of strong-motions and sites affects; and (5) strong-motion prediction. In addition to academic goals, the results obtained from the program project will be useful for seismic hazard mitigation not only for the area but also for others.

High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

PubMed

Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

2015-11-02

A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

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

Milton, Flora Aparecida; Genomic Medicine, Houston Methodist Research Institute, Houston, TX; Cvoro, Aleksandra

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1more » adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation.« less

Strong quantum coherence between Fermi liquid Mahan excitons

DOE PAGES

Paul, J.; Stevens, C. E.; Liu, C.; ...

2016-04-14

In modulation doped quantum wells, the excitons are formed as a result of the interactions of the charged holes with the electrons at the Fermi edge in the conduction band, leading to the so-called “Mahan excitons.” The binding energy of Mahan excitons is expected to be greatly reduced and any quantum coherence destroyed as a result of the screening and electron-electron interactions. Surprisingly, we observe strong quantum coherence between the heavy hole and light hole excitons. Such correlations are revealed by the dominating cross-diagonal peaks in both one-quantum and two-quantum two-dimensional Fourier transform spectra. Theoretical simulations based on the opticalmore » Bloch equations where many-body effects are included phenomenologically reproduce well the experimental spectra. Furthermore, time-dependent density functional theory calculations provide insight into the underlying physics and attribute the observed strong quantum coherence to a significantly reduced screening length and collective excitations of the many-electron system.« less

Strong Quantum Coherence between Fermi Liquid Mahan Excitons

NASA Astrophysics Data System (ADS)

Paul, J.; Stevens, C. E.; Liu, C.; Dey, P.; McIntyre, C.; Turkowski, V.; Reno, J. L.; Hilton, D. J.; Karaiskaj, D.

2016-04-01

In modulation doped quantum wells, the excitons are formed as a result of the interactions of the charged holes with the electrons at the Fermi edge in the conduction band, leading to the so-called "Mahan excitons." The binding energy of Mahan excitons is expected to be greatly reduced and any quantum coherence destroyed as a result of the screening and electron-electron interactions. Surprisingly, we observe strong quantum coherence between the heavy hole and light hole excitons. Such correlations are revealed by the dominating cross-diagonal peaks in both one-quantum and two-quantum two-dimensional Fourier transform spectra. Theoretical simulations based on the optical Bloch equations where many-body effects are included phenomenologically reproduce well the experimental spectra. Time-dependent density functional theory calculations provide insight into the underlying physics and attribute the observed strong quantum coherence to a significantly reduced screening length and collective excitations of the many-electron system.

Strong Quantum Coherence between Fermi Liquid Mahan Excitons.

PubMed

Paul, J; Stevens, C E; Liu, C; Dey, P; McIntyre, C; Turkowski, V; Reno, J L; Hilton, D J; Karaiskaj, D

2016-04-15

In modulation doped quantum wells, the excitons are formed as a result of the interactions of the charged holes with the electrons at the Fermi edge in the conduction band, leading to the so-called "Mahan excitons." The binding energy of Mahan excitons is expected to be greatly reduced and any quantum coherence destroyed as a result of the screening and electron-electron interactions. Surprisingly, we observe strong quantum coherence between the heavy hole and light hole excitons. Such correlations are revealed by the dominating cross-diagonal peaks in both one-quantum and two-quantum two-dimensional Fourier transform spectra. Theoretical simulations based on the optical Bloch equations where many-body effects are included phenomenologically reproduce well the experimental spectra. Time-dependent density functional theory calculations provide insight into the underlying physics and attribute the observed strong quantum coherence to a significantly reduced screening length and collective excitations of the many-electron system.

Reduced administered activity, reduced acquisition time, and preserved image quality for the new CZT camera.

PubMed

Oddstig, Jenny; Hedeer, Fredrik; Jögi, Jonas; Carlsson, Marcus; Hindorf, Cecilia; Engblom, Henrik

2013-02-01

For a 1-day myocardial perfusion SPECT (MPS) the recommendations for administered activity stated in the EANM guidelines results in an effective dose of up to 16 mSv per patient. Recently, a gamma camera system, based on cadmium zinc telluride (CZT) technology, was introduced. This technique has the potential to reduce the effective dose and scan time compared to the conventional NaI gamma camera. The aim of this study was to investigate if the effective dose can be reduced with a preserved image quality using CZT technology in MPS. In total, 150 patients were included in the study. All underwent a 1-day (99m)Tc-tetrofosmin stress-rest protocol and were divided into three subgroups (n = 50 in each group) with 4, 3, and 2.5 MBq/kg body weight of administered activity in the stress examination, respectively. The acquisition time was increased in proportion to the decrease in administered activity. All examinations were analyzed for image quality by visual grading on a 4-point scale (1 = poor, 2 = adequate, 3 = good, 4 = excellent), by two expert readers. The total effective dose (stress + rest) decreased from 9.3 to 5.8 mSv comparing 4 to 2.5 MBq/kg body weight. For the patients undergoing stress examination only (35%) the effective dose, administrating 2.5 MBq/kg, was 1.4 mSv. The image acquisition times for 2.5 MBq/kg body weight were 475 and 300 seconds (stress and rest) compared to 900 seconds for each when using conventional MPS. The average image quality was 3.7 ± 0.5, 3.8 ± 0.5, and 3.8 ± 0.4 for the stress images and 3.5 ± 0.6, 3.6 ± 0.6, and 3.5 ± 0.6 for the rest images and showed no statistically significant difference (P = .62) among the 4, 3, and 2.5 MBq/kg groups. The new CZT technology can be used to considerably decrease the effective dose and acquisition time for MPS with preserved high image quality.

Emerging Signs of Strong Reciprocity in Human Ontogeny

PubMed Central

Robbins, Erin; Rochat, Philippe

2011-01-01

Strong reciprocity is considered here as the propensity to sacrifice resources to be kind or to punish in response to prior acts, a behavior not simply reducible to self-interest and a likely force behind human cooperation and sociality. The aim was to capture emerging signs of strong reciprocity in human ontogeny and across highly contrasted cultures. Three- and 5-year-old middle class American children (N = 162) were tested in a simple, multiple round, three-way sharing game involving the child, a generous puppet, and a stingy puppet. At the end of the game, the child was offered an opportunity to sacrifice some of her personal gains to punish one of the puppets. By 3 years, American children demonstrate a willingness to engage in costly punishment. However, only 5-year-olds show some evidence of strong reciprocity by orienting their punishment systematically toward the stingy puppet. Further analyses and three additional control conditions demonstrate that such propensity is not simply reducible to (a) straight imitation, or (b) inequity aversion. To assess the relative universality of such development, a group of 5- to 6-year-old children from rural Samoa (N = 14) were tested and compared to age and gender-matched American children. Samoan children did not manifest the same propensity toward strong reciprocity. The results are interpreted as pointing to (1) the developmental emergence of an ethical stance between 3 and 5 years of age, and (2) that the expression of such stance by young children could depend on culture. PMID:22194730

Reduced variability of auditory alpha activity in chronic tinnitus.

PubMed

Schlee, Winfried; Schecklmann, Martin; Lehner, Astrid; Kreuzer, Peter M; Vielsmeier, Veronika; Poeppl, Timm B; Langguth, Berthold

2014-01-01

Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8-10 Hz) but not for the upper alpha band (10-12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus.

Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors.

PubMed

Liu, Yang; Peng, Xia; Guan, Xiaocong; Lu, Dong; Xi, Yong; Jin, Shiyu; Chen, Hui; Zeng, Limin; Ai, Jing; Geng, Meiyu; Hu, Youhong

2017-01-27

FGF receptors (FGFRs) are tyrosine kinases that are overexpressed in diverse tumors by genetic alterations such as gene amplifications, somatic mutations and translocations. Owing to this characteristic, FGFRs are attractive targets for cancer treatment. It has been demonstrated that most multi-targeted, ATP competitive tyrosine kinase inhibitors are active against FGFRs as well as other kinases. The design of new and more selective inhibitors of FGFRs, which might be reduced off-target and side effects, is a difficult yet significant challenge. The results of the current investigation, show that novel Ponatinib analogues are highly active as FGFR inhibitors and that they possess reduced kinase insert domain receptor (KDR) activities. Observations made in a structure and activity relationship (SAR) investigation led to the development of a promising, orally available lead compound 4, which displays a 50-100 fold in vitro selectivity for inhibition of FGFR1-3 over KDR. In addition, biological evaluation of compound 4 showed that it displays significant antitumor activities in FGFR1-amplificated H1581 and FGFR2-amplificated SNU-16 xenograft models. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Electronic properties of bilayer graphenes strongly coupled to interlayer stacking and an external field

DOE PAGES

Park, Changwon; Ryou, Junga; Hong, Suklyun; ...

2015-07-02

Bilayer graphene (BLG) with a tunable band gap appears interesting as an alternative to graphene for practical applications; thus, its transport properties are being actively pursued. Using density functional theory and perturbation analysis, we investigated, under an external electric field, the electronic properties of BLG in various stackings relevant to recently observed complex structures. We established the first phase diagram summarizing the stacking-dependent gap openings of BLG for a given field. Lastly, we further identified high-density midgap states, localized on grain boundaries, even under a strong field, which can considerably reduce the overall transport gap.

Crossover from weak to strong localization in quasi-1D = conductors.

NASA Astrophysics Data System (ADS)

Gershenson, M. E.; Khavin, Y. B.; Mikhalchuk, A. G.; Bozler, H. M.; Bogdanov, A. L.

1997-03-01

A crossover from weak localization (WL) to strong localization (SL) with decreasing temperature has been observed in the resistance of quasi-1D channels in Si delta-doped GaAs structures. The crossover occurs when the phase-breaking length becomes comparable to the localization length. In the SL regime, an activation temperature dependence R(T) is observed. The activation energy is very close to the spacing between the energy levels of the localized electrons within the localization domain. The activation energy decreases by half in strong magnetic fields, as a result, an exponentially strong negative magnetoresistance is developed. All the features of the magnetoresistance in the SL regime are in good agreement with the theory of doubling of the localization length in quasi-1D conductors in strong fields. The magnetoresistance provides a direct measurement of the localization length. Supported by RNFBR, INTAS 943862, and NSF DRM-9623716 (A.G.M. and H.M.B.)

Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

USDA-ARS?s Scientific Manuscript database

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

Strong cellulase inhibition by Mannan polysaccharides in cellulose conversion to sugars.

PubMed

Kumar, Rajeev; Wyman, Charles E

2014-07-01

Cellulase enzymes contribute a major fraction of the total cost for biological conversion of lignocellulosic biomass to fuels and chemicals. Although a several fold reduction in cellulase production costs and enhancement of cellulase activity and stability have been reported in recent years, sugar yields are still lower at low enzyme doses than desired commercially. We recently reported that hemicellulose xylan and its oligomers strongly inhibit cellulase and that supplementation of cellulase with xylanase and β-xylosidase would significantly reduce such inhibition. In this study, mannan polysaccharides and their enzymatically prepared hydrolyzates were discovered to be strongly inhibitory to fungal cellulase in cellulose conversion (>50% drop in % relative conversion), even at a small concentration of 0.1 g/L, and inhibition was much greater than experienced by other known inhibitors such as cellobiose, xylooligomers, and furfural. Furthermore, cellulase inhibition dramatically increased with heteromannan loading and mannan substitution with galactose side units. In general, enzymatically prepared hydrolyzates were less inhibitory than their respective mannan polysaccharides except highly substituted ones. Supplementation of cellulase with commercial accessory enzymes such as xylanase, pectinase, and β-glucosidase was effective in greatly relieving inhibition but only for less substituted heteromannans. However, cellulase supplementation with purified heteromannan specific enzymes relieved inhibition by these more substituted heteromannans as well, suggesting that commercial preparations need to have higher amounts of such activities to realize high sugar yields at the low enzyme protein loadings needed for low cost fuels production. © 2014 Wiley Periodicals, Inc.

Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells

PubMed Central

Wang, Jueqiong; Lu, Liu; Kok, Chung H.; Saunders, Verity A.; Goyne, Jarrad M.; Dang, Phuong; Leclercq, Tamara M.; Hughes, Timothy P.; White, Deborah L.

2017-01-01

Imatinib is actively transported by organic cation transporter-1 (OCT-1) influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Herein we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor γ agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor γ antagonists (GW9662, T0070907) increase OCT-1 activity. Importantly, these effects can lead to corresponding changes in sensitivity to BCR-ABL kinase inhibition. Results were confirmed in peroxisome proliferator-activated receptor γ-transduced K562 cells. Furthermore, we identified a strong negative correlation between OCT-1 activity and peroxisome proliferator-activated receptor γ transcriptional activity in diagnostic chronic myeloid leukemia patients (n=84; P<0.0001), suggesting that peroxisome proliferator-activated receptor γ activation has a negative impact on the intracellular uptake of imatinib and consequent BCR-ABL kinase inhibition. The inter-patient variability of peroxisome proliferator-activated receptor γ activation likely accounts for the heterogeneity observed in patient OCT-1 activity at diagnosis. Recently, the peroxisome proliferator-activated receptor γ agonist pioglitazone was reported to act synergistically with imatinib, targeting the residual chronic myeloid leukemia stem cell pool. Our findings suggest that peroxisome proliferator-activated receptor γ ligands have differential effects on circulating mononuclear cells compared to stem cells. Since the effect of peroxisome proliferator-activated receptor γ activation on imatinib uptake in mononuclear cells may counteract the clinical benefit of this activation in stem cells, caution should be applied when combining these therapies, especially in

Synthesis of High Valence Silver-Loaded Mesoporous Silica with Strong Antibacterial Properties

PubMed Central

Chen, Chun-Chi; Wu, Hsin-Hsien; Huang, Hsin-Yi; Liu, Chen-Wei; Chen, Yi-Ning

2016-01-01

A simple chemical method was developed for preparing high valence silver (Ag)-loaded mesoporous silica (Ag-ethylenediaminetetraacetic acid (EDTA)-SBA-15), which showed strong antibacterial activity. Ag-EDTA-SBA-15 exhibited stronger and more effective antibacterial activity than commercial Ag nanoparticles did, and it offered high stability of high valence silver in the porous matrix and long-lasting antibacterial activity. The synthesized materials were characterized using Fourier transform infrared spectroscopy, powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) analysis, and transmission electron microscopy (TEM). Ag existed in both surface complexation and Ag particles. EDTA anchored within a porous structure chelated Ag ions in higher oxidation states and prevented their agglomeration and oxidation reduction. The XRD results showed that most Ag in the Ag-EDTA-SBA-15 existed in higher oxidation states such as Ag(II) and Ag(III). However, the XPS and TEM results showed that Ag easily reduced in lower oxidation states and agglomerated as Ag particles on the exterior layer of the SBA-15. PMID:26742050

Prevalence and work-related risk factors for reduced activities and absenteeism due to low back symptoms.

PubMed

Widanarko, Baiduri; Legg, Stephen; Stevenson, Mark; Devereux, Jason; Eng, Amanda; 't Mannetje, Andrea; Cheng, Soo; Pearce, Neil

2012-07-01

Although quite a lot is known about the risk factors for low back symptoms (LBS), less is known about the risk factors for the consequences of LBS. A sample of 3003 men and women randomly selected from the New Zealand Electoral Roll, were interviewed by telephone about self reported physical, psychosocial, organizational, environmental factors and the consequences of LBS (i.e. self-reported reduced activities and absenteeism). The 12-month period prevalence of reduced activities and absenteeism were 18% and 9%, respectively. Lifting (OR 1.79 95% CI 1.16-2.77) increased the risk of reduced activities. Working in awkward/tiring positions (OR 2.11 95% CI 1.20-3.70) and in a cold/damp environment (OR 2.18 95% CI 1.11-4.28) increased the risk of absenteeism. Among those with LBS, reduced activities increased with working in a hot/warm environment (OR 2.14 95% CI 1.22-3.76) and absenteeism was increased with work in awkward/tiring positions (OR 2.06 95% CI 1.13-3.77), tight deadlines (OR 1.89 95% CI 1.02-3.50), and a hot/warm environment (OR 3.35 95% CI 1.68-6.68). Interventions to reduce the consequences of LBS should aim to reduce awkward/tiring positions, lifting and work in a cold/damp environment. For individuals with LBS, additional focus should be to reduce tight deadlines, and work in hot/warm environments. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Reduced feeding activity of soil detritivores under warmer and drier conditions

NASA Astrophysics Data System (ADS)

Thakur, Madhav P.; Reich, Peter B.; Hobbie, Sarah E.; Stefanski, Artur; Rich, Roy; Rice, Karen E.; Eddy, William C.; Eisenhauer, Nico

2018-01-01

Anthropogenic warming is projected to trigger positive feedbacks to climate by enhancing carbon losses from the soil1. While such losses are, in part, due to increased decomposition of organic matter by invertebrate detritivores, it is unknown how detritivore feeding activity will change with warming2, especially under drought conditions. Here, using four-year manipulation experiments in two North American boreal forests, we investigate how temperature (ambient, ambient + 1.7 °C and ambient + 3.4 °C) and rainfall (ambient and -40% of the summer precipitation) perturbations influence detritivore feeding activity. In contrast to general expectations1,3, warming had negligible net effects on detritivore feeding activity at ambient precipitation. However, when combined with precipitation reductions, warming decreased feeding activity by 14%. Across all plots and dates, detritivore feeding activity was positively associated with bulk soil microbial respiration. These results suggest slower rates of decomposition of soil organic matter and thus reduced positive feedbacks to climate under anthropogenic climate change.

Kinetic energy budget during strong jet stream activity over the eastern United States

NASA Technical Reports Server (NTRS)

Fuelberg, H. E.; Scoggins, J. R.

1980-01-01

Kinetic energy budgets are computed during a cold air outbreak in association with strong jet stream activity over the eastern United States. The period is characterized by large generation of kinetic energy due to cross-contour flow. Horizontal export and dissipation of energy to subgrid scales of motion constitute the important energy sinks. Rawinsonde data at 3 and 6 h intervals during a 36 h period are used in the analysis and reveal that energy fluctuations on a time scale of less than 12 h are generally small even though the overall energy balance does change considerably during the period in conjunction with an upper level trough which moves through the region. An error analysis of the energy budget terms suggests that this major change in the budget is not due to random errors in the input data but is caused by the changing synoptic situation. The study illustrates the need to consider the time and space scales of associated weather phenomena in interpreting energy budgets obtained through use of higher frequency data.

Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption

PubMed Central

Sandhu, Eleanor C.; Fernando, Anushka B. P.; Tossell, Kyoko; Kokkinou, Michelle; Glegola, Justyna; Howes, Oliver D.

2018-01-01

Abstract Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice. Strikingly, optogenetic excitation of dopamine neurons decreased salt intake in a rapid and reversible manner, despite a strong salt appetite. Importantly, optogenetic excitation was not aversive, did not induce hyperactivity, and did not alter salt concentration preferences in a need-free state. In addition, we found that chemogenetic inhibition of dopamine neurons had no effect on salt intake. Lastly, optogenetic excitation of dopamine neurons reduced consumption of sucrose following an overnight fast, suggesting a more general role of VTA dopamine neuron excitation in organizing motivated behaviors. PMID:29766048

Controlled release and long-term antibacterial activity of reduced graphene oxide/quaternary ammonium salt nanocomposites prepared by non-covalent modification.

PubMed

Ye, Xiaoli; Feng, Jin; Zhang, Jingxian; Yang, Xiujiang; Liao, Xiaoyan; Shi, Qingshan; Tan, Shaozao

2017-01-01

In order to control the long-term antibacterial property of quaternary ammonium salts, dodecyl dimethyl benzyl ammonium chloride (rGO-1227) and rGO-bromohexadecyl pyridine (rGO-CPB) were self-assembled on surfaces of reduced graphene oxide (rGO) via π-π interactions. The obtained rGO-1227 and rGO-CPB nanocompounds were characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM).The antibacterial activities were evaluated on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Both rGO-CPB and rGO-1227 reduced the cytotoxicity of the pure antimicrobial agents and presented strong antimicrobial properties. Especially, CPB could be loaded efficiently on the surface of rGO via π-π conjugate effect, which resulted in a nanocomposite presenting a long-term antibacterial capability due to the more important quantity of free π electrons compared to that of 1227. When comparing the advantages of both prepared nanocomposites, rGO-CPB displayed a better specific-targeting capability and a longer-term antibacterial property. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards an integrated European strong motion data distribution

NASA Astrophysics Data System (ADS)

Luzi, Lucia; Clinton, John; Cauzzi, Carlo; Puglia, Rodolfo; Michelini, Alberto; Van Eck, Torild; Sleeman, Reinhoud; Akkar, Sinan

2013-04-01

Recent decades have seen a significant increase in the quality and quantity of strong motion data collected in Europe, as dense and often real-time and continuously monitored broadband strong motion networks have been constructed in many nations. There has been a concurrent increase in demand for access to strong motion data not only from researchers for engineering and seismological studies, but also from civil authorities and seismic networks for the rapid assessment of ground motion and shaking intensity following significant earthquakes (e.g. ShakeMaps). Aside from a few notable exceptions on the national scale, databases providing access to strong motion data has not appeared to keep pace with these developments. In the framework of the EC infrastructure project NERA (2010 - 2014), that integrates key research infrastructures in Europe for monitoring earthquakes and assessing their hazard and risk, the network activity NA3 deals with the networking of acceleration networks and SM data. Within the NA3 activity two infrastructures are being constructed: i) a Rapid Response Strong Motion (RRSM) database, that following a strong event, automatically parameterises all available on-scale waveform data within the European Integrated waveform Data Archives (EIDA) and makes the waveforms easily available to the seismological community within minutes of an event; and ii) a European Strong Motion (ESM) database of accelerometric records, with associated metadata relevant to earthquake engineering and seismology research communities, using standard, manual processing that reflects the state of the art and research needs in these fields. These two separate repositories form the core infrastructures being built to distribute strong motion data in Europe in order to guarantee rapid and long-term availability of high quality waveform data to both the international scientific community and the hazard mitigation communities. These infrastructures will provide the access to

Reverse actin sliding triggers strong myosin binding that moves tropomyosin

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

Bekyarova, T.I.; Reedy, M.C.; Baumann, B.A.J.

2008-09-03

Actin/myosin interactions in vertebrate striated muscles are believed to be regulated by the 'steric blocking' mechanism whereby the binding of calcium to the troponin complex allows tropomyosin (TM) to change position on actin, acting as a molecular switch that blocks or allows myosin heads to interact with actin. Movement of TM during activation is initiated by interaction of Ca{sup 2+} with troponin, then completed by further displacement by strong binding cross-bridges. We report x-ray evidence that TM in insect flight muscle (IFM) moves in a manner consistent with the steric blocking mechanism. We find that both isometric contraction, at highmore » [Ca{sup 2+}], and stretch activation, at lower [Ca{sup 2+}], develop similarly high x-ray intensities on the IFM fourth actin layer line because of TM movement, coinciding with x-ray signals of strong-binding cross-bridge attachment to helically favored 'actin target zones.' Vanadate (Vi), a phosphate analog that inhibits active cross-bridge cycling, abolishes all active force in IFM, allowing high [Ca{sup 2+}] to elicit initial TM movement without cross-bridge attachment or other changes from relaxed structure. However, when stretched in high [Ca{sup 2+}], Vi-'paralyzed' fibers produce force substantially above passive response at pCa {approx} 9, concurrent with full conversion from resting to active x-ray pattern, including x-ray signals of cross-bridge strong-binding and TM movement. This argues that myosin heads can be recruited as strong-binding 'brakes' by backward-sliding, calcium-activated thin filaments, and are as effective in moving TM as actively force-producing cross-bridges. Such recruitment of myosin as brakes may be the major mechanism resisting extension during lengthening contractions.« less

The STRONG STAR Multidisciplinary PTSD Research Consortium

DTIC Science & Technology

2009-09-01

superior A.5 Role of the Serotonin Transporter and Serotonergic Hypotheses related to Alcoholism Vulnerability Due to Low Serotonin. Strong...evidence shows that the biological vulnerability of EOA patients may be related to a serotonergic dysfunction (Johnson, 2000; Johnson and Ait-Daoud...transporter (Johnson et al., 2008). These findings of reduced serotonergic functioning in L-carriers is contrary to previous data indicating that the L

Magnolol reduces UVB-induced photodamage by regulating matrix metalloproteinase activity.

PubMed

Im, A-Rang; Song, Jae Hyoung; Lee, Mi Young; Chae, Sungwook

2015-01-01

In this study, we evaluated the anti-photoaging activity of magnolol in UV-irradiated hairless mice, and hypothesized that magnolol would prevent photoaging in these animals. The inhibitory effect of magnolol on wrinkle formation was determined by analyzing the skin replica, histologically examining the epidermal thickness, and identifying damage to the collagen fibers. The protective effects of magnolol on UVB-induced skin photoaging were examined by determining the level of MMPs and mitogen-activated protein kinases (MAPKs). Exposure to UVB radiation significantly increased skin thickness and wrinkle grade, but magnolol treatment significantly reduced the average length and depth of wrinkles, and this was correlated with the inhibition of collagen fiber loss. The magnolol-treated group had remarkably decreased activity levels of MMP-1, -9, and -13 compared to the corresponding levels in the vehicle-treated UVB-irradiated group. These results indicate that magnolol prevents skin photoaging in UVB-irradiated hairless mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

PubMed Central

Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

2015-01-01

AIM: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. METHODS: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. RESULTS: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD+ (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation.

PubMed

Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

2015-07-14

To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD(+), a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD(+) (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced

Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

PubMed

Briffa, Jessica F; Grinfeld, Esther; McAinch, Andrew J; Poronnik, Philip; Hryciw, Deanne H

2014-01-25

Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release.

PubMed

Park, Daehun; Lee, Unghwi; Cho, Eunji; Zhao, Haiyan; Kim, Jung Ah; Lee, Byoung Ju; Regan, Philip; Ho, Won-Kyung; Cho, Kwangwook; Chang, Sunghoe

2018-03-20

Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD) of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool. Moreover, it induced a strong frequency-dependent short-term depression of synaptic release, even under the condition of sufficient release-ready SVs. Super-resolution microscopy further proved the defects in SV protein clearance induced by KD. Thus, reduced expression of SCAMP5 may impair the efficiency of SV clearance at the active zone, and this might relate to the synaptic dysfunction observed in autism. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Critical behavior in trapped strongly interacting Fermi gases

NASA Astrophysics Data System (ADS)

Taylor, E.

2009-08-01

We investigate the width of the Ginzburg critical region and experimental signatures of critical behavior in strongly interacting trapped Fermi gases close to unitarity, where the s -wave scattering length diverges. Despite the fact that the width of the critical region is of the order unity, evidence of critical behavior in the bulk thermodynamics of trapped gases is strongly suppressed by their inhomogeneity. The specific heat of a harmonically confined gas, for instance, is linear in the reduced temperature t=(T-Tc)/Tc above Tc . We also discuss the prospects of observing critical behavior in the local compressibility from measurements of the density profile.

Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption

PubMed Central

Vengeliene, Valentina; Noori, Hamid R; Spanagel, Rainer

2015-01-01

Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. PMID:25994077

Deferasirox has strong anti-leukemia activity but may antagonize theanti-leukemia effect of doxorubicin.

PubMed

Chang, Yu-Chien; Lo, Wen-Jyi; Huang, Yu-Ting; Lin, Chaio-Lin; Feng, Chiu-Che; Lin, Hsin-Ting; Cheng, Hsu-Chen; Yeh, Su-Peng

2017-09-01

Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients. DFX induces cell cycle arrest at G1 phase and apoptosis and inhibits phosphorylation of ERK. We also showed that DFX antagonizes the anti-leukemic effect of DOX. On the contrary, combining DFX with Ara-C created a synergistic effect. Our study confirms the anti-leukemia activity of DFX and provides important information on how to select a partner drug for DFX for the treatment of AML in future clinical trials.

Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.

PubMed Central

Thorburn, A W; Gumbiner, B; Bulacan, F; Brechtel, G; Henry, R R

1991-01-01

To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM. PMID:1899428

Contrasting effects of strong ties on SIR and SIS processes in temporal networks

NASA Astrophysics Data System (ADS)

Sun, Kaiyuan; Baronchelli, Andrea; Perra, Nicola

2015-12-01

Most real networks are characterized by connectivity patterns that evolve in time following complex, non-Markovian, dynamics. Here we investigate the impact of this ubiquitous feature by studying the Susceptible-Infected-Recovered (SIR) and Susceptible-Infected-Susceptible (SIS) epidemic models on activity driven networks with and without memory (i.e., Markovian and non-Markovian). We find that memory inhibits the spreading process in SIR models by shifting the epidemic threshold to larger values and reducing the final fraction of recovered nodes. On the contrary, in SIS processes memory reduces the epidemic threshold and, for a wide range of disease parameters, increases the fraction of nodes affected by the disease in the endemic state. The heterogeneity in tie strengths, and the frequent repetition of strong ties it entails, allows in fact less virulent SIS-like diseases to survive in tightly connected local clusters that serve as reservoir for the virus. We validate this picture by studying both processes on two real temporal networks.

