Joint reconstruction of activity and attenuation in Time-of-Flight PET: A Quantitative Analysis.

PubMed

Rezaei, Ahmadreza; Deroose, Christophe M; Vahle, Thomas; Boada, Fernando; Nuyts, Johan

2018-03-01

Joint activity and attenuation reconstruction methods from time of flight (TOF) positron emission tomography (PET) data provide an effective solution to attenuation correction when no (or incomplete/inaccurate) information on the attenuation is available. One of the main barriers limiting their use in clinical practice is the lack of validation of these methods on a relatively large patient database. In this contribution, we aim at validating the activity reconstructions of the maximum likelihood activity reconstruction and attenuation registration (MLRR) algorithm on a whole-body patient data set. Furthermore, a partial validation (since the scale problem of the algorithm is avoided for now) of the maximum likelihood activity and attenuation reconstruction (MLAA) algorithm is also provided. We present a quantitative comparison of the joint reconstructions to the current clinical gold-standard maximum likelihood expectation maximization (MLEM) reconstruction with CT-based attenuation correction. Methods: The whole-body TOF-PET emission data of each patient data set is processed as a whole to reconstruct an activity volume covering all the acquired bed positions, which helps to reduce the problem of a scale per bed position in MLAA to a global scale for the entire activity volume. Three reconstruction algorithms are used: MLEM, MLRR and MLAA. A maximum likelihood (ML) scaling of the single scatter simulation (SSS) estimate to the emission data is used for scatter correction. The reconstruction results are then analyzed in different regions of interest. Results: The joint reconstructions of the whole-body patient data set provide better quantification in case of PET and CT misalignments caused by patient and organ motion. Our quantitative analysis shows a difference of -4.2% (±2.3%) and -7.5% (±4.6%) between the joint reconstructions of MLRR and MLAA compared to MLEM, averaged over all regions of interest, respectively. Conclusion: Joint activity and attenuation

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis.

PubMed

Khader, Adam; Yang, Weng-Lang; Hansen, Laura W; Rajayer, Salil R; Prince, Jose M; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

2017-11-01

Sepsis affects 800,000 patients in the United States annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis. Male C57BL/6 mice (20-25 g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2-mL saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) and renal injury markers (blood urea nitrogen and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines interleukin (IL)-1β and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components (nucleotide oligomerization domain-like receptor protein 3, adapter apoptosis-associated speck-like protein containing caspase-recruitment domain, IL-1β, and IL-18) in the liver, compared with the vehicle group. SRT1720 treatment attenuates multiorgan injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation

PubMed Central

Song, Dongmei; Song, Geng; Niu, Yinghao; Song, Wei; Wang, Jiantao; Yu, Lei; Yang, Jianwang; Lv, Xin; Steinberg, Harry; Liu, Shu Fang; Wang, Baoshan

2014-01-01

Background and Purpose Ulinastatin (UTI), a serine protease inhibitor, was recently found to have an anti-inflammatory action. However, the mechanisms mediating this anti-inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1). Experimental Approach Control mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI-induced HO1 expression in anti-inflammatory and antioxidant effects of UTI was also evaluated. Key Results UTI markedly increased basal HO1 protein expression in lungs of control mice in a time- and dose-dependent manner, and augmented HO1 protein expression induced by OVA. The up-regulation of HO1 mediated by UTI in sensitized and OVA-challenged mice was associated with reduced airway inflammation, alleviated tissue injury, reduced oxidant stress and enhanced antioxidant enzyme activities. Inhibition of HO1 activity using HO1 inhibitor, zinc protoporphyrin, attenuated inhibitory effects of UTI on inflammation and oxidant stress, and its stimulant effects on antioxidant enzyme activities. Mechanistic analysis showed that UTI increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), stimulated Nrf2 DNA binding activity and concomitantly up-regulated HO1 mRNA expression. Conclusions and Implications UTI is a potent and naturally occurring inducer of HO1 expression. HO1 up-regulation contributes significantly to the anti-inflammatory and organ-protective effects of UTI, which has important research and therapeutic implications. PMID:24835359

Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.

PubMed

Kleven, Mark S; Barret-Grévoz, Catherine; Bruins Slot, Liesbeth; Newman-Tancredi, Adrian

2005-08-01

Compounds possessing 5-HT(1A) agonist properties attenuate catalepsy induced by D(2) receptor blockade. Here we examined the role of 5-HT(1A) receptor agonism in the reduced cataleptogenic potential of several novel antipsychotic agents in the crossed leg position (CLP) and the bar catalepsy tests in rats. When administered alone, ziprasidone produced marked catalepsy, whereas aripiprazole, bifeprunox, SLV313, SSR181507 and sarizotan did not. However, when 5-HT(1A) receptors were blocked with the selective antagonist, WAY100635 (0.63 mg/kg, SC), robust cataleptogenic properties of SLV313, bifeprunox and sarizotan were unmasked and the catalepsy induced by ziprasidone was accentuated. In contrast, only modest catalepsy was induced by aripiprazole and SSR181507, even following a higher dose of WAY100635 (2.5 mg/kg). This suggests that these compounds possess other anti-cataleptic properties, such as partial agonism at dopamine D(2) receptors. The capacity to reverse neuroleptic-induced catalepsy was investigated in interaction studies with haloperidol (2.5 mg/kg, SC). Whereas ziprasidone and aripiprazole did not markedly reduce the effects of haloperidol, SLV313 and sarizotan attenuated CLP catalepsy. In contrast, SSR181507 and bifeprunox potently inhibited both CLP and bar catalepsy. Taken together, these data show that 5-HT(1A) receptor activation reduces the cataleptogenic potential of novel antipsychotic agents but indicate marked diversity in the contribution of 5-HT(1A) and/or other mechanisms to the profiles of the drugs.