Mitogen-activated protein kinase inhibition reduces mucin 2 production and mucinous tumor growth.

PubMed

Dilly, Ashok K; Song, Xinxin; Zeh, Herbert J; Guo, Zong S; Lee, Yong J; Bartlett, David L; Choudry, Haroon A

2015-10-01

Excessive accumulation of mucin 2 (MUC2) protein (a gel-forming secreted mucin) within the peritoneal cavity is the major cause of morbidity and mortality in pseudomyxoma peritonei (PMP), a unique mucinous malignancy of the appendix. Mitogen-activated protein kinase (MAPK) signaling pathway is upregulated in PMP and has been shown to modulate MUC2 promoter activity. We hypothesized that targeted inhibition of the MAPK pathway would be a novel, effective, and safe therapeutic strategy to reduce MUC2 production and mucinous tumor growth. We tested RDEA119, a specific MEK1/2 (MAPK extracellular signal-regulated kinase [ERK] kinase) inhibitor, in MUC2-secreting LS174T cells, human PMP explant tissue, and in a unique intraperitoneal murine xenograft model of PMP. RDEA119 reduced ERK1/2 phosphorylation and inhibited MUC2 messenger RNA and protein expression in vitro. In the xenograft model, chronic oral therapy with RDEA119 inhibited mucinous tumor growth in an MAPK pathway-dependent manner and this translated into a significant improvement in survival. RDEA119 downregulated phosphorylated ERK1/2 and nuclear factor κB p65 protein signaling and reduced activating protein 1 (AP1) transcription factor binding to the MUC2 promoter in LS174T cells. This study provides a preclinical rationale for the use of MEK inhibitors to treat patients with PMP. Copyright © 2015 Elsevier Inc. All rights reserved.

orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET.

PubMed

DeGennaro, Matthew; McBride, Carolyn S; Seeholzer, Laura; Nakagawa, Takao; Dennis, Emily J; Goldman, Chloe; Jasinskiene, Nijole; James, Anthony A; Vosshall, Leslie B

2013-06-27

Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.

Strong coupling of collection of emitters on hyperbolic meta-material

NASA Astrophysics Data System (ADS)

Biehs, Svend-Age; Xu, Chenran; Agarwal, Girish S.

2018-04-01

Recently, considerable effort has been devoted to the realization of a strong coupling regime of the radiation matter interaction in the context of an emitter at a meta surface. The strong interaction is well realized in cavity quantum electrodynamics, which also show that strong coupling is much easier to realize using a collection of emitters. Keeping this in mind, we study if emitters on a hyperbolic meta materials can yield a strong coupling regime. We show that strong coupling can be realized for densities of emitters exceeding a critical value. A way to detect strong coupling between emitters and hyperbolic metamaterials is to use the Kretschman-Raether configuration. The strong coupling appears as the splitting of the reflectivity dip. In the weak coupling regime, the dip position shifts. The shift and splitting can be used to sense active molecules at surfaces.

Using Stable Isotopes to Assess Reduced Physical Activity of Individuals with Prader-Willi Syndrome.

ERIC Educational Resources Information Center

Davies, Peter S. W.; Joughlin, C.

1993-01-01

This study found that the physical activity levels of 10 children with Prader-Willi syndrome were significantly reduced in comparison to children without the syndrome. Increasing activity levels in children with Prader-Willi syndrome is suggested as a way to raise total energy expenditure and control weight gain. (Author/JDD)

Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain

PubMed Central

Caires, Rebeca; Luis, Enoch; Taberner, Francisco J.; Fernandez-Ballester, Gregorio; Ferrer-Montiel, Antonio; Balazs, Endre A.; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

2015-01-01

Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain. PMID:26311398

The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

PubMed

Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

2016-04-01

Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Tauroursodeoxycholic acid reduces glial cell activation in an animal model of acute neuroinflammation

PubMed Central

2014-01-01

Background Bile acids are steroid acids found predominantly in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is a neuroprotective agent in different animal models of stroke and neurological diseases. However, the anti-inflammatory properties of TUDCA in the central nervous system (CNS) remain unknown. Methods The acute neuroinflammation model of intracerebroventricular (icv) injection with bacterial lipopolysaccharide (LPS) in C57BL/6 adult mice was used herein. Immunoreactivity against Iba-1, GFAP, and VCAM-1 was measured in coronal sections in the mice hippocampus. Primary cultures of microglial cells and astrocytes were obtained from neonatal Wistar rats. Glial cells were treated with proinflammatory stimuli to determine the effect of TUDCA on nitrite production and activation of inducible enzyme nitric oxide synthase (iNOS) and NFκB luciferase reporters. We studied the effect of TUDCA on transcriptional induction of iNOS and monocyte chemotactic protein-1 (MCP-1) mRNA as well as induction of protein expression and phosphorylation of different proteins from the NFκB pathway. Results TUDCA specifically reduces microglial reactivity in the hippocampus of mice treated by icv injection of LPS. TUDCA treatment reduced the production of nitrites by microglial cells and astrocytes induced by proinflammatory stimuli that led to transcriptional and translational diminution of the iNOS. This effect might be due to inhibition of the NFκB pathway, activated by proinflammatory stimuli. TUDCA decreased in vitro microglial migration induced by both IFN-γ and astrocytes treated with LPS plus IFN-γ. TUDCA inhibition of MCP-1 expression induced by proinflammatory stimuli could be in part responsible for this effect. VCAM-1 inmunoreactivity in the hippocampus of animals treated by icv LPS was reduced by TUDCA treatment, compared to animals treated with LPS alone. Conclusions We show a triple anti-inflammatory effect of TUDCA on glial cells: i

Tauroursodeoxycholic acid reduces glial cell activation in an animal model of acute neuroinflammation.

PubMed

Yanguas-Casás, Natalia; Barreda-Manso, M Asunción; Nieto-Sampedro, Manuel; Romero-Ramírez, Lorenzo

2014-03-19

Bile acids are steroid acids found predominantly in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is a neuroprotective agent in different animal models of stroke and neurological diseases. However, the anti-inflammatory properties of TUDCA in the central nervous system (CNS) remain unknown. The acute neuroinflammation model of intracerebroventricular (icv) injection with bacterial lipopolysaccharide (LPS) in C57BL/6 adult mice was used herein. Immunoreactivity against Iba-1, GFAP, and VCAM-1 was measured in coronal sections in the mice hippocampus. Primary cultures of microglial cells and astrocytes were obtained from neonatal Wistar rats. Glial cells were treated with proinflammatory stimuli to determine the effect of TUDCA on nitrite production and activation of inducible enzyme nitric oxide synthase (iNOS) and NFκB luciferase reporters. We studied the effect of TUDCA on transcriptional induction of iNOS and monocyte chemotactic protein-1 (MCP-1) mRNA as well as induction of protein expression and phosphorylation of different proteins from the NFκB pathway. TUDCA specifically reduces microglial reactivity in the hippocampus of mice treated by icv injection of LPS. TUDCA treatment reduced the production of nitrites by microglial cells and astrocytes induced by proinflammatory stimuli that led to transcriptional and translational diminution of the iNOS. This effect might be due to inhibition of the NFκB pathway, activated by proinflammatory stimuli. TUDCA decreased in vitro microglial migration induced by both IFN-γ and astrocytes treated with LPS plus IFN-γ. TUDCA inhibition of MCP-1 expression induced by proinflammatory stimuli could be in part responsible for this effect. VCAM-1 inmunoreactivity in the hippocampus of animals treated by icv LPS was reduced by TUDCA treatment, compared to animals treated with LPS alone. We show a triple anti-inflammatory effect of TUDCA on glial cells: i) reduced glial cell activation, ii

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of natural antioxidants on colour stability, lipid oxidation and metmyoglobin reducing activity in raw beef patties.

PubMed

Liu, Fang; Xu, Qian; Dai, Ruitong; Ni, Yuanying

2015-01-01

Minced meats undergo oxidative changes and develop rancidity more quickly than intact muscle since grinding exposes more of the muscle surface to air and microbial contamination. Due to concerns about toxicological safety of synthetic antioxidants, recent studies have put more focus on natural antioxidant compounds derived from food components. The effects of four natural antioxidants (vitamin E, carnosine, grape seed extract and tea catechins) on oxidative processes and metmyoglobin reducing activity in raw beef patties during refrigerated (4°C) storage were investigated and the results were compared with butylated hydroxyanisole treatment patties. The correlation of lipid oxidation, colour and metmyoglobin reducing activity of beef patties were also studied. Samples treated with carnosine had the highest redness values on the eighth day. Tea catechins, vitamin E and grape seed extract showed higher protective effect against lipid oxidation than carnosine. Metmyoglobin reducing activity increased greatly in all samples during the storage. Significant correlation between redness value and lipid oxidation was demonstrated, while a weak correlation between metmyoglobin reducing activity and any other parameters was shown.

Trying To Reduce Your Technostress?: Helpful Activities for Teachers and Library Media Specialists.

ERIC Educational Resources Information Center

McKenzie, Barbara K.; And Others

1997-01-01

As pressure increases to integrate technology into instruction, many teachers and library media specialists are having difficulty coping with "technostress." Presents suggestions and activities for teachers and library media specialists designed to reduce "technostress." (PEN)

Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine autoimmune diabetes.

PubMed

Zou, Fang; Lai, Xiaoyang; Li, Jing; Lei, Shuihong; Hu, Lei

2017-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM. To this end, mouse studies were conducted to demonstrate that CatG impacts the activation of CD4+ T cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was investigated in NOD mice on the activation of CD4+ T cells, islet β cell function, islet inflammation and β-cell apoptosis. Furthermore, NOD mice were injected with CatG siRNA in early stage to observe the effect of CatG knockdown on the activation status of CD4+ T cells and the progression of diabetes. During the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually increased and the CD4+ T cells were gradually activated, resulting in more TH1 cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced the blood glucose level, improved the function of islet β cells and reduced the activation of CD4+ T cells. Early application of CatG siRNA improved the function of islet β cells, reduced islet inflammation and β cell apoptosis, and lowered the activation level of CD4+ T cells, thus slowing down the progression of diabetes.

Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine autoimmune diabetes

PubMed Central

Zou, Fang; Lai, Xiaoyang; Li, Jing; Lei, Shuihong; Hu, Lei

2017-01-01

Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM. To this end, mouse studies were conducted to demonstrate that CatG impacts the activation of CD4+ T cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was investigated in NOD mice on the activation of CD4+ T cells, islet β cell function, islet inflammation and β-cell apoptosis. Furthermore, NOD mice were injected with CatG siRNA in early stage to observe the effect of CatG knockdown on the activation status of CD4+ T cells and the progression of diabetes. During the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually increased and the CD4+ T cells were gradually activated, resulting in more TH1 cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced the blood glucose level, improved the function of islet β cells and reduced the activation of CD4+ T cells. Early application of CatG siRNA improved the function of islet β cells, reduced islet inflammation and β cell apoptosis, and lowered the activation level of CD4+ T cells, thus slowing down the progression of diabetes. PMID:29218110

Scintillation index of higher order mode laser beams in strong turbulence

NASA Astrophysics Data System (ADS)

Baykal, Yahya

2017-03-01

The scintillation index of higher order laser modes is examined in strong atmospheric turbulence. In our formulation, modified Rytov theory is employed with the inclusion of existing modified turbulence spectrum which presents the atmospheric turbulence spectrum as a linear filter having refractive and diffractive spatial frequency cutoffs. Variations of the scintillation index in strong atmospheric turbulence are shown against the weak turbulence plane wave scintillation index for various higher order laser modes of different sizes. Use of higher order modes in optical wireless communication links operating in strongly turbulent atmosphere is found to be advantageous in reducing the scintillation noise.

Radical-Scavenging Activity and Ferric Reducing Ability of Juniperus thurifera (L.), J. oxycedrus (L.), J. phoenicea (L.) and Tetraclinis articulata (L.)

PubMed Central

Kamal, Rabie; Marmouzi, Ilias; Zerrouki, Asmae; Cherrah, Yahia; Alaoui, Katim

2016-01-01

Objective. The aim of this work is to study and compare the antioxidant properties and phenolic contents of aqueous leaf extracts of Juniperus thurifera, Juniperus oxycedrus, Juniperus Phoenicea, and Tetraclinis articulata from Morocco. Methods. Antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging ability, Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP) assays. Also the total phenolic and flavonoids contents of the extracts were determined spectrophotometrically. Results. All the extracts showed interesting antioxidant activities compared to the standard antioxidants (butylated hydroxytoluene (BHT), quercetin, and Trolox). The aqueous extract of Juniperus oxycedrus showed the highest antioxidant activity as measured by DPPH, TEAC, and FRAP assays with IC50 values of 17.91 ± 0.37 μg/mL, 19.80 ± 0.55 μg/mL, and 24.23 ± 0.07 μg/mL, respectively. The strong correlation observed between antioxidant capacities and their total phenolic contents indicated that phenolic compounds were a major contributor to antioxidant properties of these plants extracts. Conclusion. These results suggest that the aqueous extracts of Juniperus thurifera, Juniperus oxycedrus, Juniperus phoenicea, and Tetraclinis articulata can constitute a promising new source of natural compounds with antioxidants ability. PMID:27293428

Polymerase III transcription factor B activity is reduced in extracts of growth-restricted cells.

PubMed Central

Tower, J; Sollner-Webb, B

1988-01-01

Extracts of cells that are down-regulated for transcription by RNA polymerase I and RNA polymerase III exhibit a reduced in vitro transcriptional capacity. We have recently demonstrated that the down-regulation of polymerase I transcription in extracts of cycloheximide-treated and stationary-phase cells results from a lack of an activated subform of RNA polymerase I which is essential for rDNA transcription. To examine whether polymerase III transcriptional down-regulation occurs by a similar mechanism, the polymerase III transcription factors were isolated and added singly and in pairs to control cell extracts and to extracts of cells that had reduced polymerase III transcriptional activity due to cycloheximide treatment or growth into stationary phase. These down-regulations result from a specific reduction in TFIIIB; TFIIIC and polymerase III activities remain relatively constant. Thus, although transcription by both polymerase III and polymerase I is substantially decreased in extracts of growth-arrested cells, this regulation is brought about by reduction of different kinds of activities: a component of the polymerase III stable transcription complex in the former case and the activated subform of RNA polymerase I in the latter. Images PMID:3352599

A Lactotransferrin Single Nucleotide Polymorphism Demonstrates Biological Activity That Can Reduce Susceptibility to Caries

PubMed Central

Toruner, Gokce A.; Velliyagounder, Kabilan; Sampathkumar, Vandana; Godboley, Dipti; Furgang, David

2013-01-01

Streptococcus mutans is prominently linked to dental caries. Saliva's influence on caries is incompletely understood. Our goal was to identify a salivary protein with anti-S. mutans activity, characterize its genotype, and determine genotypic variants associated with S. mutans activity and reduced caries. An S. mutans affinity column was used to isolate active moieties from saliva obtained from a subject with minimal caries. The bound and eluted protein was identified as lactotransferrin (LTF) by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis and confirmed by Western blotting with LTF antibody. A single nucleotide polymorphism (SNP) that produced a shift from arginine (R) to lysine (K) at amino acid position 47 in the LTF antimicrobial region (rs: 1126478) killed S. mutans in vitro. Saliva from a subject with moderate caries and with the LTF “wild-type” R form at position 47 had no such activity. A pilot genetic study (n = 30) showed that KK subjects were more likely to have anti-S. mutans activity than RR subjects (P = 0.001; relative risk = 3.6; 95% confidence interval [95% CI] = 1.5 to 11.13). Pretreatment of KK saliva with antibody to LTF reduced S. mutans killing in a dose-dependent manner (P = 0.02). KK subjects were less likely to have caries (P = 0.02). A synthetic 11-mer LTF/K peptide killed S. mutans and other caries-related bacteria, while the LTF/R peptide had no effect (P = 0.01). Our results provide functional evidence that the LTF/K variant results in both anti-S. mutans activity and reduced decay. We suggest that the LTF/K variant can influence oral microbial ecology in general and caries-provoking microbes specifically. PMID:23460521

Strong shock implosion, approximate solution

NASA Astrophysics Data System (ADS)

Fujimoto, Y.; Mishkin, E. A.; Alejaldre, C.

1983-01-01

The self-similar, center-bound motion of a strong spherical, or cylindrical, shock wave moving through an ideal gas with a constant, γ= cp/ cv, is considered and a linearized, approximate solution is derived. An X, Y phase plane of the self-similar solution is defined and the representative curved of the system behind the shock front is replaced by a straight line connecting the mappings of the shock front with that of its tail. The reduced pressure P(ξ), density R(ξ) and velocity U1(ξ) are found in closed, quite accurate, form. Comparison with numerically obtained results, for γ= {5}/{3} and γ= {7}/{5}, is shown.

Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

PubMed

Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

2016-03-01

Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research.

Endogenous flow-induced nitric oxide reduces superoxide-stimulated Na/H exchange activity via PKG in thick ascending limbs

PubMed Central

Garvin, Jeffrey L.

2014-01-01

Luminal flow stimulates endogenous nitric oxide (NO) and superoxide (O2−) production by renal thick ascending limbs (TALs). The delicate balance between these two factors regulates Na transport in TALs; NO enhances natriuresis, whereas O2− augments Na absorption. Endogenous, flow-stimulated O2− enhances Na/H exchange (NHE). Flow-stimulated NO reduces flow-induced O2−, a process mediated by cGMP-dependent protein kinase (PKG). However, whether flow-stimulated, endogenously-produced NO diminishes O2−-stimulated NHE activity and the signaling pathway involved are unknown. We hypothesized that flow-induced NO reduces the stimulation of NHE activity caused by flow-induced O2− via PKG in TALs. Intracellular pH recovery after an acid load was measured as an indicator of NHE activity in isolated, perfused rat TALs. l-Arginine, the NO synthase substrate, decreased NHE activity by 34 ± 5% (n = 5; P < 0.04). The O2− scavenger tempol decreased NHE activity by 46 ± 8% (n = 6; P < 0.004) in the absence of NO. In the presence of l-arginine, the inhibitory effect of tempol on NHE activity was reduced to −19 ± 6% (n = 6; P < 0.03). The soluble guanylate cyclase inhibitor LY-83583 blocked the effect of l-arginine thus restoring tempol's effect on NHE activity to −42 ± 4% (n = 6; P < 0.0005). The PKG inhibitor KT-5823 also inhibited l-arginine's effect on tempol-reduced NHE activity (−43 ± 5%; n = 5; P < 0.03). We conclude that flow-induced NO reduces the stimulatory effect of endogenous, flow-induced O2− on NHE activity in TALs via an increase in cGMP and PKG activation. PMID:25503735

Structural and mechanical properties of welded joints of reduced activation martensitic steels

NASA Astrophysics Data System (ADS)

Filacchioni, G.; Montanari, R.; Tata, M. E.; Pilloni, L.

2002-12-01

Gas tungsten arc welding and electron beam welding methods were used to realise welding pools on plates of reduced activation martensitic steels. Structural and mechanical features of these simulated joints have been investigated in as-welded and post-welding heat-treated conditions. The research allowed to assess how each welding technique affects the original mechanical properties of materials and to find suitable post-welding heat treatments. This paper reports results from experimental activities on BATMAN II and F82H mod. steels carried out in the frame of the European Blanket Project - Structural Materials Program.

Thermal properties of graphite oxide, thermally reduced graphene and chemically reduced graphene

NASA Astrophysics Data System (ADS)

Jankovský, Ondřej; Sedmidubský, David; Lojka, Michal; Sofer, Zdeněk

2017-07-01

We compared thermal behavior and other properties of graphite oxide, thermally reduced graphene and chemically reduced graphene. Graphite was oxidized according to the Hofmann method using potassium chlorate as oxidizing agent in strongly acidic environment. In the next step, the formed graphite oxide was chemically or thermally reduced yielding graphene. The mechanism of thermal reduction was studied using STA-MS. Graphite oxide and both thermally and chemically reduced graphenes were analysed by SEM, EDS, elemental combustion analysis, XPS, Raman spectroscopy, XRD and BET. These findings will help for the large scale production of graphene with appropriate chemical composition.

The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity

PubMed Central

Gu, Shoujin; Li, Wenjuan; Zhang, Hongtai; Fleming, Joy; Yang, Weiqiang; Wang, Shihua; Wei, Wenjing; Zhou, Jie; Zhu, Guofeng; Deng, Jiaoyu; Hou, Jian; Zhou, Ying; Lin, Shiqiang; Zhang, Xian-En; Bi, Lijun

2016-01-01

DNA polymerase III (DNA pol III) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in Mycobacterium tuberculosis (Mtb) requires further investigation. We have reconstituted the leading-strand replication process of the Mtb DNA pol III holoenzyme in vitro, and investigated the physical and functional relationships between its key components. We verify the presence of an αβ2ε polymerase-clamp-exonuclease replicase complex by biochemical methods and protein-protein interaction assays in vitro and in vivo and confirm that, in addition to the polymerase activity of its α subunit, Mtb DNA pol III has two potential proofreading subunits; the α and ε subunits. During DNA replication, the presence of the β2 clamp strongly promotes the polymerization of the αβ2ε replicase and reduces its exonuclease activity. Our work provides a foundation for further research on the mechanism by which the replication machinery switches between replication and proofreading and provides an experimental platform for the selection of antimicrobials targeting DNA replication in Mtb. PMID:26822057

Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method.

PubMed

Ozyürek, Mustafa; Bektaşoğlu, Burcu; Güçlü, Kubilay; Apak, Reşat

2009-03-16

Various dietary polyphenolics have been found to show an inhibitory effect on xanthine oxidase (XO) which mediates oxidative stress-originated diseases because of its ability to generate reactive oxygen species (ROS), including superoxide anion radical (O(2)(-)) and hydrogen peroxide. XO activity has usually been determined by following the rate of uric acid formation from xanthine-xanthine oxidase (X-XO) system using the classical XO activity assay (UV-method) at 295nm. Since some polyphenolics have strong absorption from the UV to visible region, XO-inhibitory activity of polyphenolics was alternatively determined without interference by directly measuring the formation of uric acid and hydrogen peroxide using the modified CUPRAC (cupric reducing antioxidant capacity) spectrophotometric method at 450nm. The CUPRAC absorbance of the incubation solution due to the reduction of Cu(II)-neocuproine reagent by the products of the X-XO system decreased in the presence of polyphenolics, the difference being proportional to the XO inhibition ability of the tested compound. The structure-activity relationship revealed that the flavones and flavonols with a 7-hydroxyl group such as apigenin, luteolin, kaempferol, quercetin, and myricetin inhibited XO-inhibitory activity at low concentrations (IC(50) values from 1.46 to 1.90microM), while the flavan-3-ols and naringin were less inhibitory. The findings of the developed method for quercetin and catechin in the presence of catalase were statistically alike with those of HPLC. In addition to polyphenolics, five kinds of herbs were evaluated for their XO-inhibitory activity using the developed method. The proposed spectrophotometric method was practical, low-cost, rapid, and could reliably assay uric acid and hydrogen peroxide in the presence of polyphenols (flavonoids, simple phenolic acids and hydroxycinnamic acids), and less open to interferences by UV-absorbing substances.

Cardiovascular function following reduced aerobic activity

NASA Technical Reports Server (NTRS)

Raven, P. B.; Welch-O'Connor, R. M.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

PubMed

LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

National Dissemination of StrongWomen–Healthy Hearts: A Community-Based Program to Reduce Risk of Cardiovascular Disease Among Midlife and Older Women

PubMed Central

Seguin, Rebecca A.; Chui, Kenneth K. H.; Clark, Valerie; Corbin, Marilyn A.; Goldberg, Jeanne P.; Heidkamp-Young, Eleanor; Lichtenstein, Alice H.; Wiker, Nancy; Nelson, Miriam E.

2015-01-01

Objectives. We describe the national dissemination of an evidence-based community cardiovascular disease prevention program for midlife and older women using the RE-AIM (reach effectiveness adoption implementation maintenance) framework and share key lessons learned during translation. Methods. In a 2010 to 2014 collaboration between the StrongWomen program and the National Extension Association of Family and Consumer Sciences, we assessed reach, adoption, implementation, and maintenance using survey methods, and we assessed effectiveness using a pretest–posttest within-participants design, with weight change as the primary outcome. Results. Overall reach into the population was 15 per 10 000. Of 85 trained leaders, 41 (48%) adopted the program. During the 12-week intervention, weight decreased by 0.5 kilograms, fruit and vegetable intake increased by 2.1 servings per day, and physical activity increased by 1238 metabolic equivalent (MET)-minutes per week (all P < .001). Average fidelity score was 4.7 (out of possible 5). Eleven of 41 adopting leaders (27%) maintained the program. Conclusions. The StrongWomen–Healthy Hearts program can be implemented with high fidelity in a variety of settings while remaining effective. These data provide direction for program modification to improve impact as dissemination continues. PMID:26469644

Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness.

PubMed

Watling, Christopher N; Smith, Simon S; Horswill, Mark S

2014-11-01

The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15-min nap break or a 15-min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break. Copyright © 2014 Society for Psychophysiological Research.

Strong nonadditivity as a key structure-activity relationship feature: distinguishing structural changes from assay artifacts.

PubMed

Kramer, Christian; Fuchs, Julian E; Liedl, Klaus R

2015-03-23

Nonadditivity in protein-ligand affinity data represents highly instructive structure-activity relationship (SAR) features that indicate structural changes and have the potential to guide rational drug design. At the same time, nonadditivity is a challenge for both basic SAR analysis as well as many ligand-based data analysis techniques such as Free-Wilson Analysis and Matched Molecular Pair analysis, since linear substituent contribution models inherently assume additivity and thus do not work in such cases. While structural causes for nonadditivity have been analyzed anecdotally, no systematic approaches to interpret and use nonadditivity prospectively have been developed yet. In this contribution, we lay the statistical framework for systematic analysis of nonadditivity in a SAR series. First, we develop a general metric to quantify nonadditivity. Then, we demonstrate the non-negligible impact of experimental uncertainty that creates apparent nonadditivity, and we introduce techniques to handle experimental uncertainty. Finally, we analyze public SAR data sets for strong nonadditivity and use recourse to the original publications and available X-ray structures to find structural explanations for the nonadditivity observed. We find that all cases of strong nonadditivity (ΔΔpKi and ΔΔpIC50 > 2.0 log units) with sufficient structural information to generate reasonable hypothesis involve changes in binding mode. With the appropriate statistical basis, nonadditivity analysis offers a variety of new attempts for various areas in computer-aided drug design, including the validation of scoring functions and free energy perturbation approaches, binding pocket classification, and novel features in SAR analysis tools.

Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.

PubMed

Amin, Ruhul; Asplin, John; Jung, Daniel; Bashir, Mohamed; Alshaikh, Altayeb; Ratakonda, Sireesha; Sharma, Sapna; Jeon, Sohee; Granja, Ignacio; Matern, Dietrich; Hassan, Hatim

2018-05-01

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets. Copyright © 2017 International Society of Nephrology. Published by

Toward Optimizing Vestibular Evoked Myogenic Potentials: Normalization Reduces the Need for Strong Neck Muscle Contraction.

PubMed

Noij, Kimberley S; Herrmann, Barbara S; Rauch, Steven D; Guinan, John J

2017-01-01

The cervical vestibular evoked myogenic potential (cVEMP) represents an inhibitory reflex of the saccule measured in the ipsilateral sternocleidomastoid muscle (SCM) in response to acoustic or vibrational stimulation. Since the cVEMP is a modulation of SCM electromyographic (EMG) activity, cVEMP amplitude is proportional to muscle EMG amplitude. We sought to evaluate muscle contraction influences on cVEMP peak-to-peak amplitudes (VEMPpp), normalized cVEMP amplitudes (VEMPn), and inhibition depth (VEMPid). cVEMPs at 500 Hz were measured in 25 healthy subjects for 3 SCM EMG contraction ranges: 45-65, 65-105, and 105-500 μV root mean square (r.m.s.). For each range, we measured cVEMP sound level functions (93-123 dB peSPL) and sound off, meaning that muscle contraction was measured without acoustic stimulation. The effect of muscle contraction amplitude on VEMPpp, VEMPn, and VEMPid and the ability to distinguish cVEMP presence/absence were evaluated. VEMPpp amplitudes were significantly greater at higher muscle contractions. In contrast, VEMPn and VEMPid showed no significant effect of muscle contraction. Cohen's d indicated that for all 3 cVEMP metrics contraction amplitude variations produced little change in the ability to distinguish cVEMP presence/absence. VEMPid more clearly indicated saccular output because when no acoustic stimulus was presented the saccular inhibition estimated by VEMPid was zero, unlike those by VEMPpp and VEMPn. Muscle contraction amplitude strongly affects VEMPpp amplitude, but contractions 45-300 μV r.m.s. produce stable VEMPn and VEMPid values. Clinically, there may be no need for subjects to exert high contraction effort. This is especially beneficial in patients for whom maintaining high SCM contraction amplitudes is challenging. © 2018 S. Karger AG, Basel.

Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling

PubMed Central

Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun; Wang, Xiaoke; Kherada, Nisharahmed; Desikan, Rajagopal; Mihai, Georgeta; Burns, Patrick; Sun, Qinghua; Rajagopalan, Sanjay

2016-01-01

Objective Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. Methods and Results Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. Conclusion Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID:26859892

Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia.

PubMed

Schoergenhofer, Christian; Schwameis, Michael; Gelbenegger, Georg; Buchtele, Nina; Thaler, Barbara; Mussbacher, Marion; Schabbauer, Gernot; Wojta, Johann; Jilma-Stohlawetz, Petra; Jilma, Bernd

2018-06-04

The protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11-49%), thrombin-anti-thrombin concentrations by 22% (-3 to 46%) and plasmin-anti-plasmin levels by 38% (23-53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (-11-71%), 50% (15-79%) and 23% (16-38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26-51%) and soluble E-selectin concentrations by 30% (25-38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia. Schattauer GmbH Stuttgart.

[Physical activity programmes to reduce overweight and obesity in children and adolescents; a systematic review].

PubMed

Aguilar Cordero, M J; Ortegón Piñero, A; Mur Vilar, N; Sánchez García, J C; García Verazaluce, J J; García García, I; Sánchez López, A M

2014-10-01

Obesity treatment has been the subject of much controversy; various authors have recommended the application of a comprehensive treatment programme, and in the light of this previous research, we consider the question of what is the most effective programme of physical activity to reduce overweight and obesity in children and adolescents. To analyse major studies on the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. Systematic review of the results of physical activity programmes, published in scientific articles, to reduce overweight and obesity. Using an automated database search in PubMed and Google Scholar, conducted from October 2013 to March 2014, we identified 85 valid items. In selecting the items, the criteria applied included the usefulness and relevance of the subject matter and the credibility or experience of the research study authors. The internal and external validity of each of the articles reviewed was taken into account. This review confirmed the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. The most effective programmes were those combining aerobic and anaerobic exercises. It is generally accepted that at least 180 minutes per week should be dedicated to exercise, in the form of three 60-minute sessions of moderate intensity. Such programmes could be sufficient for persons with overweight or obesity. Researchers in this field agree that when a diet based on an appropriate distribution of meals is combined with regular physical activity, they reinforce each other, and thus optimum results are obtained. Weight reduction programmes that take account of family involvement are more effective than nutrition education itself or other routine interventions that fail to consider family involvement. The role of pa rents and of the persons around the child or adolescent is essential to reinforce positive behaviour toward lifestyle change. Copyright AULA

Evaluation of Structure, Chaperone-Like Activity and Allergenicity of Reduced Glycated Adduct of Bovine β-casein.

PubMed

Yousefi, Reza; Ferdowsi, Leila; Tavaf, Zohreh; Sadeghian, Tanaz; Tamaddon, Ali M; Moghtaderi, Mozhgan; Pourpak, Zahra

2017-01-01

Milk has a potent reducing environment with an important quantity of sugar levels. In the current study β-casein was glycated in the presence of D-glucose and sodium cyanoborohydride as a reducing agent. Then, the reduced glucitol adduct of β-casein was used for the structural and functional analyses using different spectroscopic techniques. The results of fluorescence and far ultraviolet circular dichroism assessments suggest important structural alteration upon non-enzymatic glycation of β-casein. In addition, the chaperone activity, micellization properties and antioxidant activity of this protein were altered upon glucose modification. Also, as a result of reduced glycation, the allergenicity profile of this protein remained largely unchanged. Additional to its energetic and nutritional values, β-casein has important functional properties. The native structure of this protein is important to perform accurately its biological functions. Non-enzymatic glycation under reducing state was capable to alter both structural and functional aspects of β-casein. Due to effective reducing environment and significant quantity of reducing sugar of human milk, similar structural and functional alterations are most likely to occur upon reducing glycation of β-casein in vivo. Also, these changes might be even intensified during chronic hyperglycemia in diabetic mothers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI

PubMed Central

Frank, Sabine; Veit, Ralf; Sauer, Helene; Enck, Paul; Friederich, Hans-Christoph; Unholzer, Theresa; Bauer, Ute-Maria; Linder, Katarzyna; Heni, Martin; Fritsche, Andreas; Preissl, Hubert

2016-01-01

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m2 ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a ‘wanting' and ‘liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity. PMID:26450814

Active clearance of chest drainage catheters reduces retained blood.

PubMed

Sirch, Joachim; Ledwon, Miroslaw; Püski, Tamas; Boyle, Ed M; Pfeiffer, Steffen; Fischlein, Theodor

2016-03-01

Chest tubes are used to clear blood from around the heart and lungs after heart surgery, but they can be obstructed by a blood clot, leading to retained blood syndrome (RBS). We sought to examine the frequency of RBS and associated morbidity, and to determine the influence of a preventative active chest tube clearance (ATC) protocol on these outcomes. A multidisciplinary team developed a simple protocol to institute ATC to preventatively clear chest tubes of clot during the first 24 hours after heart surgery. An extensive educational in-service was performed before universal implementation (phase 1). We retrospectively compared data collected prospectively from 1849 patients before universal implementation (phase 0) with data from 256 patients collected prospectively after universal implementation (phase 2), and then used propensity matching for outcomes assessment. In propensity-matched patients, 19.9% of patients had interventions for RBS (phase 0). After the implementation of ATC (phase 2), the percent of patients with interventions for RBS was reduced to 11.3%, representing a 43% reduction in RBS (P = .0087). These patients had a 33% reduced incidence of postoperative atrial fibrillation from 30% (78 out of 256) in phase 0 to 20% (52 out of 256) in phase 2. (P = .013). ATC is associated with a reduced need for interventions for RBS and postoperative atrial fibrillation. Our findings underscore the importance of maintaining chest tube patency in the early hours after cardiac surgery. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice.

PubMed

Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; Abbring, Suzanne; van der Horst, Hilma; Broersen, Laus M; Willemsen, Linette; Kas, Martien; Garssen, Johan; Kraneveld, Aletta D

2017-01-01

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs. Based on these results, we designed an mTOR-targeting amino acid diet (Active 1 diet) and assessed the effects of dietary interventions with the amino acid diet or a multi-nutrient supplementation diet (Active 2 diet) on autistic-like behavior and mTOR signaling in food allergic mice and in inbred BTBR T+Itpr3tf/J mice. Cow's milk allergic (CMA) or BTBR male mice were fed a Control, Active 1, or Active 2 diet for 7 consecutive weeks. CMA mice showed reduced social interaction and increased self-grooming behavior. Both diets reversed behavioral impairments and inhibited the mTOR activity in the prefrontal cortex and amygdala of CMA mice. In BTBR mice, only Active 1 diet reduced repetitive self-grooming behavior and attenuated the mTOR activity in the prefrontal and somatosensory cortices. The current results suggest that activated mTOR signaling pathway in the brain may be a convergent pathway in the pathogenesis of ASD bridging genetic background and environmental triggers (food allergy) and that mTOR over-activation could serve as a potential therapeutic target for the treatment of ASD. Copyright © 2016. Published by Elsevier Inc.

Muscle strengthening activity associates with reduced all-cause mortality in COPD.

PubMed

Loprinzi, Paul D; Sng, Eveleen; Walker, Jerome F

2017-06-01

Objective Emerging research suggests that aerobic-based physical activity may help to promote survival among chronic obstructive pulmonary disease patients. However, the extent to which engagement in resistance training on survival among chronic obstructive pulmonary disease patients is relatively unknown. Therefore, the purpose of this study was to examine the independent associations of muscle strengthening activities on all-cause mortality among a national sample of U.S. adults with chronic obstructive pulmonary disease. We hypothesize that muscle strengthening activities will be inversely associated with all-cause mortality. Methods Data from the 2003-2006 NHANES were employed, with follow-up through 2011. Aerobic-based physical activity was objectively measured via accelerometry, muscle strengthening activities engagement was assessed via self-report, and chronic obstructive pulmonary disease was assessed via physician-diagnosis. Results Analysis included 385 adults (20 + yrs) with chronic obstructive pulmonary disease, who represent 13.3 million chronic obstructive pulmonary disease patients in the USA. The median follow-up period was 78 months (IQR=64-90), with 82 chronic obstructive pulmonary disease patients dying during this period. For a two muscle strengthening activity sessions/week increase (consistent with national guidelines), chronic obstructive pulmonary disease patients had a 29% reduced risk of all-cause mortality (HR=0.71; 95% CI: 0.51-0.99; P = 0.04). Conclusion Participation in muscle strengthening activities, independent of aerobic-based physical activity and other potential confounders, is associated with greater survival among chronic obstructive pulmonary disease patients.

Seasonal composition and activity of sulfate-reducing prokaryotic communities in seagrass bed sediments

EPA Science Inventory

Sulfate-reducing prokaryotes (SRP) play a key role in the carbon and nutrient cycles of coastal marine, vegetated ecosystems, but the interactions of SRP communities with aquatic plants remain little studied. The abundance, activity, and community composition of SRP was studied i...

Effects of reduced glutathione on acrosin activity in frozen-thawed boar spermatozoa.

PubMed

Estrada, Efrén; Rodríguez-Gil, Joan E; Rivera Del Álamo, Maria M; Peña, Alejandro; Yeste, Marc

2017-02-01

In pigs, acrosin activity in extended semen is correlated with reproductive performance and has recently been identified as a freezability marker. Reduced glutathione (GSH) is known to decrease sperm cryodamage and increase the reproductive performance of frozen-thawed boar spermatozoa. However, the effects of GSH on the acrosin activity of good and poor freezability ejaculates (GFE and PFE, respectively) is yet to be examined. The present study investigated how supplementing cryopreservation media with GSH affected acrosin activity in GFE and PFE, as well as the relationship between acrosin activity and reproductive performance in frozen-thawed boar spermatozoa. In addition, we examined whether the increase in fertility rates and litter sizes observed after the addition of 2mM GSH to cryopreservation extenders was related to acrosin activity. Supplementing freezing media with 2mM GSH partially counteracted the cryopreservation-related decrease in acrosin activity in GFE but not PFE. Acrosin activity was found to be significantly correlated with in vivo reproductive performance of frozen-thawed boar semen. In conclusion, the effects of adding GSH to freezing extenders on the acrosin activity of frozen-thawed boar spermatozoa rely on the intrinsic freezability of the ejaculate. Furthermore, the maintenance of proper acrosin activity could contribute to the increase in reproductive performance mediated by GSH.

Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

PubMed

Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

2014-05-01

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity.

PubMed

Jansen, John A; van Veen, Toon A B; de Jong, Sanne; van der Nagel, Roel; van Stuijvenberg, Leonie; Driessen, Helen; Labzowski, Ronald; Oefner, Carolin M; Bosch, Astrid A; Nguyen, Tri Q; Goldschmeding, Roel; Vos, Marc A; de Bakker, Jacques M T; van Rijen, Harold V M

2012-04-01

Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction expression and increased collagen deposition. We hypothesized that reduced connexin43 (Cx43) expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation of fibrosis in a physiological (aging) and pathophysiological (transverse aortic constriction [TAC]) mouse model. The Cx43(fl/fl) and Cx43(CreER(T)/fl) mice were aged 18 to 21 months or, at the age of 3 months, either TAC or sham operated and euthanized after 16 weeks. Epicardial activation mapping of the right and left ventricles was performed on Langendorff perfused hearts. Sustained ventricular arrhythmias were induced in 0 of 11 aged Cx43(fl/fl) and 10 of 15 Cx43(Cre-ER(T)/fl) mice (P<0.01). Cx43 expression was reduced by half in aged Cx43(CreER(T)/fl) compared with aged Cx43(fl/fl) mice, whereas collagen deposition was significantly increased from 1.1±0.2% to 7.4±1.3%. Aged Cx43(CreER(T)/fl) mice with arrhythmias had significantly higher levels of fibrosis and conduction heterogeneity than aged Cx43(CreER(T)/fl) mice without arrhythmias. The TAC operation significantly increased fibrosis in control compared with sham (4.0±1.2% versus 0.4±0.06%), but this increase was significantly higher in Cx43(CreER(T)/fl) mice (10.8±1.4%). Discoidin domain receptor 2 expression was unchanged, but procollagen peptide I and III expression and collagen type 1α2 mRNA levels were higher in TAC-operated Cx43HZ mice. Reduced cellular coupling results in more excessive collagen deposition during aging or pressure overload in mice due to enhanced fibroblast activity, leading to increased conduction in homogeneity and proarrhythmia.

Promoting Strong Written Communication Skills

NASA Astrophysics Data System (ADS)

Narayanan, M.

2015-12-01

The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

PPAR-γ agonist stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination

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

Sun, Yan; Zheng, Bin; Zhang, Xin-hua

2014-01-10

Highlights: •PPAR-γ increases KLF4 protein level but does not influence KLF4 gene transcription. •The increase of KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. •Pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination. -- Abstract: Peroxisome proliferator activated receptor γ (PPAR-γ) plays important roles in cell cycle regulation, differentiation and apoptosis. Krüppel-like factor 4 (KLF4) modulates vascular smooth muscle cell (VSMC) phenotype. Both KLF4 and PPAR-γ are involved in VSMC proliferation and differentiation. However, the actual relationship between KLF4 and PPAR-γ in VSMCs is not clear. In this study, we found that PPAR-γ agonist pioglitazone increases KLF4more » protein levels but does not influence KLF4 gene transcription. PPAR-γ overexpression increases, while PPAR-γ knockdown reduces KLF4 expression, suggesting that the increase in KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. Further study showed that pioglitazone enhances KLF4 protein stability through reducing KLF4 ubiquitination. Furthermore, we demonstrated that stabilization of KLF4 by pioglitazone was related to the activation of Akt signaling pathway. Taken together, we revealed that PPAR-γ agonist pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination, providing further insights into PPAR-γ and KLF4 in regulating each other’s expression in VSMCs.« less

Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

PubMed

van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

2016-09-01

Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.

Testing a simple control law to reduce broadband frequency harmonic vibrations using semi-active tuned mass dampers

NASA Astrophysics Data System (ADS)

Moutinho, Carlos

2015-05-01

This paper is focused on the control problems related to semi-active tuned mass dampers (TMDs) used to reduce harmonic vibrations, specially involving civil structures. A simplified version of the phase control law is derived and its effectiveness is investigated and evaluated. The objective is to improve the functioning of control systems of this type by simplifying the measurement process and reducing the number of variables involved, making the control system more feasible and reliable. Because the control law is of ON/OFF type, combined with appropriate trigger conditions, the activity of the actuation system may be significantly reduced, which may be of few seconds a day in many practical cases, increasing the durability of the device and reducing its maintenance. Moreover, due to the ability of the control system to command the motion of the inertial mass, the semi-active TMD is relatively insensitive to its initial tuning, resulting in the capability of self-tuning and in the possibility of controlling several vibration modes of a structure over a significant broadband frequency.

Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy.

PubMed

Luo, D; Ren, H; Li, T; Lian, K; Lin, D

2016-03-01

Osteocyte is the orchestrator of bone remolding and decline in osteocyte autophagy is involved in senile osteoporosis. Our results suggested that rapamycin, at least in part by activating osteocyte autophagy, reduced the severity of age-related bone changes in trabecular bone of old male rats. Previous literatures have showed that osteocyte is the orchestrator of bone remolding and age-related decline in osteocyte number is associated with senile osteoporosis. Autophagy is an important cellular protective mechanism which can preserve osteocyte viability and failure of autophagy in osteocyte with age has been linked to senile osteoporosis. The purpose of this study was to explore whether rapamycin, one activator of autophagy, has protective effects on senile osteoporosis through inducing osteocyte autophagy. Fifty-two 24-month-old male Sprague-Dawley (SD) rats were randomly divided into two groups. Rapamycin (1 mg/kg weight/day) or DMSO vehicle control was administered intraperitoneally for 12 weeks. BMD and bone microstructure were determined by Micro-CT. Fluorochrome labeling of the bones was performed to measure the mineral apposition rate (MAR). TRAP staining was performed to evaluate osteoclast number. The plasma levels of bone turnover markers were also analyzed. The effects of rapamycin on osteocyte autophagy were determined by immunohistochemistry, Western blot, and q-PCR. TUNEL was used to determine the prevalence of osteocyte apoptosis. Micro-CT evaluation demonstrated that rapamycin had a protective effect on age-related bone loss in trabecular bone. Besides, rapamycin resulted in an obvious increase of MAR and a decrease of osteoclast number in contrast to the control group. Furthermore, rapamycin also induced autophagy in osteocyte demonstrated by increased LC3-positive osteocyte and increased LC3 turnover. In addition, rats treated with rapamycin exhibited decreased apoptosis of osteocyte determined by TUNEL. These results suggested that rapamycin, at

An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen.

PubMed

Beratis, N G; LaBadie, G U; Hirschhorn, K

1980-03-01

Both the common and a variant isozyme of acid alpha-glucosidase have been purified from a heterozygous placenta with CM-Sephadex, ammonium sulfate precipitation, dialysis, Amicon filtration, affinity chromatography by Sephadex G-100, and DEAE-cellulose chromatography. Three and two activity peaks, from the common and variant isozymes, respectively, were obtained by DEAE-cellulose chromatography using a linear NaCl gradient. The three peaks of activity of the common isozyme were eluted with 0.08, 0.12, and 0.17 M NaCl, whereas the two peaks of the variant, with 0.01 and 0.06 M NaCl. The pH optimum and thermal denaturation at 57 degrees C were the same in all enzyme peaks of both isozymes. Rabbit antiacid alpha-glucosidase antibodies produced against the common isozyme were found to cross-react with both peaks of the variant isozyme. The two isozymes shared antigenic identity and had similar Km's with maltose as substrate. Normal substrate saturation kinetics were observed with the common isozyme when glycogen was the substrate, but the variant produced an S-shaped saturation curve indicating a phase of negative and positive cooperativity at low and high glycogen concentrations, respectively. The activity of the variant was only 8.6% and 19.2% of the common isozyme when assayed with nonsaturating and saturating concentrations of glycogen, respectively. A similar rate of hydrolysis of isomaltose by both isozymes was found indicating that the reduced catalytic activity of the variant isozyme toward glycogen is not the result of a reduced ability of this enzyme to cleave the alpha-1,6 linkages of glycogen.

An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen.

PubMed Central

Beratis, N G; LaBadie, G U; Hirschhorn, K

1980-01-01

Both the common and a variant isozyme of acid alpha-glucosidase have been purified from a heterozygous placenta with CM-Sephadex, ammonium sulfate precipitation, dialysis, Amicon filtration, affinity chromatography by Sephadex G-100, and DEAE-cellulose chromatography. Three and two activity peaks, from the common and variant isozymes, respectively, were obtained by DEAE-cellulose chromatography using a linear NaCl gradient. The three peaks of activity of the common isozyme were eluted with 0.08, 0.12, and 0.17 M NaCl, whereas the two peaks of the variant, with 0.01 and 0.06 M NaCl. The pH optimum and thermal denaturation at 57 degrees C were the same in all enzyme peaks of both isozymes. Rabbit antiacid alpha-glucosidase antibodies produced against the common isozyme were found to cross-react with both peaks of the variant isozyme. The two isozymes shared antigenic identity and had similar Km's with maltose as substrate. Normal substrate saturation kinetics were observed with the common isozyme when glycogen was the substrate, but the variant produced an S-shaped saturation curve indicating a phase of negative and positive cooperativity at low and high glycogen concentrations, respectively. The activity of the variant was only 8.6% and 19.2% of the common isozyme when assayed with nonsaturating and saturating concentrations of glycogen, respectively. A similar rate of hydrolysis of isomaltose by both isozymes was found indicating that the reduced catalytic activity of the variant isozyme toward glycogen is not the result of a reduced ability of this enzyme to cleave the alpha-1,6 linkages of glycogen. Images Fig. 2 Fig. 4 Fig. 6 PMID:6770674

Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine.

PubMed

Ares-Santos, S; Granado, N; Oliva, I; O'Shea, E; Martin, E D; Colado, M I; Moratalla, R

2012-02-01

Methamphetamine (METH) is a potent, highly addictive psychostimulant consumed worldwide. In humans and experimental animals, repeated exposure to this drug induces persistent neurodegenerative changes. Damage occurs primarily to dopaminergic neurons, accompanied by gliosis. The toxic effects of METH involve excessive dopamine (DA) release, thus DA receptors are highly likely to play a role in this process. To define the role of D(1) receptors in the neurotoxic effects of METH we used D(1) receptor knock-out mice (D(1)R(-/-)) and their WT littermates. Inactivation of D(1)R prevented METH-induced dopamine fibre loss and hyperthermia, and increases in gliosis and pro-inflammatory molecules such as iNOS in the striatum. In addition, D(1)R inactivation prevented METH-induced loss of dopaminergic neurons in the substantia nigra. To explore the relationship between hyperthermia and neurotoxicity, METH was given at high ambient temperature (29 °C). In this condition, D(1)R(-/-) mice developed hyperthermia following drug delivery and the neuroprotection provided by D(1)R inactivation at 23 °C was no longer observed. However, reserpine, which empties vesicular dopamine stores, blocked hyperthermia and strongly potentiated dopamine toxicity in D(1)R(-/-) mice, suggesting that the protection afforded by D(1)R inactivation is due to both hypothermia and higher stored vesicular dopamine. Moreover, electrical stimulation evoked higher DA overflow in D(1)R(-/-) mice as demonstrated by fast scan cyclic voltammetry despite their lower basal DA content, suggesting higher vesicular DA content in D(1)R(-/-) than in WT mice. Altogether, these results indicate that the D(1)R plays a significant role in METH-induced neurotoxicity by mediating drug-induced hyperthermia and increasing the releasable cytosolic DA pool. Copyright © 2011. Published by Elsevier Inc.

Do Productive Activities Reduce Inflammation in Later Life? Multiple Roles, Frequency of Activities, and C-Reactive Protein

PubMed Central

Kim, Seoyoun; Ferraro, Kenneth F.

2014-01-01

Purpose of the Study: The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. Design and Methods: The study uses a representative survey of adults aged 57–85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Results: Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Implications: Productive activities—and frequent volunteering in particular—may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. PMID:23969258

Do productive activities reduce inflammation in later life? Multiple roles, frequency of activities, and C-reactive protein.

PubMed

Kim, Seoyoun; Ferraro, Kenneth F

2014-10-01

The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. The study uses a representative survey of adults aged 57-85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Productive activities-and frequent volunteering in particular-may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

PubMed

Lujan, Heidi L; Palani, Gurunanthan; Chen, Ying; Peduzzi, Jean D; Dicarlo, Stephen E

2009-05-01

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).

Strong Cosmic Censorship

NASA Astrophysics Data System (ADS)

Isenberg, James

2017-01-01

The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

Effect of Lead stress on phosphatase activity and reducing power assay of Triticum aestivum.

PubMed

Gubrelay, U; Agnihotri, R K; Shrotriya, S; Sharma, R

2015-06-24

Lead (Pb) is a highly toxic heavy metal for both plants and animals; the environment is increasingly polluted with heavy metals and reduces crop productivity. Plants possess homeostatic mechanisms that allow them to keep correct concentrations of essential metal ions in cellular compartments and to minimize the damaging effects of an excess of nonessential ones. One of their adverse effects on plants are the generation of harmful active oxygen species, leading to oxidative stress and the antioxidative activity seems to be of fundamental importance for adaptive response of plant against environmental stress. The present study explores the effects of lead (soil treated twice/ week) with (10, 30 and 60 mM) on the specific activities of phosphatases which might lead to reducing power assay in (Triticum aestivum PBW344) seedling. A significant decrease in the redox potential of shoot compared to root was observed at the similar concentration of lead. A similar trend on leaves was also noted. Acid and alkaline phosphatase activities were significantly higher in roots than in shoot at all the three concentration of lead i.e. 10, 30 and 60 mM, compared to controls. The above mentioned changes were more pronounced at 60 mM concentration of lead than two other concentrations. These results lead us to suggest that increased lead concentration in soil might lead to adverse effects on plant growth and phosphatase activities.

Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin-Angiotensin System

DTIC Science & Technology

2015-10-01

patients, there is little evidence for a role of ACE2/A( 1 -7)/Mas axis, only a solitary assessment showing decreased ACE2 levels in the CSF of MS...project? Major Goals (Year 1 ): 1 : Measure levels of RAS components in the spinal cord of mice with EAE (animal model of MS) prior to, and at multiple...AWARD NUMBER: W81XWH-14- 1 -0523 TITLE: Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

PubMed Central

Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

2012-01-01

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction

Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu

2016-07-15

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduced Activity of AMP-Activated Protein Kinase Protects against Genetic Models of Motor Neuron Disease

PubMed Central

Lim, M. A.; Selak, M. A.; Xiang, Z.; Krainc, D.; Neve, R. L.; Kraemer, B. C.; Watts, J. L.

2012-01-01

A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease. PMID:22262909

Active-site copper reduction promotes substrate binding of fungal lytic polysaccharide monooxygenase and reduces stability.

PubMed

Kracher, Daniel; Andlar, Martina; Furtmüller, Paul G; Ludwig, Roland

2018-02-02

Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-containing enzymes that oxidatively degrade insoluble plant polysaccharides and soluble oligosaccharides. Upon reductive activation, they cleave the substrate and promote biomass degradation by hydrolytic enzymes. In this study, we employed LPMO9C from Neurospora crassa , which is active toward cellulose and soluble β-glucans, to study the enzyme-substrate interaction and thermal stability. Binding studies showed that the reduction of the mononuclear active-site copper by ascorbic acid increased the affinity and the maximum binding capacity of LPMO for cellulose. The reduced redox state of the active-site copper and not the subsequent formation of the activated oxygen species increased the affinity toward cellulose. The lower affinity of oxidized LPMO could support its desorption after catalysis and allow hydrolases to access the cleavage site. It also suggests that the copper reduction is not necessarily performed in the substrate-bound state of LPMO. Differential scanning fluorimetry showed a stabilizing effect of the substrates cellulose and xyloglucan on the apparent transition midpoint temperature of the reduced, catalytically active enzyme. Oxidative auto-inactivation and destabilization were observed in the absence of a suitable substrate. Our data reveal the determinants of LPMO stability under turnover and non-turnover conditions and indicate that the reduction of the active-site copper initiates substrate binding. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Reduced ITPase activity and favorable IL28B genetic variant protect against ribavirin-induced anemia in interferon-free regimens.

PubMed

Vasanthakumar, Aparna; Davis, Justin W; Abunimeh, Manal; Söderholm, Jonas; Zha, Jiuhong; Dumas, Emily O; Cohen, Daniel E; Waring, Jeffrey F; Lagging, Martin

2018-01-01

Genetic variants of inosine triphosphatase (ITPA) that confer reduced ITPase activity are associated with protection against ribavirin(RBV)-induced hemolytic anemia in peginterferon(IFN)/RBV-based treatment of hepatitis C virus (HCV). Patients with reduced ITPase activity showed improved treatment efficacy when treated with IFN/RBV. In addition, a genetic polymorphism near the IL28B gene is associated with an improved response to IFN/RBV treatment. RBV has been an important component of IFN-containing regimens, and is currently recommended in combination with several IFN-free regimens for treatment of harder to cure HCV infections. To evaluate whether genetic variations that reduce ITPase activity impact RBV-induced anemia in IFN-free/RBV regimens. In this study, genetic analyses were conducted in the PEARL-IV trial to investigate the effect of activity-reducing ITPA variants as well as IL28B polymorphism on anemia, platelet (PLT) counts, and virologic response in HCV genotype1a-infected patients treated with the direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir±RBV. Reduction in ITPase activity and homozygosity for the IL28Brs12979860 CC genotype protected against RBV-induced anemia. In patients receiving RBV, reduced ITPase activity was associated with reduced plasma RBV concentration and higher PLT counts. ITPase activity had no impact on response to DAA treatment, viral kinetics, or baseline IP-10 levels. Our study demonstrates that genetics of ITPA and IL28B may help identify patients protected from RBV-induced anemia when treated with IFN-free regimens. Our work demonstrates for the first time that IL28B genetics may also have an impact on RBV-induced anemia. This may be of particular significance in patients with difficult-to-cure HCV infections, such as patients with decompensated cirrhosis where RBV-containing regimens likely will continue to be recommended.

Anethole potentiates dodecanol's fungicidal activity by reducing PDR5 expression in budding yeast.

PubMed

Fujita, Ken-Ichi; Ishikura, Takayuki; Jono, Yui; Yamaguchi, Yoshihiro; Ogita, Akira; Kubo, Isao; Tanaka, Toshio

2017-02-01

trans-Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum and a weaker antimicrobial potency than other available antibiotics. When combined with polygodial, nagilactone E, and n-dodecanol, anethole has been shown to exhibit synergistic antifungal activity against a budding yeast, Saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, Candida albicans. However, the mechanism underlying this synergistic effect of anethole has not been characterized. We studied this mechanism using dodecanol-treated S. cerevisiae cells and focusing on genes related to multidrug efflux. Although dodecanol transiently reduced the number of colony forming units, this recovered to levels similar to those of untreated cells with continued incubation beyond 24h. Reverse transcription polymerase chain reaction analysis revealed overexpression of an ATP-binding cassette (ABC) transporter gene, PDR5, in addition to a slight increase in PDR11, PDR12, and PDR15 transcriptions in dodecanol-treated cells. In the presence of anethole, these effects were attenuated and the fungicidal activity of dodecanol was extended. Dodecanol showed longer lasting fungicidal activity against a Δpdr5. In addition, Δpdr3 and Δlge1, lack transcription factors of PDR5 and PDR3, were partly and completely susceptible to dodecanol, respectively. Furthermore, combination of anethole with fluconazole was also found to exhibit synergy on C. albicans. These results indicated that although anethole reduced the transcription of several transporters, PDR5 expression was particularly relevant to dodecanol efflux. Anethole is expected to be a promising candidate drug for the inhibition of efflux by reducing the transcription of several ABC transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

Highly multireferenced arynes studied with large active spaces using two-electron reduced density matrices.

PubMed

Greenman, Loren; Mazziotti, David A

2009-05-14

Using the active-space two-electron reduced density matrix (2-RDM) method, which scales polynomially with the size of the active space [G. Gidofalvi and D. A. Mazziotti, J. Chem. Phys. 129, 134108 (2008)], we were able to use active spaces as large as 24 electrons in 24 orbitals in computing the ground-state energies and properties of highly multireferenced arynes. Because the conventional complete-active-space self-consistent-field (CASSCF) method scales exponentially with the size of the active space, its application to arynes was mainly limited to active spaces of 12 electrons in 12 orbitals. For these smaller active spaces the active-space 2-RDM method accurately reproduces the results of CASSCF. However, we show that the larger active spaces are necessary for describing changes in energies and properties with aryne chain length such as the emergence of polyradical character. Furthermore, the addition of further electron correlation by multireference perturbation theory is demonstrated to be inadequate for removing the limitations of the smaller active spaces.

Ceruloplasmin reduces the adhesion and scavenges superoxide during the interaction of activated polymorphonuclear leukocytes with endothelial cells.

PubMed Central

Broadley, C.; Hoover, R. L.

1989-01-01

The plasma protein, ceruloplasmin, has been implicated as an anti-inflammatory agent, although this property has not been demonstrated unequivocally in vivo. The role of this protein in an in vitro system of cultured endothelial cells and polymorphonuclear leukocytes (PMNs) was investigated. One of the initial steps in an inflammatory response is increased adhesion between PMNs and the endothelial lining of the blood vessels. The results showed that ceruloplasmin interferes with this process and reduces the number of phorbol myristate acetate-activated leukocytes that adhere to endothelium. Preincubation of either the activated PMNs or the endothelium with ceruloplasmin did not produce the same results, suggesting that the continuous presence of ceruloplasmin is required. During attachment PMNs become activated and release a variety of substances, including toxic oxygen species such as superoxide and hydrogen peroxide. In the in vitro system used in this study no injury occurred to the endothelial cells, as measured by 51Cr release, when activated PMNs were added with ceruloplasmin. The data show that ceruloplasmin reduced, in a dose dependent manner, the levels of superoxide produced by the activated PMNs, further supporting ceruloplasmin's previously reported role as a scavenger of superoxide. Ceruloplasmin also reduced the levels of superoxide when activated PMNs were in contact with endothelial cells. Although ceruloplasmin interfered with the copper-dependent scavenger enzyme, superoxide dismutase (SOD), in a cell-free system, ceruloplasmin had no effect on SOD in intact endothelial cells. These results suggest that ceruloplasmin may act as an anti-inflammatory agent by reducing the number of PMNs attaching to endothelium and by acting as an extracellular scavenger of superoxide. PMID:2552811

Regulating intestinal function to reduce atherogenic lipoproteins.

PubMed

Hussain, M Mahmood; Leung, Tung Ming; Zhou, Liye; Abu-Merhi, Sarah

2013-08-01

Significant knowledge regarding different molecules involved in the transport of dietary fat into the circulation has been garnered. Studies point to the possibility that accumulation of intestine-derived lipoproteins in the plasma could contribute to atherosclerosis. This article provides a brief overview of dietary lipid metabolism and studies in mice supporting the hypothesis that intestinal lipoproteins contribute to atherosclerosis. Deficiencies in lipoprotein lipase and Gpihbp1, and overexpression of heparanse in mice, are associated with increases in atherosclerosis, suggesting that defects in catabolism of larger lipoproteins in the plasma contribute to atherosclerosis. Furthermore, inositol-requiring enzyme 1β-deficient mice that produce more intestinal lipoproteins also develop more atherosclerosis. Thus, increases in plasma intestinal lipoproteins due to either overproduction or reduced catabolism result in augmented atherosclerosis. Intestinal lipoproteins tend to adhere strongly to subendothelial proteoglycans, elicit an inflammatory response by endothelial cells and activate macrophages, contributing to the initiation and progression of the disease. Thus, molecules that reduce intestinal lipid absorption can be useful in lowering atherosclerosis.

Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

PubMed

Pinsky, C; Dua, A K; LaBella, F S

1982-07-15

Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses.

PubMed

Pizzagalli, D; Lehmann, D; Gianotti, L; Koenig, T; Tanaka, H; Wackermann, J; Brugger, P

2000-12-22

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

Antioxidant activity of spice extracts in a liposome system and in cooked pork patties and the possible mode of action.

PubMed

Kong, Baohua; Zhang, Huiyun; Xiong, Youling L

2010-08-01

Three experiments were conducted to assess the antioxidant efficacy of spice extracts in cooked meat. In experiment 1, antioxidant activity of 13 common spice extracts was screened in a liposome system. Six of the extracts (clove, rosemary, cassia bark, liquorice, nutmeg, and round cardamom), identified to have the greatest total phenolic contents, were strongly inhibitory of TBARS formation. In experiment 2, 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferric-reducing power, and metal chelation of these six spice extracts were evaluated. Clove exhibited the greatest reducing power, and all had strong DPPH scavenging activity. In experiment 3, clove, rosemary, and cassia bark extracts were further tested for in situ antioxidant efficacy. Cooked pork patties containing these spice extracts had markedly reduced TBARS formation and off-flavour scores but a more stable red colour, during storage. The results demonstrated strong potential of spice extracts as natural antioxidants in cooked pork products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Beta-glucuronidase activity in dried blood spots: Reduced technique with biochemical parameters determined.

PubMed

Cé, Jaqueline; Rodrigues, Melissa Tôrres; Käfer, Eduarda Tassoni; da Costa Moraes, Vitória; Coelho, Janice Carneiro

2017-12-01

Mucopolysaccharidoses (MPS) occur due to deficiency in the activity of enzymes that catalyze the breakdown of glycosaminoglycans. MPS VII is caused by deficiency of the beta-glucuronidase enzyme (GUSB). This study aimed to enhance the technique to measure GUSB activity by reducing the amount of reagents and the size of the DBS, as well as to determine some biochemical parameters of enzyme of healthy individuals. The measurement of GUSB in 3 and 1.2mm DBS (with reagents reduced 2.5- and fourfold) was correlated and the precision of the technique was tested. Optimal pH, Km and Vmax, and thermostability parameters were determined and time and temperature of sample storage were established. The correlations among the techniques were significant. Although the correlation coefficient was similar, fourfold reduction was selected. pH4.4 had the highest enzyme activity. GUSB's Km was 1.25mM, while Vmax was 594.48nmol/h/mL. After pre-incubation of the sample at 60°C, its activity dropped from 100% to 15.8% at 120min. GUSB activity significantly decreased after 45days of storage at 4, 25, and 37°C. This research allowed a previously described technique for MPS VII diagnosis to be adapted for smaller amounts of sample and reagents. That will facilitate the use of smaller amounts of samples, which may be used for other techniques and to save material. Given the importance of early MPS VII diagnosis due to the severity of the disease, using reliable diagnostic techniques in DBS is essential. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.

PubMed

Morgan, V; Pickens, D; Gautam, S; Kessler, R; Mertz, H

2005-05-01

Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

Low temperature and binding to food components inhibit the antibacterial activity of carvacrol against Listeria monocytogenes in steak tartare.

PubMed

Veldhuizen, Edwin J A; Creutzberg, T Olaf; Burt, Sara A; Haagsman, Henk P

2007-09-01

Carvacrol is a major component of thyme and oregano essential oils and has potential uses as a food preservative. The effect of carvacrol on the growth of Listeria monocytogenes was investigated in vitro and in steak tartare. Carvacrol had strong antilisterial activity in growth medium (MIC = 1.6 mM), but no effect was observed when carvacrol was tested in steak tartare. There were two reasons for this reduced activity: the antilisterial activity of carvacrol was strongly reduced at lower temperatures (10 versus 30 degrees C), and the presence of food components interfered with the activity of carvacrol. Both bovine serum albumin and egg yolk inhibited carvacrol activity at > 0.2% (wt/vol) in growth medium. For the first time, carvacrol was found to bind to albumin, suggesting that the reduced antilisterial activity of carvacrol in foods such as dairy products and uncooked meats is the result of fewer free unbound carvacrol molecules available to interact with bacteria.

Glutathione and Glutaredoxin Act as a Backup of Human Thioredoxin Reductase 1 to Reduce Thioredoxin 1 Preventing Cell Death by Aurothioglucose*

PubMed Central

Du, Yatao; Zhang, Huihui; Lu, Jun; Holmgren, Arne

2012-01-01

Thioredoxin reductase 1 (TrxR1) in cytosol is the only known reductant of oxidized thioredoxin 1 (Trx1) in vivo so far. We and others found that aurothioglucose (ATG), a well known active-site inhibitor of TrxR1, inhibited TrxR1 activity in HeLa cell cytosol but had no effect on the viability of the cells. Using a redox Western blot analysis, no change was observed in redox state of Trx1, which was mainly fully reduced with five sulfhydryl groups. In contrast, auranofin killed cells and oxidized Trx1, also targeting mitochondrial TrxR2 and Trx2. Combining ATG with ebselen gave a strong synergistic effect, leading to Trx1 oxidation, reactive oxygen species accumulation, and cell death. We hypothesized that there should exist a backup system to reduce Trx1 when only TrxR1 activity was lost. Our results showed that physiological concentrations of glutathione, NADPH, and glutathione reductase reduced Trx1 in vitro and that the reaction was strongly stimulated by glutaredoxin1. Simultaneous depletion of TrxR activity by ATG and glutathione by buthionine sulfoximine led to overoxidation of Trx1 and loss of HeLa cell viability. In conclusion, the glutaredoxin system and glutathione have a backup role to keep Trx1 reduced in cells with loss of TrxR1 activity. Monitoring the redox state of Trx1 shows that cell death occurs when Trx1 is oxidized, followed by general protein oxidation catalyzed by the disulfide form of thioredoxin. PMID:22977247

77 FR 16131 - Establishing a White House Council on Strong Cities, Strong Communities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... Order 13602 of March 15, 2012 Establishing a White House Council on Strong Cities, Strong Communities By... inclusive, it is hereby ordered as follows: Section 1. Policy. Cities, towns, and regions across our Nation... collaboration, my Administration established the Strong Cities, Strong Communities (SC2) pilot initiative. By...

Enhanced antimicrobial activities of silver-nanoparticle-decorated reduced graphene nanocomposites against oral pathogens.

PubMed

Peng, Jian-Min; Lin, Jia-Cheng; Chen, Zhuo-Yu; Wei, Meng-Chao; Fu, Yuan-Xiang; Lu, Shu-Shen; Yu, Dong-Sheng; Zhao, Wei

2017-02-01

As a means of capitalizing on the synergistic properties between reduced graphene nanosheets (R-GNs) and silver nanoparticles (AgNPs), an efficient and convenient chemical reduction method was used to prepare silver-nanoparticle-decorated reduced graphene nanocomposites (R-GNs/Ag). The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy, which confirmed the loading of well-dispersed silver nanoparticles on reduced graphene sheets. Their antimicrobial activities against oral pathogens such as Candida albicans, Lactobacillus acidophilus, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were investigated by MIC determination, the counting of colony-forming units (CFU), agar diffusion tests, and growth curve observation. Compared with pure R-GNs and AgNPs, R-GNs/Ag composites exhibited enhanced antimicrobial properties owing to highly dispersed AgNPs on R-GNs. Copyright © 2016 Elsevier B.V. All rights reserved.

Active and hibernating turbulence in drag-reducing plane Couette flows

NASA Astrophysics Data System (ADS)

Pereira, Anselmo S.; Mompean, Gilmar; Thais, Laurent; Soares, Edson J.; Thompson, Roney L.

2017-08-01

In this paper we analyze the active and hibernating turbulence in drag-reducing plane Couette flows using direct numerical simulations of the viscoelastic finitely extensible nonlinear elastic model with the Peterlin approximation fluids. The polymer-turbulence interactions are studied from an energetic standpoint for a range of Weissenberg numbers (from 2 up to 30), fixing the Reynolds number based on the plate velocities at 4000, the viscosity ratio at 0.9, and the maximum polymer molecule extensibility at 100. The qualitative picture that emerges from this investigation is a cyclic mechanism of energy exchange between the polymers and turbulence that drives the flow through an oscillatory behavior.

Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

PubMed

Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

2017-06-01

Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition

PubMed Central

Towers, Albert E; Oelschlager, Maci L.; Patel, Jay; Gainey, Stephen J.; McCusker, Robert; Freund, Gregory G.

2017-01-01

Background Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β is regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Methods Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24 hours or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. Results A 24 h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24 h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Conclusions Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. PMID:28521881

N-ACETYLCYSTEINE REDUCES DISEASE ACTIVITY BY BLOCKING MTOR IN T CELLS OF LUPUS PATIENTS

PubMed Central

Lai, Zhi-Wei; Hanczko, Robert; Bonilla, Eduardo; Caza, Tiffany N.; Clair, Brandon; Bartos, Adam; Miklossy, Gabriella; Jimah, John; Doherty, Edward; Tily, Hajra; Francis, Lisa; Garcia, Ricardo; Dawood, Maha; Yu, Jianghong; Ramos, Irene; Coman, Ioana; Faraone, Stephen V.; Phillips, Paul E.; Perl, Andras

2012-01-01

Background Systemic lupus erythematosus (SLE) patients exhibit T-cell dysfunction which can be regulated through the mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione. Therefore, the safety, tolerance, and efficacy of glutathione-precursor N-acetylcysteine (NAC) were examined in this randomized double-blind placebo-controlled study. Methods 36 SLE patients received daily placebo or 1.2 g, 2.4 g or 4.8 g of NAC. Disease activity was monthly evaluated by BILAG, SLEDAI and fatigue assessment scale (FAS) before, during, and after 3-month treatment. Δψm and mTOR were assessed by flow cytometry. 42 healthy subjects matched for patients’ age, gender, and ethnicity were studied as controls. Results NAC was tolerated by all patients up to 2.4 g/day while 33% of those receiving 4.8 g/day had reversible nausea. Placebo or 1.2 g/day NAC did not influence disease activity. Considered together, 2.4 g and 4.8 g NAC reduced: 1) SLEDAI after 1 month (p=0.0007), 2 months (p=0.0009), 3 months (p=0.0030) and 4 months (p=0.0046); 2) BILAG after 1 month (p=0.029) and 3 months (p=0.0009); and 3) FAS after 2 months (p=0.002) and 3 months (p=0.004). NAC increased Δψm (p=0.0001) in all T cells, it profoundly reduced mTOR activity (p=0.0001), enhanced apoptosis (p=0.0004) and reversed expansion of CD4−/CD8− T cells (1.35 ± 0.12-fold; p=0.008), stimulated Foxp3 expression in CD4+/CD25+ T cells (p=0.045), and reduced anti-DNA production (p=0.049). Conclusions This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes. PMID:22549432

Potential association of reduced cholinesterase activity with Trypanosoma evansi pathogenesis in buffaloes.

PubMed

Singh, Shanker K; Singh, Vivek K; Yadav, Brajesh K; Nakade, Udayraj P; Kumari, Priyambada; Srivastava, Mukesh K; Sharma, Abhishek; Choudhary, Soumen; Swain, Dilip; Garg, Satish K

2016-07-30

The present study aimed to investigate the association of cholinesterase activity with trypanosomosis in buffaloes. Thirty-three clinical cases of trypanosomosis in water buffaloes, found positive for trypomastigotes of T. evansi on blood smear examination, were divided into two groups based on clinical manifestations. Twenty diseased buffaloes revealing only common clinical signs were allocated to Group I, while the remaining 13 buffaloes showing common clinical manifestations along with neurological disturbances were allocated to Group II. Twelve clinically healthy buffaloes, free from any haemoprotozoa infection, were kept as healthy control (Group III). Blood samples were collected from buffaloes of all three groups to determine serum cholinesterase activity. Compared to buffaloes of healthy control group, cholinesterase activity in T. evansi-infected buffaloes of Group I and II was significantly (P<0.001) lower. However, no significant difference was observed in cholinesterase activity between the T. evansi-infected buffaloes exhibiting neurological disorders and no neurological disorders. Summing up, reduced cholinesterase activity seems to be associated with the pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes possibly by evading immune response. Further studies are warranted on association of cholinesterase activity in T. evansi-infected buffaloes with neurological disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

PubMed

Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

PubMed

Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick

2016-11-01

The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P < .05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P < .01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P < .01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P < .01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Activation of biceps femoris long head reduces tibiofemoral anterior shear force and tibial internal rotation torque in healthy subjects

PubMed Central

Azmi, Nur Liyana; Ding, Ziyun; Xu, Rui

2018-01-01

The anterior cruciate ligament (ACL) provides resistance to tibial internal rotation torque and anterior shear at the knee. ACL deficiency results in knee instability. Optimisation of muscle contraction through functional electrical stimulation (FES) offers the prospect of mitigating the destabilising effects of ACL deficiency. The hypothesis of this study is that activation of the biceps femoris long head (BFLH) reduces the tibial internal rotation torque and the anterior shear force at the knee. Gait data of twelve healthy subjects were measured with and without the application of FES and taken as inputs to a computational musculoskeletal model. The model was used to investigate the optimum levels of BFLH activation during FES gait in reducing the anterior shear force to zero. This study found that FES significantly reduced the tibial internal rotation torque at the knee during the stance phase of gait (p = 0.0322) and the computational musculoskeletal modelling revealed that a mean BFLH activation of 20.8% (±8.4%) could reduce the anterior shear force to zero. At the time frame when the anterior shear force was zero, the internal rotation torque was reduced by 0.023 ± 0.0167 Nm/BW, with a mean 188% reduction across subjects (p = 0.0002). In conclusion, activation of the BFLH is able to reduce the tibial internal rotation torque and the anterior shear force at the knee in healthy control subjects. This should be tested on ACL deficient subject to consider its effect in mitigating instability due to ligament deficiency. In future clinical practice, activating the BFLH may be used to protect ACL reconstructions during post-operative rehabilitation, assist with residual instabilities post reconstruction, and reduce the need for ACL reconstruction surgery in some cases. PMID:29304102

Activation of biceps femoris long head reduces tibiofemoral anterior shear force and tibial internal rotation torque in healthy subjects.

PubMed

Azmi, Nur Liyana; Ding, Ziyun; Xu, Rui; Bull, Anthony M J

2018-01-01

The anterior cruciate ligament (ACL) provides resistance to tibial internal rotation torque and anterior shear at the knee. ACL deficiency results in knee instability. Optimisation of muscle contraction through functional electrical stimulation (FES) offers the prospect of mitigating the destabilising effects of ACL deficiency. The hypothesis of this study is that activation of the biceps femoris long head (BFLH) reduces the tibial internal rotation torque and the anterior shear force at the knee. Gait data of twelve healthy subjects were measured with and without the application of FES and taken as inputs to a computational musculoskeletal model. The model was used to investigate the optimum levels of BFLH activation during FES gait in reducing the anterior shear force to zero. This study found that FES significantly reduced the tibial internal rotation torque at the knee during the stance phase of gait (p = 0.0322) and the computational musculoskeletal modelling revealed that a mean BFLH activation of 20.8% (±8.4%) could reduce the anterior shear force to zero. At the time frame when the anterior shear force was zero, the internal rotation torque was reduced by 0.023 ± 0.0167 Nm/BW, with a mean 188% reduction across subjects (p = 0.0002). In conclusion, activation of the BFLH is able to reduce the tibial internal rotation torque and the anterior shear force at the knee in healthy control subjects. This should be tested on ACL deficient subject to consider its effect in mitigating instability due to ligament deficiency. In future clinical practice, activating the BFLH may be used to protect ACL reconstructions during post-operative rehabilitation, assist with residual instabilities post reconstruction, and reduce the need for ACL reconstruction surgery in some cases.

Reduced order modeling and active flow control of an inlet duct

NASA Astrophysics Data System (ADS)

Ge, Xiaoqing

Many aerodynamic applications require the modeling of compressible flows in or around a body, e.g., the design of aircraft, inlet or exhaust duct, wind turbines, or tall buildings. Traditional methods use wind tunnel experiments and computational fluid dynamics (CFD) to investigate the spatial and temporal distribution of the flows. Although they provide a great deal of insight into the essential characteristics of the flow field, they are not suitable for control analysis and design due to the high physical/computational cost. Many model reduction methods have been studied to reduce the complexity of the flow model. There are two main approaches: linearization based input/output modeling and proper orthogonal decomposition (POD) based model reduction. The former captures mostly the local behavior near a steady state, which is suitable to model laminar flow dynamics. The latter obtains a reduced order model by projecting the governing equation onto an "optimal" subspace and is able to model complex nonlinear flow phenomena. In this research we investigate various model reduction approaches and compare them in flow modeling and control design. We propose an integrated model-based control methodology and apply it to the reduced order modeling and active flow control of compressible flows within a very aggressive (length to exit diameter ratio, L/D, of 1.5) inlet duct and its upstream contraction section. The approach systematically applies reduced order modeling, estimator design, sensor placement and control design to improve the aerodynamic performance. The main contribution of this work is the development of a hybrid model reduction approach that attempts to combine the best features of input/output model identification and POD method. We first identify a linear input/output model by using a subspace algorithm. We next project the difference between CFD response and the identified model response onto a set of POD basis. This trajectory is fit to a nonlinear

6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of NFκB activation in airway epithelial cells.

PubMed

Kurakula, Kondababu; Hamers, Anouk A; van Loenen, Pieter; de Vries, Carlie J M

2015-06-19

Mucus hypersecretion and excessive cytokine synthesis is associated with many of the pathologic features of chronic airway diseases such as asthma. 6-Mercaptopurine (6-MP) is an immunosuppressive drug that is widely used in several inflammatory disorders. Although 6-MP has been used to treat asthma, its function and mechanism of action in airway epithelial cells is unknown. Confluent NCI-H292 and MLE-12 epithelial cells were pretreated with 6-MP followed by stimulation with TNFα or PMA. mRNA levels of cytokines and mucins were measured by RT-PCR. Western blot analysis was performed to assess the phosphorylation of IκBα and luciferase assays were performed using an NFκB reporter plasmid to determine NFκB activity. Periodic Acid Schiff staining was used to assess the production of mucus. 6-MP displayed no effect on cell viability up to a concentration of 15 μM. RT-PCR analysis showed that 6-MP significantly reduces TNFα- and PMA-induced expression of several proinflammatory cytokines in NCI-H292 and MLE-12 cells. Consistent with this, we demonstrated that 6-MP strongly inhibits TNFα-induced phosphorylation of IκBα and thus attenuates NFκB luciferase reporter activity. In addition, 6-MP decreases Rac1 activity in MLE-12 cells. 6-MP down-regulates gene expression of the mucin Muc5ac, but not Muc2, through inhibition of activation of the NFκB pathway. Furthermore, PMA- and TNFα-induced mucus production, as visualized by Periodic Acid Schiff (PAS) staining, is decreased by 6-MP. Our data demonstrate that 6-MP inhibits Muc5ac gene expression and mucus production in airway epithelial cells through inhibition of the NFκB pathway, and 6-MP may represent a novel therapeutic target for mucus hypersecretion in airway diseases.

Active shielding to reduce low frequency disturbances in direct current near biomagnetic measurements

NASA Astrophysics Data System (ADS)

Platzek, D.; Nowak, H.; Giessler, F.; Röther, J.; Eiselt, M.

1999-05-01

Measurements of dc near biomagnetic fields are disturbed by low frequency noise that is not reduced sufficiently by most of the magnetically shielded rooms or gradiometers. For this reason an active shielding system has been developed at the Biomagnetic Center of the University of Jena. This work describes the principle of the active shielding system and demonstrates its properties concerning the attenuation of disturbing fields, frequency range, and some applications in biomedical measurements. We achieved a reduction of external low frequency magnetic fields by more than 50 dB and an attenuation of the field gradient by about 25 dB. This active shielding enables measurements of near dc biomagnetic fields in investigations of periinfarct depolarizations after ischemic stroke and spreading depression in migraine patients.

Aluminum nanostructures with strong visible-range SERS activity for versatile micropatterning of molecular security labels.

PubMed

Lay, Chee Leng; Koh, Charlynn Sher Lin; Wang, Jing; Lee, Yih Hong; Jiang, Ruibin; Yang, Yijie; Yang, Zhe; Phang, In Yee; Ling, Xing Yi

2018-01-03

The application of aluminum (Al)-based nanostructures for visible-range plasmonics, especially for surface-enhanced Raman scattering (SERS), currently suffers from inconsistent local electromagnetic field distributions and/or inhomogeneous distribution of probe molecules. Herein, we lithographically fabricate structurally uniform Al nanostructures which enable homogeneous adsorption of various probe molecules. Individual Al nanostructures exhibit strong local electromagnetic field enhancements, in turn leading to intense SERS activity. The average SERS enhancement factor (EF) for individual nanostructures exceeds 10 4 for non-resonant probe molecules in the visible spectrum. These Al nanostructures also retain more than 70% of their original SERS intensities after one-month storage, displaying superb stability under ambient conditions. We further achieve tunable polarization-dependent SERS responses using anisotropic Al nanostructures, facilitating the design of sophisticated SERS-based security labels. Our micron-sized security label comprises two-tier security features, including a machine-readable hybrid quick-response (QR) code overlaid with a set of ciphertexts. Our work demonstrates the versatility of Al-based structures in low-cost modern chemical nano-analytics and forgery protection.

Dioxin mediates downregulation of the reduced folate carrier transport activity via the arylhydrocarbon receptor signalling pathway

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

Halwachs, Sandra, E-mail: halwachs@vetmed.uni-leipzig.d; Lakoma, Cathleen; Gebhardt, Rolf

2010-07-15

Dioxins such as 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) are common environmental contaminants known to regulate several genes via activation of the transcription factor aryl hydrocarbon receptor (AhR) associated with the development of numerous adverse biological effects. However, comparatively little is known about the molecular mechanisms by which dioxins display their toxic effects in vertebrates. The 5' untranslated region of the hepatocellular Reduced folate carrier (Rfc1; Slc19a1) exhibits AhR binding sites termed dioxin responsive elements (DRE) that have as yet only been found in the promoter region of prototypical TCDD target genes. Rfc1 mediated transport of reduced folates and antifolate drugs such as methotrexatemore » (MTX) plays an essential role in physiological folate homeostasis and MTX cancer chemotherapy. In order to determine whether this carrier represents a target gene of dioxins we have investigated the influence of TCDD on functional Rfc1 activity in rat liver. Pre-treatment of rats with TCDD significantly diminished hepatocellular Rfc1 uptake activity in a time- and dose-dependent manner. In further mechanistic studies we demonstrated that this reduction was due to TCDD-dependent activation of the AhR signalling pathway. We additionally showed that binding of the activated receptor to DRE motifs in the Rfc1 promoter resulted in downregulation of Rfc1 gene expression and reduced carrier protein levels. As downregulation of pivotal Rfc1 activity results in functional folate deficiency associated with an elevated risk of cardiovascular diseases or carcinogenesis, our results indicate that deregulation of this essential transport pathway represents a novel regulatory mechanism how dioxins display their toxic effects through the Ah receptor.« less

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII as the Active Center.

PubMed

Zhang, Wei; Lu, Jun; Gao, Xiaonan; Li, Ping; Zhang, Wen; Ma, Yu; Wang, Hui; Tang, Bo

2018-02-16

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano-metal-organic framework (Cu II -metalated nano-MOF {CuL-[AlOH] 2 } n (MOF-2, H 6 L=mesotetrakis(4-carboxylphenyl)porphyrin)) based on Cu II as the active center for PDT. This MOF-2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF-2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF-2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF-2 as a promising new PDT candidate and anticancer drug. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physical Education Increases Daily Moderate to Vigorous Physical Activity and Reduces Sedentary Time

ERIC Educational Resources Information Center

Mooses, Kerli; Pihu, Maret; Riso, Eva-Maria; Hannus, Aave; Kaasik, Priit; Kull, Merike

2017-01-01

Background: Physical activity (PA) is important to mental and physical health. Physical education (PE) lessons have the potential to increase daily moderate to vigorous PA (MVPA) and reduce sedentary time (SED). We measured MVPA and SED in primary school PE, determined the contribution of PE to daily MVPA and SED, and compared PA on days with and…

Silver nanoparticles anchored reduced graphene oxide for enhanced electrocatalytic activity towards methanol oxidation

NASA Astrophysics Data System (ADS)

Kumar, Sanjeev; Mahajan, Mani; Singh, Rajinder; Mahajan, Aman

2018-02-01

In this report, silver nanoparticles (Ag NPs) anchored reduced graphene oxide (rGO) sheets (rGO/Ag) nanohybrid has been explored as anode material in direct methanol fuel cells (DMFCs). The synthesized rGO/Ag nanohybrid is characterized by XRD, XPS, FTIR spectroscopy and HRTEM techniques. Cyclic voltammograms demonstrate that the rGO/Ag nanohybrid exhibits higher electrocatalytic activity in comparison to rGO sheets for methanol oxidation reaction (MOR). This enhancement is attributed to the synergetic effect produced by the presence of more active sites provided by Ag NPs anchored on a conducting network of large surface area rGO sheets.

On Strong Anticipation

PubMed Central

Stepp, N.; Turvey, M. T.

2009-01-01

We examine Dubois's (2003) distinction between weak anticipation and strong anticipation. Anticipation is weak if it arises from a model of the system via internal simulations. Anticipation is strong if it arises from the system itself via lawful regularities embedded in the system's ordinary mode of functioning. The assumption of weak anticipation dominates cognitive science and neuroscience and in particular the study of perception and action. The assumption of strong anticipation, however, seems to be required by anticipation's ubiquity. It is, for example, characteristic of homeostatic processes at the level of the organism, organs, and cells. We develop the formal distinction between strong and weak anticipation by elaboration of anticipating synchronization, a phenomenon arising from time delays in appropriately coupled dynamical systems. The elaboration is conducted in respect to (a) strictly physical systems, (b) the defining features of circadian rhythms, often viewed as paradigmatic of biological behavior based in internal models, (c) Pavlovian learning, and (d) forward models in motor control. We identify the common thread of strongly anticipatory systems and argue for its significance in furthering understanding of notions such as “internal”, “model” and “prediction”. PMID:20191086

The Effectiveness of Abstinence Education Programs in Reducing Sexual Activity among Youth. The Heritage Foundation Backgrounder.

ERIC Educational Resources Information Center

Rector, Robert

Teenage sexual activity is a major problem confronting the nation and has led to a rising incidence of sexually transmitted diseases, emotional and psychological injuries, and out-of-wedlock childbearing. Abstinence education programs for youth have proven effective in reducing early sexual activity. They can also provide the foundation for…

Sorptive Activity and Hydrophobic Behavior of Aerogels Based on Reduced Graphene Oxide and Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Sultanov, F.; Bakbolat, B.; Daulbaev, Ch.; Urazgalieva, A.; Azizov, Z.; Mansurov, Z.; Tulepov, M.; Pei, S. S.

2017-07-01

A study has been made of the possibility of obtaining three-dimensional porous aerogel structures based on reduced graphene oxide and carbon nanotubes. Carbon nanotubes in the structure of the finished aerogel based on reduced graphene oxide were grown by thermal decomposition of ferrocene into cyclopentadienyl and iron ions which served as the source of carbon and a catalyst respectively. The obtained composite aerogels exhibit high sorptive activity for organic liquids of different densities.

Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo

PubMed Central

Esmaeili, Mohammad A.; Yadav, Shilpi; Gupta, Ravi Kr.; Waggoner, Garrett R.; Deloach, Abigail; Calingasan, Noel Y.; Beal, M. Flint; Kiaei, Mahmoud

2016-01-01

Neuroinflammation, immune reactivity and mitochondrial abnormalities are considered as causes and/or contributors to neuronal degeneration. Peroxisome proliferator-activated receptors (PPARs) regulate both inflammatory and multiple other pathways that are implicated in neurodegeneration. In the present study, we investigated the efficacy of fenofibrate (Tricor), a pan-PPAR agonist that activates PPAR-α as well as other PPARs. We administered fenofibrate to superoxide dismutase 1 (SOD1G93A) mice daily prior to any detectable phenotypes and then animal behavior, pathology and longevity were assessed. Treated animals showed a significant slowing of the progression of disease with weight loss attenuation, enhanced motor performance, delayed onset and survival extension. Histopathological analysis of the spinal cords showed that neuronal loss was significantly attenuated in fenofibrate-treated mice. Mitochondria were preserved as indicated by Cytochrome c immunostaining in the spinal cord, which maybe partly due to increased expression of the PPAR-γ co-activator 1-α. The total mRNA analysis revealed that neuroprotective and anti-inflammatory genes were elevated, while neuroinflammatory genes were down-regulated. This study demonstrates that the activation of PPAR-α action via fenofibrate leads to neuroprotection by both reducing neuroinflammation and protecting mitochondria, which leads to a significant increase in survival in SOD1G93A mice. Therefore, the development of therapeutic strategies to activate PPAR-α as well as other PPARs may lead to new therapeutic agents to slow or halt the progression of amyotrophic lateral sclerosis. PMID:26604138

EPA + DHA supplementation reduces PMN activation in microenvironment of chronic venous leg ulcers: A randomized, double-blind, controlled study.

PubMed

McDaniel, Jodi C; Szalacha, Laura; Sales, Michelle; Roy, Sashwati; Chafee, Scott; Parinandi, Narasimham

2017-08-01

Sustained high levels of activated polymorphonuclear leukocytes (PMNs) and PMN-derived proteases in the microenvironment of chronic venous leg ulcers (CVLUs) are linked to chronic inflammation and delayed healing. Uncontrolled PMN activity eventually destroys newly developed tissue and degrades critical growth factors. The bioactive components of fish oil (n-3 eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have strong inflammation-resolving actions and have been shown to assuage PMN activity, but have not been tested in CVLU patients. This randomized controlled study compared the effectiveness of oral EPA + DHA therapy to a placebo for reducing PMN activation in CVLU microenvironments. At Days 0, 28, and 56, markers of PMNs (CD15) and activated PMNs (CD66b), and levels of PMN-derived proteases human neutrophil elastase and matrix metalloproteinase-8 were measured in CVLU fluid from patients receiving standard compression therapy and (1) EPA + DHA therapy (n = 16) or (2) placebo (n = 19). By Day 56, the EPA + DHA Group had a significantly lower percentage of CD66b+ cells in CVLU fluid compared to Day 0 (p = 0.02) and to Day 28 (p = 0.05). Importantly, there were downward trends in levels of both matrix metalloproteinase-8 and human neutrophil elastase over time in the EPA + DHA Group, which also demonstrated greater reductions in wound area by Day 28 (57% reduction) and Day 56 (76% reduction) than the Control Group (35% and 59%, respectively). Moreover, reductions in wound area had significant negative relationships with CD15+ cells in wound fluid at Days 28 (p = 0.008) and 56 (p < 0.001), and CD66b+ cells at Days 28 (p = 0.04) and 56 (p = 0.009). The collective findings provide supplemental evidence that high levels of activated PMNs in CVLU microenvironments inhibit healing, and suggest that EPA + DHA oral therapy may modulate PMN activity and facilitate healing of CVLUs when added to standard care

Tropical cyclone activity enhanced by Sahara greening and reduced dust emissions during the African Humid Period.

PubMed

Pausata, Francesco S R; Emanuel, Kerry A; Chiacchio, Marc; Diro, Gulilat T; Zhang, Qiong; Sushama, Laxmi; Stager, J Curt; Donnelly, Jeffrey P

2017-06-13

Tropical cyclones (TCs) can have devastating socioeconomic impacts. Understanding the nature and causes of their variability is of paramount importance for society. However, historical records of TCs are too short to fully characterize such changes and paleo-sediment archives of Holocene TC activity are temporally and geographically sparse. Thus, it is of interest to apply physical modeling to understanding TC variability under different climate conditions. Here we investigate global TC activity during a warm climate state (mid-Holocene, 6,000 yBP) characterized by increased boreal summer insolation, a vegetated Sahara, and reduced dust emissions. We analyze a set of sensitivity experiments in which not only solar insolation changes are varied but also vegetation and dust concentrations. Our results show that the greening of the Sahara and reduced dust loadings lead to more favorable conditions for tropical cyclone development compared with the orbital forcing alone. In particular, the strengthening of the West African Monsoon induced by the Sahara greening triggers a change in atmospheric circulation that affects the entire tropics. Furthermore, whereas previous studies suggest lower TC activity despite stronger summer insolation and warmer sea surface temperature in the Northern Hemisphere, accounting for the Sahara greening and reduced dust concentrations leads instead to an increase of TC activity in both hemispheres, particularly over the Caribbean basin and East Coast of North America. Our study highlights the importance of regional changes in land cover and dust concentrations in affecting the potential intensity and genesis of past TCs and suggests that both factors may have appreciable influence on TC activity in a future warmer climate.

Tropical cyclone activity enhanced by Sahara greening and reduced dust emissions during the African Humid Period

NASA Astrophysics Data System (ADS)

Pausata, Francesco S. R.; Emanuel, Kerry A.; Chiacchio, Marc; Diro, Gulilat T.; Zhang, Qiong; Sushama, Laxmi; Stager, J. Curt; Donnelly, Jeffrey P.

2017-06-01

Tropical cyclones (TCs) can have devastating socioeconomic impacts. Understanding the nature and causes of their variability is of paramount importance for society. However, historical records of TCs are too short to fully characterize such changes and paleo-sediment archives of Holocene TC activity are temporally and geographically sparse. Thus, it is of interest to apply physical modeling to understanding TC variability under different climate conditions. Here we investigate global TC activity during a warm climate state (mid-Holocene, 6,000 yBP) characterized by increased boreal summer insolation, a vegetated Sahara, and reduced dust emissions. We analyze a set of sensitivity experiments in which not only solar insolation changes are varied but also vegetation and dust concentrations. Our results show that the greening of the Sahara and reduced dust loadings lead to more favorable conditions for tropical cyclone development compared with the orbital forcing alone. In particular, the strengthening of the West African Monsoon induced by the Sahara greening triggers a change in atmospheric circulation that affects the entire tropics. Furthermore, whereas previous studies suggest lower TC activity despite stronger summer insolation and warmer sea surface temperature in the Northern Hemisphere, accounting for the Sahara greening and reduced dust concentrations leads instead to an increase of TC activity in both hemispheres, particularly over the Caribbean basin and East Coast of North America. Our study highlights the importance of regional changes in land cover and dust concentrations in affecting the potential intensity and genesis of past TCs and suggests that both factors may have appreciable influence on TC activity in a future warmer climate.

BMP15 Mutations Associated With Primary Ovarian Insufficiency Reduce Expression, Activity, or Synergy With GDF9.

PubMed

Patiño, Liliana C; Walton, Kelly L; Mueller, Thomas D; Johnson, Katharine E; Stocker, William; Richani, Dulama; Agapiou, David; Gilchrist, Robert B; Laissue, Paul; Harrison, Craig A

2017-03-01

Bone morphogenetic protein (BMP)15 is an oocyte-specific growth factor, which, together with growth differentiation factor (GDF) 9, regulates folliculogenesis and ovulation rate. Multiple mutations in BMP15 have been identified in women with primary ovarian insufficiency (POI), supporting a pathogenic role; however, the underlying biological mechanism of many of these mutants remains unresolved. To determine how mutations associated with ovarian dysfunction alter the biological activity of human BMP15. The effects of 10 mutations in BMP15 on protein production, activation of granulosa cells, and synergy with GDF9 were assessed. Sequencing of 35 patients with POI identified both an unrecognized BMP15 variant (c.986G>A, R329H) and a variant (c.581T>C, F194S) previously associated with the condition. Assessing expression and activity of these and 8 other BMP15 mutants identified: (1) multiple variants, including L148P, F194S, and Y235C, with reduced mature protein production; (2) three variants (R138H, A180T, and R329H) with ∼fourfold lower activity than wild-type BMP15; and (3) 3 variants (R68W, F194S, and N196K) with a significantly reduced ability to synergize with GDF9. Mutations in BMP15 associated with POI reduce mature protein production, activity, or synergy with GDF9. The latter effect is perhaps most interesting given that interactions with GDF9 most likely underlie the physiology of BMP15 in the human ovary. Copyright © 2017 by the Endocrine Society

Gardening as a potential activity to reduce falls in older adults.

PubMed

Chen, Tuo-Yu; Janke, Megan C

2012-01-01

This study examines whether participation in gardening predicts reduced fall risk and performance on balance and gait-speed measures in older adults. Data on adults age 65 and older (N = 3,237) from the Health and Retirement Study and Consumption and Activities Mail Survey were analyzed. Participants who spent 1 hr or more gardening in the past week were defined as gardeners, resulting in a total of 1,585 gardeners and 1,652 nongardeners. Independent t tests, chi square, and regression analyses were conducted to examine the relationship between gardening and health outcomes. Findings indicate that gardeners reported significantly better balance and gait speed and had fewer chronic conditions and functional limitations than nongardeners. Significantly fewer gardeners than nongardeners reported a fall in the past 2 yr. The findings suggest that gardening may be a potential activity to incorporate into future fall-prevention programs.

Systematic review of the association between physical activity and burnout

PubMed Central

Naczenski, Lea M.; de Vries, Juriena D.; van Hooff, Madelon L. M.; Kompier, Michiel A. J.

2017-01-01

Objective: Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical activity and burnout by conducting a systematic review of longitudinal and intervention studies. Methods: A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). Results: In longitudinal studies, we found moderately strong evidence (SIC (4) = -1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC (6) = -0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. Conclusions: This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout. PMID:28993574

Systematic review of the association between physical activity and burnout.

PubMed

Naczenski, Lea M; Vries, Juriena D de; Hooff, Madelon L M van; Kompier, Michiel A J

2017-11-25

Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical activity and burnout by conducting a systematic review of longitudinal and intervention studies. A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). In longitudinal studies, we found moderately strong evidence (SIC (4) = -1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC (6) = -0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout.

A Midwinter Minimum in North Atlantic Storm Track Intensity in Years of a Strong Jet

NASA Astrophysics Data System (ADS)

Afargan, H.; Kaspi, Y.

2017-12-01

This study investigates the occurrence of a midwinter suppression in synoptic eddy activity within the North Atlantic storm track. It is found that eddy kinetic energy over the Atlantic is reduced during winter relative to fall and spring, despite the stronger wintertime jet and enhanced baroclinicity. This behavior is similar to the well-known Pacific midwinter minimum, yet the reduction over the Atlantic is smaller and persists for a shorter period. To examine the conditions favorable for this phenomenon, we present an analysis of years with stronger jet intensity versus years of weaker jets over the Atlantic and Pacific basins. When the wintertime jet is stronger, the midwinter suppression of eddy activity is more pronounced, and the jet is more equatorward. Since the climatological Atlantic jet is weaker relative to the Pacific jet, the conditions for a midwinter suppression in the Atlantic are generally less favorable, yet a midwinter suppression often occurs in years of a strong jet.

Will reducing sugar-sweetened beverage consumption reduce obesity? Evidence supporting conjecture is strong, but evidence when testing effect is weak

PubMed Central

Kaiser, Kathryn A.; Shikany, James M.; Keating, Karen D.; Allison, David B.

2014-01-01

We provide arguments to the debate question and update a previous meta-analysis with recently published studies on effects of sugar-sweetened beverages (SSBs) on body weight/composition indices (BWIs). We abstracted data from randomized controlled trials examining effects of consumption of SSBs on BWIs. Six new studies met these criteria: 1) human trials, 2) 3 weeks duration, 3) random assignment to conditions differing only in consumption of SSBs, and 4) including a BWI outcome. Updated meta-analysis of a total of seven studies that added SSBs to persons’ diets showed dose-dependent increases in weight. Updated meta-analysis of eight studies attempting to reduce SSB consumption showed an equivocal effect on BWIs in all randomized subjects. When limited to subjects overweight at baseline, meta-analysis showed a significant effect of roughly 0.25 standard deviations (more weight loss/less weight gain) relative to controls. Evidence to date is equivocal in showing that decreasing SSB consumption will reduce the prevalence of obesity. Although new evidence suggests that an effect may yet be demonstrable in some populations, the integrated effect size estimate remains very small and of equivocal statistical significance. Problems in this research area and suggestions for future research are highlighted. PMID:23742715

77 FR 53212 - Notice of Proposed Information Collection: Comment Request Strong Cities Strong Communities...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

... Information Collection: Comment Request Strong Cities Strong Communities National Resource Network AGENCY... National Resource Network. OMB Control Number, if applicable: 2528--Pending. Description of the need for... information related to the proposed Strong Cities Strong Communities National Resource Network. The U.S...

Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats.

PubMed

Shao, Yiye; Wang, Cuicui; Hong, Zhen; Chen, Yinghui

2016-03-01

It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up-regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase (MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug (AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38MAPK could participate in drug resistance in refractory epilepsy through the regulation of P-gp. We show that the specific inhibitor of p38MAPK could down-regulate the expression of multidrug transporter (P-glycoprotein) in blood-brain barrier, increase the concentration of antiepileptic drugs in the hippocampal extracellular fluid and reduce anti-epileptic drug resistance in refractory epileptic rats. We propose that the p38MAPK signaling pathway participates in drug resistance in refractory epilepsy through the regulation of P-glycoprotein expression. © 2015 International Society for Neurochemistry.

Developing Strong Geoscience Programs and Departments

NASA Astrophysics Data System (ADS)

MacDonald, R.; Manduca, C. A.

2002-12-01

Strong geoscience programs are essential for preparing future geoscientists and developing a broad public understanding of our science. Faculty working as a department team can create stronger programs than individual faculty working alone. Workshops sponsored by Project Kaleidoscope (www.pkal.org) on departmental planning in the geosciences have emphasized the importance of designing programs in the context of both departmental and student goals. Well-articulated goals form a foundation for designing curriculum, courses, and other departmental activities. Course/skill matrices have emerged as particularly valuable tools for analyzing how individual courses combine in a curriculum to meet learning goals. Integrated programs where students have opportunities to learn and use skills in multiple contexts have been developed at several institutions. Departments are leveraging synergies between courses to more effectively reach departmental goals and capitalize on opportunities in the larger campus environment. A full departmental program extends beyond courses and curriculum. Studies in physics (National Task Force on Undergraduate Physics, Hilborne, 2002) indicate the importance of activities such as recruiting able students, mentoring students, providing courses appropriate for pre-service K-12 teachers, assisting with professional development for a diversity of careers, providing opportunities for undergraduates to participate in research, and making connections with the local industries and businesses that employ graduates. PKAL workshop participants have articulated a wide variety of approaches to undergraduate research opportunities within and outside of class based on their departmental goals, faculty goals, and resources. Similarly, departments have a wide variety of strategies for developing productive synergies with campus-wide programs including those emphasizing writing skills, quantitative skills, and environmental studies. Mentoring and advising

Strong synergism of dexamethasone in combination with fluconazole against resistant Candida albicans mediated by inhibiting drug efflux and reducing virulence.

PubMed

Sun, Wenwen; Wang, Decai; Yu, Cuixiang; Huang, Xin; Li, Xiuyun; Sun, Shujuan

2017-09-01

Candida albicans is the most commonly isolated Candida spp. in the clinic and its resistance to fluconazole (FLC) has been emerging rapidly. Combination therapy may be a potentially effective approach to combat drug resistance. In this study, the combination antifungal effects of dexamethasone (DXM) and FLC against resistant C. albicans in vitro were assayed using minimum inhibitory concentrations (MICs), sessile MICs and time-kill curves. The in vivo efficacy of this drug combination was evaluated using a Galleria mellonella model by determining survival rate, fungal burden and histological damage. In addition, the impact of DXM on efflux pump activity was investigated using a rhodamine 6G assay. Expression of CDR1, CDR2 and MDR1 was determined by real-time quantitative PCR, and extracellular phospholipase activity was detected by the egg yolk agar method to reveal the potential synergistic mechanism. The results showed that DXM potentiates the antifungal effect of FLC against resistant C. albicans strains both in vitro and in vivo, and the synergistic mechanism is related to inhibiting the efflux of drugs and reducing the virulence of C. albicans. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Swimming Motility Reduces Deposition to Silica Surfaces

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

Lu, Nanxi; Massoudieh, Arash; Liang, Xiaomeng

The role of swimming motility on bacterial transport and fate in porous media was evaluated. We present microscopic evidence showing that strong swimming motility reduces attachment of Azotobacter vinelandii cells to silica surfaces. Applying global and cluster statistical analyses to microscopic videos taken under non-flow conditions, wild type, flagellated A. vinelandii strain DJ showed strong swimming ability with an average speed of 13.1 μm/s, DJ77 showed impaired swimming averaged at 8.7 μm/s, and both the non-flagellated JZ52 and chemically treated DJ cells were non-motile. Quantitative analyses of trajectories observed at different distances above the collector of a radial stagnation pointmore » flow cell (RSPF) revealed that both swimming and non-swimming cells moved with the flow when at a distance of at least 20 μm from the collector surface. Near the surface, DJ cells showed both horizontal and vertical movement diverging them from reaching surfaces, while chemically treated DJ cells moved with the flow to reach surfaces, suggesting that strong swimming reduced attachment. In agreement with the RSPF results, the deposition rates obtained for two-dimensional multiple-collector micromodels were also lowest for DJ, while DJ77 and JZ52 showed similar values. Strong swimming specifically reduced deposition on the upstream surfaces of the micromodel collectors.« less

Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

PubMed

Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

2013-02-01

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

Spaced sessions of avoidance extinction reduce spontaneous recovery and promote infralimbic cortex activation.

PubMed

Tapias-Espinosa, Carles; Kádár, Elisabet; Segura-Torres, Pilar

2018-01-15

Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA). We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex. The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner.

PubMed

Eichhorn, Tanja; Rauscher, Sabine; Hammer, Caroline; Gröger, Marion; Fischer, Michael B; Weber, Viktoria

2016-10-01

Endothelial activation with excessive recruitment and adhesion of immune cells plays a central role in the progression of sepsis. We established a microfluidic system to study the activation of human umbilical vein endothelial cells by conditioned medium containing plasma from lipopolysaccharide-stimulated whole blood or from septic blood and to investigate the effect of adsorption of inflammatory mediators on endothelial activation. Treatment of stimulated whole blood with polystyrene-divinylbenzene-based cytokine adsorbents (average pore sizes 15 or 30 nm) prior to passage over the endothelial layer resulted in significantly reduced endothelial cytokine and chemokine release, plasminogen activator inhibitor-1 secretion, adhesion molecule expression, and in diminished monocyte adhesion. Plasma samples from sepsis patients differed substantially in their potential to induce endothelial activation and monocyte adhesion despite their almost identical interleukin-6 and tumor necrosis factor-alpha levels. Pre-incubation of the plasma samples with a polystyrene-divinylbenzene-based adsorbent (30 nm average pore size) reduced endothelial intercellular adhesion molecule-1 expression to baseline levels, resulting in significantly diminished monocyte adhesion. Our data support the potential of porous polystyrene-divinylbenzene-based adsorbents to reduce endothelial activation under septic conditions by depletion of a broad range of inflammatory mediators.

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption

PubMed Central

Smith-Anttila, Casey J.A.; Nordenankar, Karin; Arvidsson, Emma; Mahmoudi, Souha; Zampera, André; Wärner Jonsson, Hanna; Bergquist, Jonas; Lévesque, Daniel; Andersson, Malin; Dumas, Sylvie

2016-01-01

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson’s disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system. PMID:27699212

Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption.

PubMed

Schweizer, Nadine; Viereckel, Thomas; Smith-Anttila, Casey J A; Nordenankar, Karin; Arvidsson, Emma; Mahmoudi, Souha; Zampera, André; Wärner Jonsson, Hanna; Bergquist, Jonas; Lévesque, Daniel; Konradsson-Geuken, Åsa; Andersson, Malin; Dumas, Sylvie; Wallén-Mackenzie, Åsa

2016-01-01

The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson's disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene ( Vglut2/Slc17a6 ) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.

Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity.

PubMed

Romero, José R; Suzuka, Sandra M; Nagel, Ronald L; Fabry, Mary E

2002-02-15

Nitric oxide (NO), essential for maintaining vascular tone, is produced from arginine by nitric oxide synthase. Plasma arginine levels are low in sickle cell anemia, and it is reported here that low plasma arginine is also found in our sickle transgenic mouse model that expresses human alpha, human beta(S), and human beta(S-Antilles) and is homozygous for the mouse beta(major) deletion (S+S-Antilles). S+S-Antilles mice were supplemented with a 4-fold increase in arginine that was maintained for several months. Mean corpuscular hemoglobin concentration (MCHC) decreased and the percent high-density red cells was reduced. Deoxy K(+) efflux is characteristic of red cells in sickle cell disease and contributes to the disease process by increasing the MCHC and rendering the cells more susceptible to polymer formation. This flux versus the room air flux was reduced in S+S-Antilles red cells from an average value of 1.6 +/- 0.3 mmol per liter of red cells x minute (FU) in nonsupplemented mice to 0.9 +/- 0.3 FU (n = 4, P < .02, paired t test) in supplemented mice. In room air, V(max) of the Ca(++)-activated K(+) channel (Gardos) was reduced from 4.1 +/- 0.6 FU (off diet) to 2.6 +/- 0.4 FU (n = 7 and 8, P < .04, t test) in arginine-supplemented mice versus clotrimazole. In conclusion, the major mechanism by which arginine supplementation reduces red cell density (MCHC) in S+S-Antilles mice is by inhibiting the Ca(++)-activated K(+) channel.

Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli.

PubMed

Ki, Jason J; Kelly, Simon P; Parra, Lucas C

2016-03-09

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we "absorb" that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative. Copyright © 2016 Ki et al.

Effects of reduced carbonic anhydrase activity on CO2 assimilation rates in Setaria viridis: a transgenic analysis.

PubMed

Osborn, Hannah L; Alonso-Cantabrana, Hugo; Sharwood, Robert E; Covshoff, Sarah; Evans, John R; Furbank, Robert T; von Caemmerer, Susanne

2017-01-01

In C 4 species, the major β-carbonic anhydrase (β-CA) localized in the mesophyll cytosol catalyses the hydration of CO 2 to HCO 3 - , which phosphoenolpyruvate carboxylase uses in the first step of C 4 photosynthesis. To address the role of CA in C 4 photosynthesis, we generated transgenic Setaria viridis depleted in β-CA. Independent lines were identified with as little as 13% of wild-type CA. No photosynthetic defect was observed in the transformed lines at ambient CO 2 partial pressure (pCO 2 ). At low pCO 2 , a strong correlation between CO 2 assimilation rates and CA hydration rates was observed. C 18 O 16 O isotope discrimination was used to estimate the mesophyll conductance to CO 2 diffusion from the intercellular air space to the mesophyll cytosol (g m ) in control plants, which allowed us to calculate CA activities in the mesophyll cytosol (C m ). This revealed a strong relationship between the initial slope of the response of the CO 2 assimilation rate to cytosolic pCO 2 (AC m ) and cytosolic CA activity. However, the relationship between the initial slope of the response of CO 2 assimilation to intercellular pCO 2 (AC i ) and cytosolic CA activity was curvilinear. This indicated that in S. viridis, mesophyll conductance may be a contributing limiting factor alongside CA activity to CO 2 assimilation rates at low pCO 2 . © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Hydrocarbon activation under sulfate-reducing and methanogenic conditions proceeds by different mechanisms.

NASA Astrophysics Data System (ADS)

Head, Ian; Gray, Neil; Aitken, Caroline; Sherry, Angela; Jones, Martin; Larter, Stephen

2010-05-01

Microbial degradation of alkanes typically involves their conversion to fatty acids which are then catabolised by beta-oxidation. The critical step in this process is activation of the hydrocarbon. Under oxic conditions this is catalyzed by monooxygenase enzymes with the formation of long chain alcohols. In the absence of oxygen alternative alkane activation mechanisms have been observed or proposed. Fumarate addition to alkanes to form alkyl succinates is considered a central process in anaerobic hydrocarbon degradation. Comparative studies of crude oil degradation under sulphate-reducing and methanogenic conditions revealed distinctive patterns of compound class removal and metabolite formation. Alkyl succinates derived from C7 to C26 n-alkanes and branched chain alkanes were found in abundance in sulfate-reducing systems but these were not detected during methanogenic crude oil degradation. Only one other mechanism of alkane activation has been elucidated to date. This involves addition of carbon derived from bicarbonate/CO2 to C-3 of an alkane chain to form a 2-ethylalkane with subsequent removal of the ethyl group leading to the formation of a fatty acid 1 carbon shorter than the original alkane. 2-ethylalkanes have never been detected as metabolites of anaerobic alkane degradation and were not detected in crude oil-degrading methanogenic systems. Due to the range of alkanes present in crude oil it was not possible to infer the generation of C-odd acids from C-even alkanes which is characteristic of the C-3 carboxylation mechanism. Furthermore genes homologous to alkysuccinate synthetases were not detected in the methanogenic hydrocarbon degrading community by pyrosequencing of total DNA extracted from methanogenic enrichments cultures. beta-oxidation genes were detected and intriguingly, alcohol and aldehyde dehydrogenase genes were present. This offers the possibility that alkane activation in the methanogenic system does not proceed via acid metabolites

Lingering effects of preceding strong El Niño events on the typhoon activity in early summer: Case study of sub-seasonal and seasonal predictions in 2016

NASA Astrophysics Data System (ADS)

Takaya, Y.; Kubo, Y.; Yamaguchi, M.; Vitart, F.; Hirahara, S.; Maeda, S.

2016-12-01

Strong El Niño events have lingering effects on the seasonal variability in the Indo- western Pacific region in the mature-decay phase of El Niño. Specifically, in the decay phase, a low-level anticyclonic circulation and suppressed convection in the western North Pacific are enforced as a result of a local air-sea feedback in the western North Pacific and remote response to the Indian Ocean warming due to El Niño. The typhoon activity in the western North Pacific is also modulated by the lingering effects in the early typhoon season (boreal spring to early summer) following the strong El Niño events. This study investigates underlying mechanisms and predictability by analyzing the historical analysis data, subseasonal and seasonal reforecast data, and sensitivity experiments with the use of an atmosphere-ocean coupled model for the 2016 typhoon season. In this study, we focus on the remote response of the typhoon activity in the Indo-Pacific region. First, we examined the case of 2016, which exhibited the striking inactive typhoon activity and marked the second latest genesis of the first typhoon of the year since 1977 (Typhoon Nipartak on 3 July 2016). The inactive typhoon activity in the early typhoon season of 2016 is plausibly related to the lingering effects of the preceding strong El Niño in 2015/2016 winter. And the inactive typhoon condition and its related atmosphere-ocean conditions in the western north Pacific were successfully predicted with sub-seasonal prediction systems and JMA seasonal prediction system (JMA/MRI-CPS2) well in advance. A composite analysis using historical analysis data indicates that the typhoon activity tends to be suppressed associated with the Indian Ocean warming in boreal spring to summer following El Niño winters. This is relatively well replicated in reforecasts of JMA/MRI-CPS2. We also carried out sensitivity experiments with JMA/MRI-CPS2, where we strongly nudge sea surface temperature (SST) in the Indian Ocean to

Subjective Word-Finding Difficulty Reduces Engagement in Social Leisure Activities in Alzheimer’s Disease

PubMed Central

Farrell, Meagan T.; Zahodne, Laura B.; Stern, Yaakov; Dorrejo, Jhedy; Yeung, Philip; Cosentino, Stephanie

2014-01-01

Objectives To assess the influence of subjective word-finding difficulty on Alzheimer’s disease (AD) patients’ likelihood of engaging in social leisure activities. Design Analysis of data collected from the second cohort of the Multicenter Study of Predictors of Disease Course in Alzheimer’s disease. Setting Four study sites in the U.S. and France. Participants Individuals diagnosed with mild to moderate AD (N = 236) Measurements On separate questionnaires, patients were asked to 1) report whether had trouble finding the right word when speaking (subjective word-finding difficulty), and 2) rate their frequency and enjoyment of both social and nonsocial leisure activities. Objective language measures included object naming and verbal fluency. Measures of dependence, depression, cognitive status, age, sex, and education were also included as covariates in regression analyses. Results Over half (52%) of the sample reported word-finding difficulty, and subjective complaints were correlated with poorer verbal fluency scores. Subjective word-finding difficulty was uniquely related to social activity measures. Endorsers of word-finding difficulty reported reduced frequency and enjoyment of social leisure activities, controlling for covariates. In contrast, engagement in nonsocial activities was associated with higher age and depression scores, but was not related to word-finding complaints. These results were corroborated by the caregivers’ reports, and occurred above and beyond the effect of objective word-finding ability. Conclusion AD patients who are aware of increasing word-finding failures are less likely to participate in and enjoy socially-oriented leisure activities. This finding may have significant implications for clinical and health outcomes in AD. A failure to evaluate subjective language complaints could result in social withdrawal symptoms, thereby threatening the patient’s quality of life as well as increasing caregiver burden. Importantly

Process for reducing beta activity in uranium

DOEpatents

Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

1986-10-07

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

Process for reducing beta activity in uranium

DOEpatents

Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

1986-01-01

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

Process for reducing beta activity in uranium

DOEpatents

Briggs, G.G.; Kato, T.R.; Schonegg, E.

1985-04-11

This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

2017-09-01

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

Flow and active mixing have a strong impact on bacterial growth dynamics in the proximal large intestine

NASA Astrophysics Data System (ADS)

Cremer, Jonas; Segota, Igor; Yang, Chih-Yu; Arnoldini, Markus; Groisman, Alex; Hwa, Terence

2016-11-01

More than half of fecal dry weight is bacterial mass with bacterial densities reaching up to 1012 cells per gram. Mostly, these bacteria grow in the proximal large intestine where lateral flow along the intestine is strong: flow can in principal lead to a washout of bacteria from the proximal large intestine. Active mixing by contractions of the intestinal wall together with bacterial growth might counteract such a washout and allow high bacterial densities to occur. As a step towards understanding bacterial growth in the presence of mixing and flow, we constructed an in-vitro setup where controlled wall-deformations of a channel emulate contractions. We investigate growth along the channel under a steady nutrient inflow. Depending on mixing and flow, we observe varying spatial gradients in bacterial density along the channel. Active mixing by deformations of the channel wall is shown to be crucial in maintaining a steady-state bacterial population in the presence of flow. The growth-dynamics is quantitatively captured by a simple mathematical model, with the effect of mixing described by an effective diffusion term. Based on this model, we discuss bacterial growth dynamics in the human large intestine using flow- and mixing-behavior having been observed for humans.

O-GlcNAc modification of PPAR{gamma} reduces its transcriptional activity

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

Ji, Suena; Park, Sang Yoon; Roth, Juergen

2012-01-27

Highlights: Black-Right-Pointing-Pointer We found that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The Thr54 of PPAR{gamma}1 is the major O-GlcNAc site. Black-Right-Pointing-Pointer Transcriptional activity of PPAR{gamma}1 was decreased on treatment with the OGA inhibitor. -- Abstract: The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The {beta}-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1more » adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPAR{gamma} is the major O-GlcNAc site. Transcriptional activity of wild type PPAR{gamma} was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPAR{gamma} did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPAR{gamma} transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPAR{gamma} influences its transcriptional activity and is involved in adipocyte differentiation.« less

Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.

PubMed

Shen, Jia; Bai, Xiao-Yin; Qin, Yuan; Jin, Wei-Wei; Zhou, Jing-Yin; Zhou, Ji-Ping; Yan, Ying-Gang; Wang, Qiong; Bruce, Iain C; Chen, Jiang-Hua; Xia, Qiang

2011-06-15

Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP. Copyright © 2011 Elsevier Inc. All rights reserved.

Tropical cyclone activity enhanced by Sahara greening and reduced dust emissions during the African Humid Period

PubMed Central

Pausata, Francesco S. R.; Emanuel, Kerry A.; Chiacchio, Marc; Diro, Gulilat T.; Zhang, Qiong; Sushama, Laxmi; Stager, J. Curt; Donnelly, Jeffrey P.

2017-01-01

Tropical cyclones (TCs) can have devastating socioeconomic impacts. Understanding the nature and causes of their variability is of paramount importance for society. However, historical records of TCs are too short to fully characterize such changes and paleo-sediment archives of Holocene TC activity are temporally and geographically sparse. Thus, it is of interest to apply physical modeling to understanding TC variability under different climate conditions. Here we investigate global TC activity during a warm climate state (mid-Holocene, 6,000 yBP) characterized by increased boreal summer insolation, a vegetated Sahara, and reduced dust emissions. We analyze a set of sensitivity experiments in which not only solar insolation changes are varied but also vegetation and dust concentrations. Our results show that the greening of the Sahara and reduced dust loadings lead to more favorable conditions for tropical cyclone development compared with the orbital forcing alone. In particular, the strengthening of the West African Monsoon induced by the Sahara greening triggers a change in atmospheric circulation that affects the entire tropics. Furthermore, whereas previous studies suggest lower TC activity despite stronger summer insolation and warmer sea surface temperature in the Northern Hemisphere, accounting for the Sahara greening and reduced dust concentrations leads instead to an increase of TC activity in both hemispheres, particularly over the Caribbean basin and East Coast of North America. Our study highlights the importance of regional changes in land cover and dust concentrations in affecting the potential intensity and genesis of past TCs and suggests that both factors may have appreciable influence on TC activity in a future warmer climate. PMID:28559352

Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge.

PubMed

Liu, Mei; Gill, Jason J; Young, Ry; Summer, Elizabeth J

2015-09-09

Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages--GordTnk2, Gmala1, and GordDuk1--had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5-15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment.

Tailored activities to manage neuropsychiatric behaviors in persons with dementia and reduce caregiver burden: a randomized pilot study.

PubMed

Gitlin, Laura N; Winter, Laraine; Burke, Janice; Chernett, Nancy; Dennis, Marie P; Hauck, Walter W

2008-03-01

To test whether the Tailored Activity Program (TAP) reduces dementia-related neuropsychiatric behaviors, promotes activity engagement, and enhances caregiver well-being. Prospective, two-group (treatment, wait-list control), randomized, controlled pilot study with 4 months as main trial endpoint. At 4 months, controls received the TAP intervention and were reassessed 4 months later. Patients' homes. Sixty dementia patients and family caregivers. The eight-session occupational therapy intervention involved neuropsychological and functional testing, selection, and customization of activities to match capabilities identified in testing, and instruction to caregivers in use of activities. Behavioral occurrences, activity engagement, and quality of life in dementia patients; objective and subjective burden and skill enhancement in caregivers. At 4 months, compared with controls, intervention caregivers reported reduced frequency of problem behaviors, and specifically for shadowing and repetitive questioning, and greater activity engagement including the ability to keep busy. Fewer intervention caregivers reported agitation or argumentation. Caregiver benefits included fewer hours doing things and being on duty, greater mastery, self-efficacy, and skill enhancement. Wait-list control participants following intervention showed similar benefits for reductions in behavioral frequency and caregiver hours doing things for the patient and mastery. Caregivers with depressed symptoms derived treatment benefits similar to nondepressed caregivers. Tailoring activities to the capabilities of dementia patients and training families in activity use resulted in clinically relevant benefits for patients and caregivers. Treatment minimized trigger behaviors for nursing home placement and reduced objective caregiver burden. Noteworthy is that depressed caregivers effectively engaged in and benefited from the intervention.

Activity-based anorexia is associated with reduced hippocampal cell proliferation in adolescent female rats.

PubMed

Barbarich-Marsteller, Nicole C; Fornal, Casimir A; Takase, Luiz F; Bocarsly, Miriam E; Arner, Candice; Walsh, B Timothy; Hoebel, Bartley G; Jacobs, Barry L

2013-01-01

Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics core features of the clinical psychiatric disorder, including severe food restriction, weight loss, and hyperactivity. The ABA model is currently being used to study starvation-induced changes in the brain. Here, we examined hippocampal cell proliferation in animals with ABA (or the appropriate control conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups: control (24h/day food access), food-restricted (1h/day food access), exercise (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was injected and the rats were perfused 2h later. Brains were removed and subsequently processed for BrdU and Ki67 immunohistochemistry. The acute induction of ABA reduced cell proliferation in the dentate gyrus. This effect was significant in the hilus region of the dentate gyrus, but not in the subgranular zone, where adult neurogenesis occurs. Marked decreases in cell proliferation were also observed in the surrounding dorsal hippocampus and in the corpus callosum. These results indicate a primary effect on gliogenesis rather than neurogenesis following 3 days of ABA. For each brain region studied (except SGZ), there was a strong positive correlation between the level of cell proliferation and body weight/food intake. Future studies should examine whether these changes are maintained following long-term weight restoration and whether alterations in neurogenesis occur following longer exposures to ABA. Copyright © 2012 Elsevier B.V. All rights reserved.

Thermally Reduced Graphene Oxide Electrochemically Activated by Bis-Spiro Quaternary Alkyl Ammonium for Capacitors.

PubMed

He, Tieshi; Meng, Xiangling; Nie, Junping; Tong, Yujin; Cai, Kedi

2016-06-08

Thermally reduced graphene oxide (RGO) electrochemically activated by a quaternary alkyl ammonium-based organic electrolytes/activated carbon (AC) electrode asymmetric capacitor is proposed. The electrochemical activation process includes adsorption of anions into the pores of AC in the positive electrode and the interlayer intercalation of cations into RGO in the negative electrode under high potential (4.0 V). The EA process of RGO by quaternary alkyl ammonium was investigated by X-ray diffraction and electrochemical measurements, and the effects of cation size and structure were extensively evaluated. Intercalation by quaternary alkyl ammonium demonstrates a small degree of expansion of the whole crystal lattice (d002) and a large degree of expansion of the partial crystal lattice (d002) of RGO. RGO electrochemically activated by bis-spiro quaternary alkyl ammonium in propylene carbonate/AC asymmetric capacitor exhibits good activated efficiency, high specific capacity, and stable cyclability.

Reduced posterior parietal cortex activation after training on a visual search task.

PubMed

Bueichekú, Elisenda; Miró-Padilla, Anna; Palomar-García, María-Ángeles; Ventura-Campos, Noelia; Parcet, María-Antonia; Barrós-Loscertales, Alfonso; Ávila, César

2016-07-15

Gaining experience on a cognitive task improves behavioral performance and is thought to enhance brain efficiency. Despite the body of literature already published on the effects of training on brain activation, less research has been carried out on visual search attention processes under well controlled conditions. Thirty-six healthy adults divided into trained and control groups completed a pre-post letter-based visual search task fMRI study in one day. Twelve letters were used as targets and ten as distractors. The trained group completed a training session (840 trials) with half the targets between scans. The effects of training were studied at the behavioral and brain levels by controlling for repetition effects using both between-subjects (trained vs. control groups) and within-subject (trained vs. untrained targets) controls. The trained participants reduced their response speed by 31% as a result of training, maintaining their accuracy scores, whereas the control group hardly changed. Neural results revealed that brain changes associated with visual search training were circumscribed to reduced activation in the posterior parietal cortex (PPC) when controlling for group, and they included inferior occipital areas when controlling for targets. The observed behavioral and brain changes are discussed in relation to automatic behavior development. The observed training-related decreases could be associated with increased neural efficiency in specific key regions for task performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural Determinants of Sleeping Beauty Transposase Activity

PubMed Central

Abrusán, György; Yant, Stephen R; Szilágyi, András; Marsh, Joseph A; Mátés, Lajos; Izsvák, Zsuzsanna; Barabás, Orsolya; Ivics, Zoltán

2016-01-01

Transposases are important tools in genome engineering, and there is considerable interest in engineering more efficient ones. Here, we seek to understand the factors determining their activity using the Sleeping Beauty transposase. Recent work suggests that protein coevolutionary information can be used to classify groups of physically connected, coevolving residues into elements called “sectors”, which have proven useful for understanding the folding, allosteric interactions, and enzymatic activity of proteins. Using extensive mutagenesis data, protein modeling and analysis of folding energies, we show that (i) The Sleeping Beauty transposase contains two sectors, which span across conserved domains, and are enriched in DNA-binding residues, indicating that the DNA binding and endonuclease functions of the transposase coevolve; (ii) Sector residues are highly sensitive to mutations, and most mutations of these residues strongly reduce transposition rate; (iii) Mutations with a strong effect on free energy of folding in the DDE domain of the transposase significantly reduce transposition rate. (iv) Mutations that influence DNA and protein-protein interactions generally reduce transposition rate, although most hyperactive mutants are also located on the protein surface, including residues with protein-protein interactions. This suggests that hyperactivity results from the modification of protein interactions, rather than the stabilization of protein fold. PMID:27401040

Calibrating First-Order Strong Lensing Mass Estimates in Clusters of Galaxies

NASA Astrophysics Data System (ADS)

Reed, Brendan; Remolian, Juan; Sharon, Keren; Li, Nan; SPT Clusters Cooperation

2018-01-01

We investigate methods to reduce the statistical and systematic errors inherent to using the Einstein Radius as a first-order mass estimate in strong lensing galaxy clusters. By finding an empirical universal calibration function, we aim to enable a first-order mass estimate of large cluster data sets in a fraction of the time and effort of full-scale strong lensing mass modeling. We use 74 simulated cluster data from the Argonne National Laboratory in a lens redshift slice of [0.159, 0.667] with various source redshifts in the range of [1.23, 2.69]. From the simulated density maps, we calculate the exact mass enclosed within the Einstein Radius. We find that the mass inferred from the Einstein Radius alone produces an error width of ~39% with respect to the true mass. We explore an array of polynomial and exponential correction functions with dependence on cluster redshift and projected radii of the lensed images, aiming to reduce the statistical and systematic uncertainty. We find that the error on the the mass inferred from the Einstein Radius can be reduced significantly by using a universal correction function. Our study has implications for current and future large galaxy cluster surveys aiming to measure cluster mass, and the mass-concentration relation.

Amygdala Lesions Reduce Cataplexy in Orexin KO mice

PubMed Central

Burgess, C.R.; Oishi, Y.; Mochizuki, T.; Peever, J.H.; Scammell, T.E.

2013-01-01

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of REM sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal grey, lateral pontine tegmentum, locus coeruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knockout mice, a model of narcolepsy. These lesions did not alter basic sleep/wake behavior, but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia. PMID:23739970

A DPYD variant (Y186C) in individuals of African ancestry associated with reduced DPD enzyme activity

PubMed Central

Offer, Steven M.; Lee, Adam M.; Mattison, Lori K.; Fossum, Croix; Wegner, Natalie J.; Diasio, Robert B.

2013-01-01

5-fluorouracil (5-FU) is used to treat many aggressive cancers, such as those of the colon, breast, and head & neck. The responses to 5-FU, both toxicity and efficacy, vary between racial groups, potentially due to variability in enzyme activity of dihydropyrimidine dehydrogenase (DPD, encoded by DPYD). In the present study, the genetic associations between DPYD variations and circulating mononuclear cell DPD enzyme activity were evaluated in 94 African American and 81 European American volunteers. The DPYD-Y186C variant was unique to individuals of African ancestry, and DPD activity was 46% reduced in carriers compared to non-carriers (279±35 compared to 514±168 pmol 5-FU min−1 mg−1; P=0.00029). 26% of the African Americans with reduced DPD activity in this study carried Y186C. In the African American cohort, following exclusion of Y186C carriers, homozygous carriers of C29R showed 27% higher DPD activity compared to non-carriers (609±152 and 480±152 pmol 5-FU min−1 mg−1, respectively; P=0.013). PMID:23588312

A transgenic apple callus showing reduced polyphenol oxidase activity and lower browning potential.

PubMed

Murata, M; Nishimura, M; Murai, N; Haruta, M; Homma, S; Itoh, Y

2001-02-01

Polyphenol oxidase (PPO) is responsible for enzymatic browning of apples. Apples lacking PPO activity might be useful not only for the food industry but also for studies of the metabolism of polyphenols and the function of PPO. Transgenic apple calli were prepared by using Agrobacterium tumefaciens carrying the kanamycin (KM) resistant gene and antisense PPO gene. Four KM-resistant callus lines were obtained from 356 leaf explants. Among these transgenic calli, three calli grew on the medium containing KM at the same rate as non-transgenic callus on the medium without KM. One callus line had an antisense PPO gene, in which the amount and activity of PPO were reduced to half the amount and activity in non-transgenic callus. The browning potential of this line, which was estimated by adding chlorogenic acid, was also half the browning potential of non-transgenic callus.

Pomegranate ellagitannins inhibit α-glucosidase activity in vitro and reduce starch digestibility under simulated gastro-intestinal conditions.

PubMed

Bellesia, Andrea; Verzelloni, Elena; Tagliazucchi, Davide

2015-02-01

Pomegranate extract was tested for its ability to inhibit α-amylase and α-glucosidase activity. Pomegranate extract strongly inhibited rat intestinal α-glucosidase in vitro whereas it was a weak inhibitor of porcine α-amylase. The inhibitory activity was recovered in an ellagitannins-enriched fraction and punicalagin, punicalin, and ellagic acid were identified as α-glucosidase inhibitors (IC(50) of 140.2, 191.4, and 380.9 μmol/L, respectively). Kinetic analysis suggested that the pomegranate extract and ellagitannins inhibited α-glucosidase activity in a mixed mode. The inhibitory activity was demonstrated using an in vitro digestion system, mimicking the physiological gastro-intestinal condition, and potatoes as food rich in starch. Pre-incubation between ellagitannins and α-glucosidase increased the inhibitory activity, suggesting that they acted by binding to α-glucosidase. During digestion punicalin and punicalagin concentration decreased. Despite this loss, the pomegranate extract retained high inhibitory activity. This study suggests that pomegranate ellagitannins may inhibit α-glucosidase activity in vitro possibly affecting in vivo starch digestion.

Active galaxies. A strong magnetic field in the jet base of a supermassive black hole.

PubMed

Martí-Vidal, Ivan; Muller, Sébastien; Vlemmings, Wouter; Horellou, Cathy; Aalto, Susanne

2015-04-17

Active galactic nuclei (AGN) host some of the most energetic phenomena in the universe. AGN are thought to be powered by accretion of matter onto a rotating disk that surrounds a supermassive black hole. Jet streams can be boosted in energy near the event horizon of the black hole and then flow outward along the rotation axis of the disk. The mechanism that forms such a jet and guides it over scales from a few light-days up to millions of light-years remains uncertain, but magnetic fields are thought to play a critical role. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we have detected a polarization signal (Faraday rotation) related to the strong magnetic field at the jet base of a distant AGN, PKS 1830-211. The amount of Faraday rotation (rotation measure) is proportional to the integral of the magnetic field strength along the line of sight times the density of electrons. The high rotation measures derived suggest magnetic fields of at least tens of Gauss (and possibly considerably higher) on scales of the order of light-days (0.01 parsec) from the black hole. Copyright © 2015, American Association for the Advancement of Science.

Parasympathetic activation is involved in reducing epileptiform discharges when listening to Mozart music.

PubMed

Lin, Lung-Chang; Chiang, Ching-Tai; Lee, Mei-Wen; Mok, Hin-Kiu; Yang, Yi-Hsin; Wu, Hui-Chuan; Tsai, Chin-Lin; Yang, Rei-Cheng

2013-08-01

Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect. Our previous work revealed the positive effects of Mozart K.448 in reducing epileptiform discharges in children with epilepsy. However, the mechanism remains unclear. parasympathetic activation has been shown to help seizure control in many studies. In this study, we investigated the effect of Mozart music on epileptiform discharges and autonomic activity. Sixty-four epileptic children with epileptiform discharges were included. They all received electroencephalogram and electrocardiogram examinations simultaneously before, during, and after listening to Mozart K.448 or K.545. The total number of epileptiform discharges during each session (before, during, and after music) were divided by the duration (in minutes) of the session and then compared. Heart rate variability including time and frequency domain analysis was used to represent the autonomic function. The results showed that epileptiform discharges were significantly reduced during and right after listening to Mozart music (33.3 ± 31.1% reduction, p<0.001, during Mozart K.448 and 38.6 ± 43.3% reduction, p<0.001, during Mozart K.545) (28.1 ± 43.2% reduction, p<0.001, after Mozart K.448 and 46.0 ± 40.5% reduction, p<0.001, after Mozart K.545). No significant difference was noticed between the two pieces of music. The reduction was greatest in patients with generalized seizures and discharges. Significant increases in high-frequency (HF), the square root of the mean squared differences of successive RR intervals (RMSSD), the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute (bpm) were found during listening to Mozart music. Most of the patients with reduced epileptiform discharges also showed a decreased LF/HF ratio, low-frequency normalized units (LF nu), mean bpm, and an increased high-frequency normalized units (HF nu

Strong Navajo Marriages

ERIC Educational Resources Information Center

Skogrand, Linda; Mueller, Mary Lou; Arrington, Rachel; LeBlanc, Heidi; Spotted Elk, Davina; Dayzie, Irene; Rosenbrand, Reva

2008-01-01

The purpose of this qualitative study, conducted in two Navajo Nation chapters, was to learn what makes Navajo marriages strong because no research has been done on this topic. Twenty-one Navajo couples (42 individuals) who felt they had strong marriages volunteered to participate in the study. Couples identified the following marital strengths:…

Tritium retention in reduced-activation ferritic/martensitic steels

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

Hatano, Y.; Abe, S.; Matsuyama, M.

Reduced-activation ferritic/martensitic (RAFM) steels are structural material candidates for breeding blankets of future fusion reactors. Therefore, tritium (T) retention in RAFM steels is an important problem in assessing the T inventory of blankets. In this study, specimens of RAFM steels were subjected to irradiation of 20 MeV W ions to 0.54 displacements per atom (dpa), exposure to high flux D plasmas at 400 and 600 K and that to pulsed heat loads. The specimens thus prepared were exposed to DT gas at 473 K. Despite severe modification in the surface morphology, heat loads had negligible effects on T retention. Significantmore » increase in T retention at the surface and/or subsurface was observed after D plasma exposure. However, T trapped at the surface/subsurface layer was easily removed by maintaining the specimens in the air at about 300 K. Displacement damage led to increase in T retention in the bulk due to the trapping effects of defects, and T trapped was stable at 300 K. It was therefore concluded that displacement damages had the largest influence on T retention under the present conditions.« less

Effects of alloying elements and heat treatments on mechanical properties of Korean reduced-activation ferritic-martensitic steel

NASA Astrophysics Data System (ADS)

Chun, Y. B.; Kang, S. H.; Noh, S.; Kim, T. K.; Lee, D. W.; Cho, S.; Jeong, Y. H.

2014-12-01

As part of an alloy development program for Korean reduced-activation ferritic-martensitic (RAFM) steel, a total of 37 program alloys were designed and their mechanical properties were evaluated with special attention being paid to the effects of alloying elements and heat treatments. A reduction of the normalizing temperature from 1050 °C to 980 °C was found to have a positive effect on the impact resistance, resulting in a decrease in ductile-brittle transition-temperature (DBTT) of the program alloys by an average of 30 °C. The yield strength and creep rupture time are affected strongly by the tempering time at 760 °C but at the expense of ductility. Regarding the effects of the alloying elements, the addition of trace amounts of Zr enhances both the creep and impact resistance: the lowest DBTT was observed for the alloys containing 0.005 wt.% Zr, whereas the addition of 0.01 wt.% Zr extends the creep rupture-time under an accelerated condition. The enhanced impact resistance owing to the normalizing at lower temperature is attributed to a more refined grain structure, which provides more barriers to the propagation of cleavage cracks. Solution softening by Zr addition is suggested as a possible mechanism for enhanced resistance to both impact and creep of the program alloys.

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

PubMed

Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A; Cardozo, Christopher P

2011-10-14

Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy. Copyright © 2011. Published by Elsevier Inc.

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus

PubMed Central

The, FO; Cailotto, C; van der Vliet, J; de Jonge, WJ; Bennink, RJ; Buijs, RM; Boeckxstaens, GE

2011-01-01

BACKGROUND AND PURPOSE Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. EXPERIMENTAL APPROACH Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg−1) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. KEY RESULTS Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. CONCLUSIONS AND IMPLICATIONS Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. PMID:21371006

Mobile Phone Chips Reduce Increases in EEG Brain Activity Induced by Mobile Phone-Emitted Electromagnetic Fields.

PubMed

Henz, Diana; Schöllhorn, Wolfgang I; Poeggeler, Burkhard

2018-01-01

Recent neurophysiological studies indicate that exposure to electromagnetic fields (EMFs) generated by mobile phone radiation can exert effects on brain activity. One technical solution to reduce effects of EMFs in mobile phone use is provided in mobile phone chips that are applied to mobile phones or attached to their surfaces. To date, there are no systematical studies on the effects of mobile phone chip application on brain activity and the underlying neural mechanisms. The present study investigated whether mobile phone chips that are applied to mobile phones reduce effects of EMFs emitted by mobile phone radiation on electroencephalographic (EEG) brain activity in a laboratory study. Thirty participants volunteered in the present study. Experimental conditions (mobile phone chip, placebo chip, no chip) were set up in a randomized within-subjects design. Spontaneous EEG was recorded before and after mobile phone exposure for two 2-min sequences at resting conditions. During mobile phone exposure, spontaneous EEG was recorded for 30 min during resting conditions, and 5 min during performance of an attention test (d2-R). Results showed increased activity in the theta, alpha, beta and gamma bands during EMF exposure in the placebo and no chip conditions. Application of the mobile phone chip reduced effects of EMFs on EEG brain activity and attentional performance significantly. Attentional performance level was maintained regarding number of edited characters. Further, a dipole analysis revealed different underlying activation patterns in the chip condition compared to the placebo chip and no chip conditions. Finally, a correlational analysis for the EEG frequency bands and electromagnetic high-frequency (HF) emission showed significant correlations in the placebo chip and no chip condition for the theta, alpha, beta, and gamma bands. In the chip condition, a significant correlation of HF with the theta and alpha bands, but not with the beta and gamma bands was

Mobile Phone Chips Reduce Increases in EEG Brain Activity Induced by Mobile Phone-Emitted Electromagnetic Fields

PubMed Central

Henz, Diana; Schöllhorn, Wolfgang I.; Poeggeler, Burkhard

2018-01-01

Recent neurophysiological studies indicate that exposure to electromagnetic fields (EMFs) generated by mobile phone radiation can exert effects on brain activity. One technical solution to reduce effects of EMFs in mobile phone use is provided in mobile phone chips that are applied to mobile phones or attached to their surfaces. To date, there are no systematical studies on the effects of mobile phone chip application on brain activity and the underlying neural mechanisms. The present study investigated whether mobile phone chips that are applied to mobile phones reduce effects of EMFs emitted by mobile phone radiation on electroencephalographic (EEG) brain activity in a laboratory study. Thirty participants volunteered in the present study. Experimental conditions (mobile phone chip, placebo chip, no chip) were set up in a randomized within-subjects design. Spontaneous EEG was recorded before and after mobile phone exposure for two 2-min sequences at resting conditions. During mobile phone exposure, spontaneous EEG was recorded for 30 min during resting conditions, and 5 min during performance of an attention test (d2-R). Results showed increased activity in the theta, alpha, beta and gamma bands during EMF exposure in the placebo and no chip conditions. Application of the mobile phone chip reduced effects of EMFs on EEG brain activity and attentional performance significantly. Attentional performance level was maintained regarding number of edited characters. Further, a dipole analysis revealed different underlying activation patterns in the chip condition compared to the placebo chip and no chip conditions. Finally, a correlational analysis for the EEG frequency bands and electromagnetic high-frequency (HF) emission showed significant correlations in the placebo chip and no chip condition for the theta, alpha, beta, and gamma bands. In the chip condition, a significant correlation of HF with the theta and alpha bands, but not with the beta and gamma bands was

Enhancement of Catalytic Activity of Reduced Graphene Oxide Via Transition Metal Doping Strategy

NASA Astrophysics Data System (ADS)

Lee, Hangil; Hong, Jung A.

2017-06-01

To compare the catalytic oxidation activities of reduced graphene oxide (rGO) and rGO samples doped with five different transition metals (TM-rGO), we determine their effects on the oxidation of L-cysteine (Cys) in aqueous solution by performing electrochemistry (EC) measurements and on the photocatalytic oxidation of Cys by using high-resolution photoemission spectroscopy (HRPES) under UV illumination. Our results show that Cr-, Fe-, and Co-doped rGO with 3+ charge states (stable oxide forms: Cr3+, Fe3+, and Co3+) exhibit enhanced catalytic activities that are due to the charge states of the doped metal ions as we compare them with Cr-, Fe-, and Co-doped rGO with 2+ charge states.

Shape-Dependent Activity of Ceria for Hydrogen Electro-Oxidation in Reduced-Temperature Solid Oxide Fuel Cells.

PubMed

Tong, Xiaofeng; Luo, Ting; Meng, Xie; Wu, Hao; Li, Junliang; Liu, Xuejiao; Ji, Xiaona; Wang, Jianqiang; Chen, Chusheng; Zhan, Zhongliang

2015-11-04

Single crystalline ceria nanooctahedra, nanocubes, and nanorods are hydrothermally synthesized, colloidally impregnated into the porous La0.9Sr0.1Ga0.8Mg0.2O3-δ (LSGM) scaffolds, and electrochemically evaluated as the anode catalysts for reduced temperature solid oxide fuel cells (SOFCs). Well-defined surface terminations are confirmed by the high-resolution transmission electron microscopy--(111) for nanooctahedra, (100) for nanocubes, and both (110) and (100) for nanorods. Temperature-programmed reduction in H2 shows the highest reducibility for nanorods, followed sequentially by nanocubes and nanooctahedra. Measurements of the anode polarization resistances and the fuel cell power densities reveal different orders of activity of ceria nanocrystals at high and low temperatures for hydrogen electro-oxidation, i.e., nanorods > nanocubes > nanooctahedra at T ≤ 450 °C and nanooctahedra > nanorods > nanocubes at T ≥ 500 °C. Such shape-dependent activities of these ceria nanocrystals have been correlated to their difference in the local structure distortions and thus in the reducibility. These findings will open up a new strategy for design of advanced catalysts for reduced-temperature SOFCs by elaborately engineering the shape of nanocrystals and thus selectively exposing the crystal facets. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supporting aboriginal knowledge and practice in health care: lessons from a qualitative evaluation of the strong women, strong babies, strong culture program.

PubMed

Lowell, Anne; Kildea, Sue; Liddle, Marlene; Cox, Barbara; Paterson, Barbara

2015-02-05

The Strong Women, Strong Babies, Strong Culture Program (the Program) evolved from a recognition of the value of Aboriginal knowledge and practice in promoting maternal and child health (MCH) in remote communities of the Northern Territory (NT) of Australia. Commencing in 1993 it continues to operate today. In 2008, the NT Department of Health commissioned an evaluation to identify enabling factors and barriers to successful implementation of the Program, and to identify potential pathways for future development. In this paper we focus on the evaluation findings related specifically to the role of Aborignal cultural knowledge and practice within the Program. A qualitative evaluation utilised purposive sampling to maximise diversity in program history and Aboriginal culture. Semi-structured, in-depth interviews with 76 participants were recorded in their preferred language with a registered Interpreter when required. Thematic analysis of data was verified or modified through further discussions with participants and members of the evaluation team. Although the importance of Aboriginal knowledge and practice as a fundamental component of the Program is widely acknowledged, there has been considerable variation across time and location in the extent to which these cultural dimensions have been included in practice. Factors contributing to this variation are complex and relate to a number of broad themes including: location of control over Program activities; recognition and respect for Aboriginal knowledge and practice as a legitimate component of health care; working in partnership; communication within and beyond the Program; access to transport and working space; and governance and organisational support. We suggest that inclusion of Aboriginal knowledge and practice as a fundamental component of the Program is key to its survival over more than twenty years despite serious challenges. Respect for the legitimacy of Aboriginal knowledge and practice within health

Tensile and impact behaviour of BATMAN II steels, Ti-bearing reduced activation martensitic alloys

NASA Astrophysics Data System (ADS)

Filacchioni, G.; Casagrande, E.; De Angelis, U.; De Santis, G.; Ferrara, D.; Pilloni, L.

Two series of Reduced Activation Ferrous alloys (RAF) have been produced and studied by Casaccia's Laboratories. These martensitic alloys are named BATMAN steels. They are among the few presently developed RAF materials to exploit Ti as a carbide forming and grain size stabilizing element instead of Ta. In this work their mechanical properties are illustrated.

Recent status and improvement of reduced-activation ferritic-martensitic steels for high-temperature service

DOE PAGES

Tan, L.; Katoh, Y.; Tavassoli, A. -A. F.; ...

2016-07-26

Reduced-activation ferritic-martensitic (RAFM) steels, candidate structural materials for fusion reactors, have achieved technological maturity after about three decades of research and development. The recent status of a few developmental aspects of current RAFM steels, such as aging resistance, plate thickness effects, fracture toughness, and fatigue, is updated in this paper, together with ongoing efforts to develop next-generation RAFM steels for superior high-temperature performance. Additionally, to thermomechanical treatments, including nonstandard heat treatment, alloy chemistry refinements and modifications have demonstrated some improvements in high-temperature performance. Castable nanostructured alloys (CNAs) were developed by significantly increasing the amount of nanoscale MX (M = V/Ta/Ti,more » X = C/N) precipitates and reducing coarse M 23C 6 (M = Cr). Preliminary results showed promising improvement in creep resistance and Charpy impact toughness. We present and compare limited low-dose neutron irradiation results for one of the CNAs and China low activation martensitic with data for F82H and Eurofer97 irradiated up to ~70 displacements per atom at ~300–325 °C.« less

The Prescribed Amount of Physical Activity in Randomized Clinical Trials in Older Adults

ERIC Educational Resources Information Center

Kruger, Judy; Buchner, David M.; Prohaska, Thomas R.

2009-01-01

Purpose: Over the past two decades, a consensus has formed that increasing physical activity and reducing sedentary behavior in older adults are important for physical and cognitive health. Although there is strong evidence that regular physical activity can prevent or delay the onset of many chronic diseases, a major concern is ensuring that…

Wave propagation in strongly dispersive superthermal dusty plasma

NASA Astrophysics Data System (ADS)

El-Labany, S. K.; El-Shewy, E. K.; Abd El-Razek, H. N.; El-Rahman, A. A.

2017-04-01

The attributes of acoustic envelope waves in a collisionless dust ion unmagnetized plasmas model composed of cold ions, superthermal electrons and positive-negative dust grains have been studied. Using the derivative expansion technique in a strong dispersive medium, the system model is reduced to a nonlinearly form of Schrodinger equation (NLSE). Rational solution of NLSE in unstable region is responsible for the creation of large shape waves; namely rogue waves. The subjection of instability regions upon electron superthermality (via κ), carrier wave number and dusty grains charge is discussed.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint.

PubMed

Erdle, Benjamin; Herrmann, Simon; Porichis, Stella; Uhl, Markus; Ghanem, Nadir; Schmal, Hagen; Suedkamp, Norbert; Niemeyer, Philipp; Salzmann, Gian M

2017-10-01

Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. Case series; Level of evidence, 4. Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients' level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm 2 , and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated

Thrombin-activable fibrinolysis inhibitor attenuates (DD)E-mediated stimulation of plasminogen activation by reducing the affinity of (DD)E for tissue plasminogen activator. A potential mechanism for enhancing the fibrin specificity of tissue plasminogen activator.

PubMed

Stewart, R J; Fredenburgh, J C; Rischke, J A; Bajzar, L; Weitz, J I

2000-11-24

A complex of d-dimer noncovalently associated with fragment E ((DD)E), a degradation product of cross-linked fibrin that binds tissue plasminogen activator (t-PA) and plasminogen (Pg) with affinities similar to those of fibrin, compromises the fibrin specificity of t-PA by stimulating systemic Pg activation. In this study, we examined the effect of thrombin-activable fibrinolysis inhibitor (TAFI), a latent carboxypeptidase B (CPB)-like enzyme, on the stimulatory activity of (DD)E. Incubation of (DD)E with activated TAFI (TAFIa) or CPB (a) produces a 96% reduction in the capacity of (DD)E to stimulate t-PA-mediated activation of Glu- or Lys-Pg by reducing k(cat) and increasing K(m) for the reaction; (b) induces the release of 8 mol of lysine/mol of (DD)E, although most of the stimulatory activity is lost after release of only 4 mol of lysine/mol (DD)E; and (c) reduces the affinity of (DD)E for Glu-Pg, Lys-Pg, and t-PA by 2-, 4-, and 160-fold, respectively. Because TAFIa- or CPB-exposed (DD)E produces little stimulation of Glu-Pg activation by t-PA, (DD)E is not degraded into fragment E and d-dimer, the latter of which has been reported to impair fibrin polymerization. These data suggest a novel role for TAFIa. By attenuating systemic Pg activation by (DD)E, TAFIa renders t-PA more fibrin-specific.

A peptide derived from enzymatic digestion of globulins from amaranth shows strong affinity binding to the replication origin of Tomato yellow leaf curl virus reducing viral replication in Nicotiana benthamiana.

PubMed

Mendoza-Figueroa, J S; Kvarnheden, A; Méndez-Lozano, J; Rodríguez-Negrete, E-A; Arreguín-Espinosa de Los Monteros, R; Soriano-García, M

2018-02-01

Tomato yellow leaf curl virus (TYLCV; genus Begomovirus; family Geminiviridae) infects mainly plants of the family Solanaceae, and the infection induces curling and chlorosis of leaves, dwarfing of the whole plant, and reduced fruit production. Alternatives for direct control of TYLCV and other geminiviruses have been reported, for example, the use of esterified whey proteins, peptide aptamer libraries or artificial zinc finger proteins. The two latter alternatives affect directly the replication of TYLCV as well as of other geminiviruses because the replication structures and sequences are highly conserved within this virus family. Because peptides and proteins offer a potential solution for virus replication control, in this study we show the isolation, biochemical characterization and antiviral activity of a peptide derived from globulins of amaranth seeds (Amaranthus hypochondriacus) that binds to the replication origin sequence (OriRep) of TYLCV and affects viral replication with a consequent reduction of disease symptoms in Nicotiana benthamiana. Aromatic peptides obtained from papain digests of extracted globulins and albumins of amaranth were tested by intrinsic fluorescent titration and localized surface resonance plasmon to analyze their binding affinity to OriRep of TYLCV. The peptide AmPep1 (molecular weight 2.076 KDa) showed the highest affinity value (Kd = 1.8 nM) for OriRep. This peptide shares a high amino acid similarity with a part of an amaranth 11S globulin, and the strong affinity of AmPep1 could be explained by the presence of tryptophan and lysine facilitating interaction with the secondary structure of OriRep. In order to evaluate the effect of the peptide on in vitro DNA synthesis, rolling circle amplification (RCA) was performed using as template DNA from plants infected with TYLCV or another begomovirus, pepper huasteco yellow vein virus (PHYVV), and adding AmPep1 peptide at different concentrations. The results showed a decrease in

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

PubMed

Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

2015-10-01

Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Ebselen reduces autophagic activation and cell death in the ipsilateral thalamus following focal cerebral infarction.

PubMed

Li, Yiliang; Zhang, Jian; Chen, Li; Xing, Shihui; Li, Jingjing; Zhang, Yusheng; Li, Chuo; Pei, Zhong; Zeng, Jinsheng

2015-07-23

Previous studies have demonstrated that both oxidative stress and autophagy play important roles in secondary neuronal degeneration in the ipsilateral thalamus after distal middle cerebral artery occlusion (MCAO). This study aimed to investigate whether oxidative stress is associated with autophagy activation within the ipsilateral thalamus after distal MCAO. Sixty stroke-prone renovascular hypertensive rats were subjected to distal MCAO or sham operation, and were killed at 14 days after MCAO. Mn-SOD, LC3-II, Beclin-1 and p62 expression were evaluated by immunostaining and immunoblotting. Secondary damage in the thalamus was assessed with Nissl staining and immunostaining. The association of oxidative stress with autophagy activation was investigated by the antioxidant, ebselen. We found that treatment with ebselen at 24h after MCAO significantly reduced the expression of Mn-SOD in the ipsilateral thalamus at 14 days following focal cerebral infarction. In parallel, it prevented the elevation of LC3-II and Beclin-1, and the reduction of p62. Furthermore, ebselen attenuated the neuronal loss and gliosis in the ipsilateral thalamus. These results suggested that ebselen reduced oxidative stress, autophagy activation and secondary damage in the ipsilateral thalamus following MCAO. There are associations between oxidative stress, autophagy activation and secondary damage in the thalamus after MCAO. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection

PubMed Central

Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G.; Hunt, Peter; Yiannoutsos, Constantin T.; Spudich, Serena; Price, Richard W.

2012-01-01

Objective To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Design Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1–infected subjects divided into 3 groups: not on ART (termed “offs”), on ART with plasma HIV-1 RNA >500 copies/mL (“failures”), and on ART with plasma HIV-1 RNA ≤500 copies/mL (“successes”). T-cell activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. Results CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. Conclusions The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels. PMID:18362693

Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

PubMed Central

Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

2015-01-01

Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit.

PubMed

Li, Zhuang; Yi, Chun-Xia; Katiraei, Saeed; Kooijman, Sander; Zhou, Enchen; Chung, Chih Kit; Gao, Yuanqing; van den Heuvel, José K; Meijer, Onno C; Berbée, Jimmy F P; Heijink, Marieke; Giera, Martin; Willems van Dijk, Ko; Groen, Albert K; Rensen, Patrick C N; Wang, Yanan

2017-11-03

Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice. Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT. Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of Educational Activities in Reducing Pre-Analytical Laboratory Errors

PubMed Central

Al-Ghaithi, Hamed; Pathare, Anil; Al-Mamari, Sahimah; Villacrucis, Rodrigo; Fawaz, Naglaa; Alkindi, Salam

2017-01-01

Objectives Pre-analytic errors during diagnostic laboratory investigations can lead to increased patient morbidity and mortality. This study aimed to ascertain the effect of educational nursing activities on the incidence of pre-analytical errors resulting in non-conforming blood samples. Methods This study was conducted between January 2008 and December 2015. All specimens received at the Haematology Laboratory of the Sultan Qaboos University Hospital, Muscat, Oman, during this period were prospectively collected and analysed. Similar data from 2007 were collected retrospectively and used as a baseline for comparison. Non-conforming samples were defined as either clotted samples, haemolysed samples, use of the wrong anticoagulant, insufficient quantities of blood collected, incorrect/lack of labelling on a sample or lack of delivery of a sample in spite of a sample request. From 2008 onwards, multiple educational training activities directed at the hospital nursing staff and nursing students primarily responsible for blood collection were implemented on a regular basis. Results After initiating corrective measures in 2008, a progressive reduction in the percentage of non-conforming samples was observed from 2009 onwards. Despite a 127.84% increase in the total number of specimens received, there was a significant reduction in non-conforming samples from 0.29% in 2007 to 0.07% in 2015, resulting in an improvement of 75.86% (P <0.050). In particular, specimen identification errors decreased by 0.056%, with a 96.55% improvement. Conclusion Targeted educational activities directed primarily towards hospital nursing staff had a positive impact on the quality of laboratory specimens by significantly reducing pre-analytical errors. PMID:29062553

Suppressing unwanted memories reduces their unconscious influence via targeted cortical inhibition

PubMed Central

Gagnepain, Pierre; Henson, Richard N.; Anderson, Michael C.

2014-01-01

Suppressing retrieval of unwanted memories reduces their later conscious recall. It is widely believed, however, that suppressed memories can continue to exert strong unconscious effects that may compromise mental health. Here we show that excluding memories from awareness not only modulates medial temporal lobe regions involved in explicit retention, but also neocortical areas underlying unconscious expressions of memory. Using repetition priming in visual perception as a model task, we found that excluding memories of visual objects from consciousness reduced their later indirect influence on perception, literally making the content of suppressed memories harder for participants to see. Critically, effective connectivity and pattern similarity analysis revealed that suppression mechanisms mediated by the right middle frontal gyrus reduced activity in neocortical areas involved in perceiving objects and targeted the neural populations most activated by reminders. The degree of inhibitory modulation of the visual cortex while people were suppressing visual memories predicted, in a later perception test, the disruption in the neural markers of sensory memory. These findings suggest a neurobiological model of how motivated forgetting affects the unconscious expression of memory that may be generalized to other types of memory content. More generally, they suggest that the century-old assumption that suppression leaves unconscious memories intact should be reconsidered. PMID:24639546

Moderate-duration static stretch reduces active and passive plantar flexor moment but not Achilles tendon stiffness or active muscle length.

PubMed

Kay, Anthony D; Blazevich, Anthony J

2009-04-01

The effects of static stretch on muscle and tendon mechanical properties and muscle activation were studied in fifteen healthy human volunteers. Peak active and passive moment data were recorded during plantar flexion trials on an isokinetic dynamometer. Electromyography (EMG) monitoring of the triceps surae muscles, real-time motion analysis of the lower leg, and ultrasound imaging of the Achilles-medial gastrocnemius muscle-tendon junction were simultaneously conducted. Subjects performed three 60-s static stretches before being retested 2 min and 30 min poststretch. There were three main findings in the present study. First, peak concentric moment was significantly reduced after stretch; 60% of the deficit recovered 30 min poststretch. This was accompanied by, and correlated with (r = 0.81; P < 0.01) reductions in peak triceps surae EMG amplitude, which was fully recovered at 30 min poststretch. Second, Achilles tendon length was significantly shorter during the concentric contraction after stretch and at 30 min poststretch; however, no change in tendon stiffness was detected. Third, passive joint moment was significantly reduced after stretch, and this was accompanied by significant reductions in medial gastrocnemius passive muscle stiffness; both measures fully recovered by 30 min poststretch. These data indicate that the stretching protocol used in this study induced losses in concentric moment that were accompanied by, and related to, reductions in neuromuscular activity, but they were not associated with alterations in tendon stiffness or shorter muscle operating length. Reductions in passive moment were associated with reductions in muscle stiffness, whereas tendon mechanics were unaffected by the stretch. Importantly, the impact on mechanical properties and neuromuscular activity was minimal at 30 min poststretch.

Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.

PubMed

González, Alberto; Gutiérrez-Cutiño, Marlen; Moenne, Alejandra

2014-06-05

In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%), α-pinene (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and α-terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

PubMed

Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

2016-12-01

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

A Framework for the Validation of Probabilistic Seismic Hazard Analysis Maps Using Strong Ground Motion Data

NASA Astrophysics Data System (ADS)

Bydlon, S. A.; Beroza, G. C.

2015-12-01

Recent debate on the efficacy of Probabilistic Seismic Hazard Analysis (PSHA), and the utility of hazard maps (i.e. Stein et al., 2011; Hanks et al., 2012), has prompted a need for validation of such maps using recorded strong ground motion data. Unfortunately, strong motion records are limited spatially and temporally relative to the area and time windows hazard maps encompass. We develop a framework to test the predictive powers of PSHA maps that is flexible with respect to a map's specified probability of exceedance and time window, and the strong motion receiver coverage. Using a combination of recorded and interpolated strong motion records produced through the ShakeMap environment, we compile a record of ground motion intensity measures for California from 2002-present. We use this information to perform an area-based test of California PSHA maps inspired by the work of Ward (1995). Though this framework is flexible in that it can be applied to seismically active areas where ShakeMap-like ground shaking interpolations have or can be produced, this testing procedure is limited by the relatively short lifetime of strong motion recordings and by the desire to only test with data collected after the development of the PSHA map under scrutiny. To account for this, we use the assumption that PSHA maps are time independent to adapt the testing procedure for periods of recorded data shorter than the lifetime of a map. We note that accuracy of this testing procedure will only improve as more data is collected, or as the time-horizon of interest is reduced, as has been proposed for maps of areas experiencing induced seismicity. We believe that this procedure can be used to determine whether PSHA maps are accurately portraying seismic hazard and whether discrepancies are localized or systemic.

PREFACE: Strongly Coupled Coulomb Systems Strongly Coupled Coulomb Systems

NASA Astrophysics Data System (ADS)

Neilson, David; Senatore, Gaetano

2009-05-01

This special issue contains papers presented at the International Conference on Strongly Coupled Coulomb Systems (SCCS), held from 29 July-2 August 2008 at the University of Camerino. Camerino is an ancient hill-top town located in the Apennine mountains of Italy, 200 kilometres northeast of Rome, with a university dating back to 1336. The Camerino conference was the 11th in a series which started in 1977: 1977: Orleans-la-Source, France, as a NATO Advanced Study Institute on Strongly Coupled Plasmas (hosted by Marc Feix and Gabor J Kalman) 1982: Les Houches, France (hosted by Marc Baus and Jean-Pierre Hansen) 1986: Santa Cruz, California, USA (hosted by Forrest J Rogers and Hugh E DeWitt) 1989: Tokyo, Japan (hosted by Setsuo Ichimaru) 1992: Rochester, New York, USA (hosted by Hugh M Van Horn and Setsuo Ichimaru) 1995: Binz, Germany (hosted by Wolf Dietrich Kraeft and Manfred Schlanges) 1997: Boston, Massachusetts, USA (hosted by Gabor J Kalman) 1999: St Malo, France (hosted by Claude Deutsch and Bernard Jancovici) 2002: Santa Fe, New Mexico, USA (hosted by John F Benage and Michael S Murillo) 2005: Moscow, Russia (hosted by Vladimir E Fortov and Vladimir Vorob'ev). The name of the series was changed in 1996 from Strongly Coupled Plasmas to Strongly Coupled Coulomb Systems to reflect a wider range of topics. 'Strongly Coupled Coulomb Systems' encompasses diverse many-body systems and physical conditions. The purpose of the conferences is to provide a regular international forum for the presentation and discussion of research achievements and ideas relating to a variety of plasma, liquid and condensed matter systems that are dominated by strong Coulomb interactions between their constituents. Each meeting has seen an evolution of topics and emphases that have followed new discoveries and new techniques. The field has continued to see new experimental tools and access to new strongly coupled conditions, most recently in the areas of warm matter, dusty plasmas

Does Using a Chair Backrest or Reducing Seated Hip Flexion Influence Trunk Muscle Activity and Discomfort? A Systematic Review.

PubMed

Curran, Máire; O'Sullivan, Leonard; O'Sullivan, Peter; Dankaerts, Wim; O'Sullivan, Kieran

2015-11-01

This paper systematically reviews the effect of chair backrests and reducing seated hip flexion on low back discomfort (LBD) and trunk muscle activation. Prolonged sitting commonly exacerbates low back pain (LBP). Several modifications to seated posture and chair design have been recommended, including using chairs with backrests and chairs that reduce hip flexion. Electronic databases were searched by two independent assessors. Part 1 of this review includes 26 studies comparing the effect of sitting with at least two different hip angles. In Part 2, seven studies that compared the effect of sitting with and without a backrest were eligible. Study quality was assessed using the PEDro scale. Significant confounding variables and a relatively small number of randomized controlled trials (RCTs) involving people with LBP complicates analysis of the results. There was moderate evidence that chair backrests reduce paraspinal muscle activation, and limited evidence that chair backrests reduce LBD. There was no evidence that chairs involving less hip flexion reduce LBP or LBD, or consistently alter trunk muscle activation. However, participants in several studies subjectively preferred the modified chairs involving less hip flexion. The limited evidence to support the use of chairs involving less seated hip flexion, or the effect of a backrest, is consistent with the limited evidence that other isolated chair design features can reduce LBP. LBP management is likely to require consideration of several factors in addition to sitting position. Larger RCTs involving people with LBP are required. © 2015, Human Factors and Ergonomics Society.

Magnetic moments induce strong phonon renormalization in FeSi.

PubMed

Krannich, S; Sidis, Y; Lamago, D; Heid, R; Mignot, J-M; Löhneysen, H v; Ivanov, A; Steffens, P; Keller, T; Wang, L; Goering, E; Weber, F

2015-11-27

The interactions of electronic, spin and lattice degrees of freedom in solids result in complex phase diagrams, new emergent phenomena and technical applications. While electron-phonon coupling is well understood, and interactions between spin and electronic excitations are intensely investigated, only little is known about the dynamic interactions between spin and lattice excitations. Noncentrosymmetric FeSi is known to undergo with increasing temperature a crossover from insulating to metallic behaviour with concomitant magnetic fluctuations, and exhibits strongly temperature-dependent phonon energies. Here we show by detailed inelastic neutron-scattering measurements and ab initio calculations that the phonon renormalization in FeSi is linked to its unconventional magnetic properties. Electronic states mediating conventional electron-phonon coupling are only activated in the presence of strong magnetic fluctuations. Furthermore, phonons entailing strongly varying Fe-Fe distances are damped via dynamic coupling to the temperature-induced magnetic moments, highlighting FeSi as a material with direct spin-phonon coupling and multiple interaction paths.

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

PubMed Central

Martinez-Lopez, Alicia; Encinar, Jose Antonio; Medina-Gali, Regla Maria; Balseiro, Pablo; Garcia-Valtanen, Pablo; Figueras, Antonio; Novoa, Beatriz; Estepa, Amparo

2013-01-01

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”. PMID:23880927

Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

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

Zhou, Haibin; Aguilar, Angelo; Chen, Jianfang

Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 {angstrom} resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K{sub i} values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC{sub 50} values in multiple small-cell lung cancer cellmore » lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.« less

Improving the activity of rutile titanium dioxide with reduced graphene oxide

NASA Astrophysics Data System (ADS)

Yuliati, Leny; Alim, Nor Shuhada; Lintang, Hendrik O.

2017-11-01

Among titanium dioxide (TiO2), rutile is the most stable polymorph of TiO2 at all temperatures. However, its application as photocatalyst is less explored since generally anatase and anatase-rutile mixture show better photocatalytic activity than the rutile structure. In this study, we successfully improved the photocatalytic activity of rutile up to four times higher when it was modified with reduced graphene oxide (rGO). The rGO-TiO2 composites were prepared by photocatalytic reduction of graphene oxide (GO) at room temperature under ultraviolet (UV) light irradiation in the presence of rutile TiO2. The amount of GO which was prepared by oxidation of graphite flakes via the Hummers' method was varied from 0.5 to 5 wt%. The properties of the obtained composites were investigated by several characterization methods. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopies revealed that the rGO-TiO2 composites could be prepared without disrupting the structure of rutile TiO2. The fluorescence spectroscopy confirmed that the presence of rGO decreased the emission intensity of rutile TiO2, suggesting that the interactions between the rGO and the rutile TiO2 might cause the decrease in electron-hole recombination on the TiO2. The activity of the composites was evaluated for degradation of phenol under UV light irradiation for 3 h. It was observed that the addition of small amount of rGO (1 wt% GO) significantly improved the photocatalytic activity of rutile TiO2.

Reducing Capacities and Distribution of Redox-Active Functional Groups in Low Molecular Weight Fractions of Humic Acids.

PubMed

Yang, Zhen; Kappler, Andreas; Jiang, Jie

2016-11-15

Humic substances (HS) are redox-active organic compounds with a broad spectrum of molecular sizes and reducing capacities, that is, number of electrons donated or accepted. However, it is unknown which role the distribution of redox-active functional groups in different molecule sizes plays for HS redox reactions in varying pore sizes microenvironments. We used dialysis experiments to separate bulk humic acids (HA) into low molecular weight fractions (LMWF) and retentate, for example, the remaining HA in the dialysis bag. LMWF accounted for only 2% of the total organic carbon content of the HA. However, their reducing capacities per gram of carbon were up to 33 times greater than either those of the bulk HA or the retentate. For a structural/mechanistic understanding of the high reducing capacity of the LMWF, we used fluorescence spectroscopy. We found that the LWMF showed significant fluorescence intensities for quinone-like functional groups, as indicated by the quinoid π-π* transition, that are probably responsible for the high reducing capacities. Therefore, the small-sized HS fraction can play a major role for redox transformation of metals or pollutants trapped in soil micropores (<2.5 nm diameter).

Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus.

PubMed

The, Fo; Cailotto, C; van der Vliet, J; de Jonge, W J; Bennink, R J; Buijs, R M; Boeckxstaens, G E

2011-07-01

Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg(-1) ) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity.

PubMed

Takáts, Szabolcs; Varga, Ágnes; Pircs, Karolina; Juhász, Gábor

2015-01-01

The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals. Thus, Vps16A reduces autophagosome numbers both by indirectly restricting their formation rate and by directly promoting their clearance. In contrast, the loss of Syx17 blocks autophagic flux without affecting the induction step in Drosophila.

Activation of aluminum as an effective reducing agent by pitting corrosion for wet-chemical synthesis.

PubMed

Li, Wei; Cochell, Thomas; Manthiram, Arumugam

2013-01-01

Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F⁻, Cl⁻, and Br⁻ in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu₂Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent.

Accretion disc dynamo activity in local simulations spanning weak-to-strong net vertical magnetic flux regimes

NASA Astrophysics Data System (ADS)

Salvesen, Greg; Simon, Jacob B.; Armitage, Philip J.; Begelman, Mitchell C.

2016-03-01

Strongly magnetized accretion discs around black holes have attractive features that may explain enigmatic aspects of X-ray binary behaviour. The structure and evolution of these discs are governed by a dynamo-like mechanism, which channels part of the accretion power liberated by the magnetorotational instability (MRI) into an ordered toroidal magnetic field. To study dynamo activity, we performed three-dimensional, stratified, isothermal, ideal magnetohydrodynamic shearing box simulations. The strength of the self-sustained toroidal magnetic field depends on the net vertical magnetic flux, which we vary across almost the entire range over which the MRI is linearly unstable. We quantify disc structure and dynamo properties as a function of the initial ratio of mid-plane gas pressure to vertical magnetic field pressure, β _0^mid = p_gas / p_B. For 10^5 ≥ β _0^mid ≥ 10 the effective α-viscosity parameter scales as a power law. Dynamo activity persists up to and including β _0^mid = 10^2, at which point the entire vertical column of the disc is magnetic pressure dominated. Still stronger fields result in a highly inhomogeneous disc structure, with large density fluctuations. We show that the turbulent steady state βmid in our simulations is well matched by the analytic model of Begelman et al. describing the creation and buoyant escape of toroidal field, while the vertical structure of the disc can be broadly reproduced using this model. Finally, we discuss the implications of our results for observed properties of X-ray binaries.

Vav1 GEF activity is required for T cell mediated allograft rejection.

PubMed

Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

2012-06-01

The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

Vav1 GEF activity is required for T cell mediated allograft rejection

PubMed Central

Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L.J.; Weckbecker, Gisbert

2012-01-01

The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. PMID:22456277

Protease-Activated Receptor 4 Variant p.Tyr157Cys Reduces Platelet Functional Responses and Alters Receptor Trafficking.

PubMed

Norman, Jane E; Cunningham, Margaret R; Jones, Matthew L; Walker, Mary E; Westbury, Sarah K; Sessions, Richard B; Mundell, Stuart J; Mumford, Andrew D

2016-05-01

Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by F2RL3, which has abundant rare missense variants. We aimed to provide proof of principle that rare F2LR3 variants potentially affect platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms. We identified 6 rare F2RL3 missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to have the greatest effect on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective N-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells. Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists. © 2016 American Heart Association, Inc.

A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease.

PubMed

Trasino, Steven E; Tang, Xiao-Han; Jessurun, Jose; Gudas, Lorraine J

2016-10-01

Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). Kupffer cell (macrophage) expression of transforming growth factor-β1 (TGF-β1), which plays a critical role in early HSC activation, was markedly reduced in AC261066-treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARγ agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-β1 levels. In conclusion, our data demonstrate that RARβ2 is an attractive target for development of NAFLD therapies. • Hepatic stellate cells (HSCs) are an important pharmacological target for the prevention of nonalcoholic fatty liver diseases (NAFLD). • Retinoids and retinoic acid receptors (RARs) possess favorable metabolic modulating properties. • We show that an agonist for retinoic acid receptor-β2 (RARβ2), but not RARγ, mitigates HSC activation and NAFLD.

Pesticide seed dressings can affect the activity of various soil organisms and reduce decomposition of plant material.

PubMed

Zaller, Johann G; König, Nina; Tiefenbacher, Alexandra; Muraoka, Yoko; Querner, Pascal; Ratzenböck, Andreas; Bonkowski, Michael; Koller, Robert

2016-08-17

Seed dressing with pesticides is widely used to protect crop seeds from pest insects and fungal diseases. While there is mounting evidence that especially neonicotinoid seed dressings detrimentally affect insect pollinators, surprisingly little is known on potential side effects on soil biota. We hypothesized that soil organisms would be particularly susceptible to pesticide seed dressings as they get in direct contact with these chemicals. Using microcosms with field soil we investigated, whether seeds treated either with neonicotinoid insecticides or fungicides influence the activity and interaction of earthworms, collembola, protozoa and microorganisms. The full-factorial design consisted of the factor Seed dressing (control vs. insecticide vs. fungicide), Earthworm (no earthworms vs. addition Lumbricus terrestris L.) and collembola (no collembola vs. addition Sinella curviseta Brook). We used commercially available wheat seed material (Triticum aesticum L. cf. Lukullus) at a recommended seeding density of 367 m(-2). Seed dressings (particularly fungicides) increased collembola surface activity, increased the number of protozoa and reduced plant decomposition rate but did not affect earthworm activity. Seed dressings had no influence on wheat growth. Earthworms interactively affected the influence of seed dressings on collembola activity, whereas collembola increased earthworm surface activity but reduced soil basal respiration. Earthworms also decreased wheat growth, reduced soil basal respiration and microbial biomass but increased soil water content and electrical conductivity. The reported non-target effects of seed dressings and their interactions with soil organisms are remarkable because they were observed after a one-time application of only 18 pesticide treated seeds per experimental pot. Because of the increasing use of seed dressing in agriculture and the fundamental role of soil organisms in agroecosystems these ecological interactions should

Surface modification and deuterium retention in reduced-activation steels under low-energy deuterium plasma exposure. Part I: undamaged steels

NASA Astrophysics Data System (ADS)

Ogorodnikova, O. V.; Zhou, Z.; Sugiyama, K.; Balden, M.; Gasparyan, Yu.; Efimov, V.

2017-03-01

In this paper, reduced-activation ferritic/martensitic (RAFM) steels including Eurofer (9Cr) and oxide dispersion strengthening (ODS) steels by the addition of Y2O3 particles with different amounts of Cr, namely, (9-16)Cr were exposed to low energy deuterium (D) plasma (~20-200 eV per D) up to a fluence of 2.9  ×  1025 D m-2 in the temperature range from 290 K to 700 K. The depth profile of D in steels was measured up to 8 µm depth by nuclear reaction analysis (NRA) and the total retained amount of D in those materials was determined by thermal desorption spectroscopy (TDS). It was found that the D retention in ODS steels is higher compared to Eurofer due to the much higher density of fine dispersoids and finer grain size. This work shows that in addition to the sintering temperature and time, the type, size and concentration of the doping particles have an enormous effect on the increase in the D retention. The D retention in undamaged ODS steels strongly depends on the Cr content: ODS with 12Cr has a minimum and the D retention in the case of ODS with (14-16)Cr is higher compared to (9-12)Cr. The replacing of Ti by Al in ODS-14Cr steels reduces the D retention. The formation of nano-structure surface roughness enriched in W or Ta due to combination of preferential sputtering of light elements and radiation-induced segregation was observed at incident D ion energy of 200 eV for both Eurofer and ODS steels. Both the surface roughness and the eroded layer enhance with increasing the temperature. The surface modifications result in a reduction of the D retention near the surface due to increasing the desorption flux and can reduce the overall D retention.

Amygdala lesions reduce cataplexy in orexin knock-out mice.

PubMed

Burgess, Christian R; Oishi, Yo; Mochizuki, Takatoshi; Peever, John H; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.

Rapid assay for microbially reducible ferric iron in aquatic sediments

USGS Publications Warehouse

Lovely, Derek R.; Philips , Elizabeth J.P.

1987-01-01

The availability of ferric iron for microbial reduction as directly determined by the activity of iron-reducing organisms was compared with its availability as determined by a newly developed chemical assay for microbially reducible iron. The chemical assay was based on the reduction of poorly crystalline ferric iron by hydroxylamine under acidic conditions. There was a strong correlation between the extent to which hydroxylamine could reduce various synthetic ferric iron forms and the susceptibility of the iron to microbial reduction in an enrichment culture of iron-reducing organisms. When sediments that contained hydroxylamine-reducible ferric iron were incubated under anaerobic conditions, ferrous iron accumulated as the concentration of hydroxylamine-reducible ferric iron declined over time. Ferrous iron production stopped as soon as the hydroxylamine-reducible ferric iron was depleted. In anaerobic incubations of reduced sediments that did not contain hydroxylamine-reducible ferric iron, there was no microbial iron reduction, even though the sediments contained high concentrations of oxalate-extractable ferric iron. A correspondence between the presence of hydroxylamine-reducible ferric iron and the extent of ferric iron reduction in anaerobic incubations was observed in sediments from an aquifer and in fresh- and brackish-water sediments from the Potomac River estuary. The assay is a significant improvement over previously described procedures for the determination of hydroxylamine-reducible ferric iron because it provides a correction for the high concentrations of solid ferrous iron which may also be extracted from sediments with acid. This is a rapid, simple technique to determine whether ferric iron is available for microbial reduction.

Higher order mode laser beam intensity fluctuations in strong oceanic turbulence

NASA Astrophysics Data System (ADS)

Baykal, Yahya

2017-05-01

Intensity fluctuations of the higher order mode laser beams are evaluated when these beams propagate in a medium exhibiting strong oceanic turbulence. Our formulation involves the modified Rytov solution that extends the Rytov solution to cover strong turbulence as well, and our recently reported expression that relates the atmospheric turbulence structure constant to the oceanic turbulence parameters and oceanic wireless optical communication link parameters. The variations of the intensity fluctuations are reported against the changes of the ratio of temperature to salinity contributions to the refractive index spectrum, rate of dissipation of kinetic energy per unit mass of fluid, rate of dissipation of mean-squared temperature, viscosity and the source size of the higher order mode laser beam. Our results indicate that under any oceanic turbulence parameters, it is advantageous to employ higher order laser modes in reducing the scintillation noise in wireless optical communication links operating in a strongly turbulent ocean.

Activation of CO2-reducing methanogens in oil reservoir after addition of nutrient.

PubMed

Yang, Guang-Chao; Zhou, Lei; Mbadinga, Serge Maurice; You, Jing; Yang, Hua-Zhen; Liu, Jin-Feng; Yang, Shi-Zhong; Gu, Ji-Dong; Mu, Bo-Zhong

2016-12-01

Nutrient addition as part of microbial enhanced oil recovery (MEOR) operations have important implications for more energy recovery from oil reservoirs, but very little is known about the in situ response of microorganisms after intervention. An analysis of two genes as biomarkers, mcrA encoding the key enzyme in methanogenesis and fthfs encoding the key enzyme in acetogenesis, was conducted during nutrient addition in oil reservoir. Clone library data showed that dominant mcrA sequences changed from acetoclastic (Methanosaetaceae) to CO 2 -reducing methanogens (Methanomicrobiales and Methanobacteriales), and the authentic acetogens affiliated to Firmicutes decreased after the intervention. Principal coordinates analysis (PCoA) and Jackknife environment clusters revealed evidence on the shift of the microbial community structure among the samples. Quantitative analysis of methanogens via qPCR showed that Methanobacteriales and Methanomicrobiales increased after nutrient addition, while acetoclastic methanogens (Methanosaetaceae) changed slightly. Nutrient treatment activated native CO 2 -reducing methanogens in oil reservoir. The high frequency of Methanobacteriales and Methanomicrobiales (CO 2 -reducers) after nutrient addition in this petroleum system suggested that CO 2 -reducing methanogenesis was involved in methane production. The nutrient addition could promote the methane production. The results will likely improve strategies of utilizing microorganisms in subsurface environments. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Physical Activity and Weight Loss Reduce the Risk of Breast Cancer: A Meta-analysis of 139 Prospective and Retrospective Studies.

PubMed

Hardefeldt, Prue J; Penninkilampi, Ross; Edirimanne, Senarath; Eslick, Guy D

2017-10-17

Physical activity and weight loss have been shown to reduce breast cancer incidence in numerous observational studies. The aim of this meta-analysis was to assess the effect of both physical activity and weight loss on breast cancer incidence. Specifically, we aimed to complete subgroup analyses by the intensity of physical activity and menopausal status at breast cancer diagnosis to further elucidate the relationship between physical activity, weight loss, and breast cancer incidence. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google Scholar through November 5, 2017. A random-effects model was used for pooled data. There were 139 studies included in the meta-analysis, including 236,955 cases and 3,963,367 controls. Physical activity significantly reduced the risk of breast cancer (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.76-0.81; P < .001), with high-intensity physical activity being slightly more protective (OR, 0.73; 95% CI, 0.65-0.81; P < .001) than low-intensity exercise (OR, 0.79; 95% CI, 0.72-0.86; P < .001). The effect size for general exercise was similar in both premenopausal (OR, 0.79; 95% CI, 0.73-0.87; P < .001) and postmenopausal (OR, 0.82; 95% CI, 0.78-0.86; P < .001) women. Additionally, weight loss reduced the risk of breast cancer incidence (OR, 0.82; 95% CI, 0.67-0.97). Physical activity and weight loss significantly reduce the risk of breast cancer, irrespective of the timing and intensity of the exercise. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-08-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics |*| the infamous |*|gastrophysics|*| in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

NASA Astrophysics Data System (ADS)

Bayliss, Matthew

2017-09-01

We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics -- the infamous ``gastrophysics''-- in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

Synthesis of dendritic platinum nanoparticles/lucigenin/reduced graphene oxide hybrid with chemiluminescence activity.

PubMed

He, Yi; Cui, Hua

2012-04-16

Multifunctional hybrid: A dendritic platinum nanoparticle/lucigenin/reduced graphene oxide (RGO) hybrid with chemiluminescence (CL) activity was prepared for the first time by using lucigenin as a linker through simultaneous reduction of H(2) PtCl(4) and a lucigenin-functionalized graphene oxide composite by sodium borohydride (see scheme). The hybrid may have potential applications as a CL sensor, in catalysis, energy conversion, and opto-electronic systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled green synthesis of silver nanoparticles by Allium cepa and Musa acuminata with strong antimicrobial activity

NASA Astrophysics Data System (ADS)

Sahni, Geetika; Panwar, Amit; Kaur, Balpreet

2015-02-01

A controlled "green synthesis" approach to synthesize silver nanoparticles by Allium cepa and Musa acuminata plant extract has been reported. The effect of different process parameters, such as pH, temperature and time, on synthesis of Ag nanoparticles from plant extracts has been highlighted. The work reports an easy approach to control the kinetics of interaction of metal ions with reducing agents, stabilized by ammonia to achieve sub-10 nm particles with narrow size distribution. The nanoparticles have been characterized by UV-Visible spectra and TEM analysis. Excellent antimicrobial activity at extremely low concentration of the nanoparticles was observed against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Fusarium oxysporum which may allow their exploitation as a new generation nanoproduct in biomedical and agricultural applications.

Efficient CO2-Reducing Activity of NAD-Dependent Formate Dehydrogenase from Thiobacillus sp. KNK65MA for Formate Production from CO2 Gas

PubMed Central

Cho, Dae Haeng; Kim, Min Hoo; Lee, Sang Hyun; Jung, Kwang Deog; Kim, Yong Hwan

2014-01-01

NAD-dependent formate dehydrogenase (FDH) from Candida boidinii (CbFDH) has been widely used in various CO2-reduction systems but its practical applications are often impeded due to low CO2-reducing activity. In this study, we demonstrated superior CO2-reducing properties of FDH from Thiobacillus sp. KNK65MA (TsFDH) for production of formate from CO2 gas. To discover more efficient CO2-reducing FDHs than a reference enzyme, i.e. CbFDH, five FDHs were selected with biochemical properties and then, their CO2-reducing activities were evaluated. All FDHs including CbFDH showed better CO2-reducing activities at acidic pHs than at neutral pHs and four FDHs were more active than CbFDH in the CO2 reduction reaction. In particular, the FDH from Thiobacillus sp. KNK65MA (TsFDH) exhibited the highest CO2-reducing activity and had a dramatic preference for the reduction reaction, i.e., a 84.2-fold higher ratio of CO2 reduction to formate oxidation in catalytic efficiency (k cat/K B) compared to CbFDH. Formate was produced from CO2 gas using TsFDH and CbFDH, and TsFDH showed a 5.8-fold higher formate production rate than CbFDH. A sequence and structural comparison showed that FDHs with relatively high CO2-reducing activities had elongated N- and C-terminal loops. The experimental results demonstrate that TsFDH can be an alternative to CbFDH as a biocatalyst in CO2 reduction systems. PMID:25061666

Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in vitro and in vivo.

PubMed

Faraone, Debora; Aguzzi, Maria Simona; Toietta, Gabriele; Facchiano, Angelo M; Facchiano, Francesco; Magenta, Alessandra; Martelli, Fabio; Truffa, Silvia; Cesareo, Eleonora; Ribatti, Domenico; Capogrossi, Maurizio C; Facchiano, Antonio

2009-08-01

Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs) is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Ralpha may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Ralpha respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Ralpha. Proliferation was rescued by PDGF-Ralpha inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Ralpha mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Ralpha was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Ralpha show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Balpha and a marked increase of p38gamma, mitogen-activated protein kinase kinase 3, and signal regulatory protein alpha1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Ralpha reached a significant 70% inhibition of primary melanoma growth (P < .001) and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Ralpha strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control.

Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

PubMed

Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

2010-10-01

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation.

PubMed

Valencia-Torres, Lourdes; Olarte-Sánchez, Cristian M; Lyons, David J; Georgescu, Teodora; Greenwald-Yarnell, Megan; Myers, Martin G; Bradshaw, Christopher M; Heisler, Lora K

2017-06-01

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT 2C R) is a target for the treatment of human obesity. Mechanistically, 5-HT 2C Rs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT 2C Rs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT 2C R agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT 2C R expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT 2C R expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT 2C R CRE line to clarify the function of subset of 5-HT 2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT 2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT 2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT 2C R neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity.

Active Chest Tube Clearance After Cardiac Surgery Is Associated With Reduced Reexploration Rates.

PubMed

Grieshaber, Philippe; Heim, Nicolas; Herzberg, Moritz; Niemann, Bernd; Roth, Peter; Boening, Andreas

2018-06-01

Ineffective evacuation of intrathoracic fluid after cardiac surgery (retained blood syndrome [RBS]) might increase postoperative complications, morbidity, and mortality. Active tube clearance (ATC) technology using an intraluminal clearing apparatus aims at increasing chest tube drainage efficiency. This study evaluated whether ATC reduces RBS in an all-comers collective undergoing scheduled cardiac surgery with cardiopulmonary bypass and full or partial median sternotomy. In this nonrandomized prospective trial, 581 consecutive patients undergoing scheduled cardiac surgery with median sternotomy between January 2016 and December 2016 were assigned to receive conventional chest tubes (control group) or a combination of conventional tubes and as many as two ATC devices (ATC group), depending on their operation date. Postoperative occurrence of RBS (one or more of the following: reexploration for bleeding or tamponade, pericardial drainage procedure, pleural drainage procedure) and other endpoints were compared. Propensity score matching was applied. In 222 ATC patients and 222 matched control patients, RBS occurrence did not differ between the groups (ATC 16%, control 22%; p = 0.15). However, reexploration rate for bleeding or tamponade was significantly reduced in the ATC group compared with the control group (4.1% versus 9.1%, respectively; p = 0.015). The mortality of RBS patients (21%) was higher compared with patients without RBS (3.9%, p < 0.001). Among the RBS components, only reexploration (odds ratio 16, 95% confidence interval: 5.8 to 43, p < 0.001) was relevant for inhospital mortality (ATC 6.8%, control 7.7%; p = 0.71). Active tube clearance is associated with reduced reexploration rates in an all-comers collective undergoing cardiac surgery. Reexploration is the only RBS component relevant for mortality. The ATC effect does not translate into improved overall survival. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

PubMed Central

Valencia-Torres, Lourdes; Olarte-Sánchez, Cristian M; Lyons, David J; Georgescu, Teodora; Greenwald-Yarnell, Megan; Myers, Martin G; Bradshaw, Christopher M; Heisler, Lora K

2017-01-01

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT2CR agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT2CR expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT2CR expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT2CRCRE line to clarify the function of subset of 5-HT2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT2CR neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity. PMID:27882999

Shear stress reduces protease activated receptor-1 expression in human endothelial cells

NASA Technical Reports Server (NTRS)

Nguyen, K. T.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

2001-01-01

Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.

Platinum-doped titanate nanotubes/reduced graphene oxide: photocatalytic activity and flame retardancy

NASA Astrophysics Data System (ADS)

Liu, Guangya; Sang, Bin; Zhou, Zhiqi; Li, Zhiwei

2018-01-01

The ‘white pollution’ produced by wasted flexible polyvinyl chloride (PVC) with poor degradation ability and the potential fire hazard of PVC with high flammability not only restrict their application but also cause serious environmental problem. Thus platinum-doped titanate nanotubes/reduced graphene oxide (denoted as Pt-TNTs/rGO) nanocomposites were prepared by a facile method in order to improve the visible photodegradation and get rid of the ‘white pollution’ as well as flame retardancy of PVC. The photodegradation activity and flame retardancy effect of the as-prepared Pt-TNTs/rGO nanocomposites were investigated by ultraviolet and visible light irradiation as well as cone calorimetry. Results show that the Pt-TNTs/rGO-PVC nanocomposites exhibit enhanced visible light photodegradation performance (with mass loss being 6.5%) during 15 day exposure to solar irradiation, and good flame retardancy (providing a 44% reduction of total smoke release as compared with that of PVC matrix). Besides, Pt-TNTs/rGO-PVC nanocomposites show suppressed smoke and reduced CO production as compared with the PVC matrix. These results demonstrate that Pt-TNTs/rGO not only get rid of the ‘white pollution’ as the photocatalyst but also improve the fire safety of PVC as the flame retardant. This could be ascribed to the combination effect between Pt-TNTs and rGO. The present research, hopefully, is to pave a potential pathway to constructing polymer-matrix composites with desired photodegradation activity and flame retardancy, thereby shedding light on simultaneously dealing with the ‘white pollution’ and high flammability of polymer matrix like PVC.

Informing Investment to Reduce Inequalities: A Modelling Approach

PubMed Central

McAuley, Andrew; Denny, Cheryl; Taulbut, Martin; Mitchell, Rory; Fischbacher, Colin; Graham, Barbara; Grant, Ian; O’Hagan, Paul; McAllister, David; McCartney, Gerry

2016-01-01

Background Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and Methods Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions Interventions have markedly different effects on mortality, hospitalisations and

Informing Investment to Reduce Inequalities: A Modelling Approach.

PubMed

McAuley, Andrew; Denny, Cheryl; Taulbut, Martin; Mitchell, Rory; Fischbacher, Colin; Graham, Barbara; Grant, Ian; O'Hagan, Paul; McAllister, David; McCartney, Gerry

2016-01-01

Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. To provide estimates of the impact of a range of interventions on health and health inequalities. Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a 'living wage'; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Introduction of a 'living wage' generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for

Transmutation and activation of reduced activation ferritic martensitic steel in molten salt cooled fusion power plants

NASA Astrophysics Data System (ADS)

Cheng, E. T.

2004-08-01

Neutron activation analysis was conducted for the reduced activation ferritic/martensitic (RAFM) steel used in flibe molten-salt cooled fusion blankets. After 22.4 MW yr/m 2 of neutron exposure, the RAFM steel first wall in a molten salt blanket with 40% lithium-6 enrichment in lithium was found to be within 1 mSv/h in contact dose rate after 100 yr of cooling. The contact dose rate drops to 30 and 20 μSv/h or less, respectively, when the cooling times are 300 and 500 yr after discharge. The RAFM steel discharged from the high-temperature shield component would be allowed for hands-on recycling after 100 yr of cooling, when the contact dose rate is 10 μSv/h or less. The most significant changes found in the RAFM steel first wall due to nuclear transmutation, are 10% decrease in W and 10% increase in Ti. Additionally, there are minor elements produced: Mn - <1.2%, V - <0.26%, Re - <0.2%, Ta - <0.08%, and Os - <0.1%, all in weight percent. The gaseous elements generated are H and He, and the, respectively, accumulated quantities are about 260 and 190 wppm.

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

PubMed

Oberoi, Sapna; Robinson, Paula D; Cataudella, Danielle; Culos-Reed, S Nicole; Davis, Hailey; Duong, Nathan; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Cabral, Sandra; Dupuis, L Lee; Sung, Lillian

2018-02-01

Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority. Copyright © 2017 Elsevier B.V. All rights reserved.