YiQiFuMai Powder Injection Attenuates Ischemia/Reperfusion-Induced Myocardial Apoptosis Through AMPK Activation.

PubMed

Li, Fang; Zheng, Xianjie; Fan, Xiaoxue; Zhai, Kefeng; Tan, Yisha; Kou, Junping; Yu, Boyang

2016-12-01

The YiQiFuMai powder injection (YQFM), a traditional Chinese medicine (TCM) prescription re-developed based on the well-known TCM formula Sheng-maisan, showed a wide range of pharmacological activities in cardiovascular diseases in clinics. However, its role in protection against myocardial ischemia/reperfusion (MI/R) injury has not been elucidated. The present study not only evaluated the cardioprotective effect of YQFM from MI/R injury but also investigated the potential molecular mechanisms both in vivo and in vitro. The myocardium infarct size, production of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac function, TUNEL staining, and caspase-3 activity were measured. Cell viability was determined, and cell apoptosis was measured by Hoechst 33342 staining and flow cytometry. Mitochondrial membrane potential (ΔΨm) was measured, and ATP content was quantified by bioluminescent assay. Expression of apoptosis-related proteins, including Caspase-3, Bcl-2, Bax, AMPKα, and phospho-AMPKα, was analyzed by western blotting. AMPKα siRNA transfection was also applied to the mechanism elucidation. YQFM at a concentration of 1.06 g/kg significantly reduced myocardium infarct size and the production of LDH, CK in serum, improved the cardiac function, and also produced a significant decrease of apoptotic index. Further, combined treatment with compound C partly attenuated the anti-apoptotic effect of YQFM. In addition, pretreatment with YQFM ranging from 25 to 400 μg/mL markedly improved cell viability and decreased LDH release. Moreover, YQFM inhibited H9c2 apoptosis, blocked the expression of caspase-3, and modulated Bcl-2 and Bax proteins, leading to an increased mitochondrial membrane potential and cellular ATP content. Mechanistically, YQFM activated AMP-activated protein kinase (AMPK) signaling pathways whereas pretreatment with AMPK inhibitor Compound C and application of transfection with AMPKα siRNA attenuated the anti-apoptotic effect of YQFM

A robust activity marking system for exploring active neuronal ensembles

PubMed Central

Sørensen, Andreas T; Cooper, Yonatan A; Baratta, Michael V; Weng, Feng-Ju; Zhang, Yuxiang; Ramamoorthi, Kartik; Fropf, Robin; LaVerriere, Emily; Xue, Jian; Young, Andrew; Schneider, Colleen; Gøtzsche, Casper René; Hemberg, Martin; Yin, Jerry CP; Maier, Steven F; Lin, Yingxi

2016-01-01

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system’s versatility. DOI: http://dx.doi.org/10.7554/eLife.13918.001 PMID:27661450

Investigation of the impact of snow removal activities on pavement markings in Virginia.

DOT National Transportation Integrated Search

1995-01-01

Snow removal activities resulted in substantial damage to pavement markings in Virginia over the last 2 years. Typically, the estimates of the extent of pavement marking damage are based on the observations of the staff of the Virginia Department of ...

[Limb remote ischemic preconditioning attenuates liver ischemia reperfusion injury by activating autophagy via modulating PPAR-γ pathway].

PubMed

Ruan, Wei; Liu, Qing; Chen, Chan; Li, Suobei; Xu, Junmei

2016-09-28

To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
 At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
 RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.

Simultaneous reconstruction of emission activity and attenuation coefficient distribution from TOF data, acquired with external transmission source

NASA Astrophysics Data System (ADS)

Panin, V. Y.; Aykac, M.; Casey, M. E.

2013-06-01

The simultaneous PET data reconstruction of emission activity and attenuation coefficient distribution is presented, where the attenuation image is constrained by exploiting an external transmission source. Data are acquired in time-of-flight (TOF) mode, allowing in principle for separation of emission and transmission data. Nevertheless, here all data are reconstructed at once, eliminating the need to trace the position of the transmission source in sinogram space. Contamination of emission data by the transmission source and vice versa is naturally modeled. Attenuated emission activity data also provide additional information about object attenuation coefficient values. The algorithm alternates between attenuation and emission activity image updates. We also proposed a method of estimation of spatial scatter distribution from the transmission source by incorporating knowledge about the expected range of attenuation map values. The reconstruction of experimental data from the Siemens mCT scanner suggests that simultaneous reconstruction improves attenuation map image quality, as compared to when data are separated. In the presented example, the attenuation map image noise was reduced and non-uniformity artifacts that occurred due to scatter estimation were suppressed. On the other hand, the use of transmission data stabilizes attenuation coefficient distribution reconstruction from TOF emission data alone. The example of improving emission images by refining a CT-based patient attenuation map is presented, revealing potential benefits of simultaneous CT and PET data reconstruction.

Maintaining vigorous activity attenuates 7-yr weight gain in 8340 runners.

PubMed

Williams, Paul T

2007-05-01

Body weight generally increases with aging in Western societies. Although training studies show that exercise produces acute weight loss, it is unclear whether the long-term maintenance of vigorous exercise attenuates the trajectory of age-related weight gain. Specifically, prior studies have not tested whether the maintenance of physical activity, in the absence of any change in activity, prevents weight gain. Prospective study of 6119 male and 2221 female runners whose running distances changed < 5 km x wk(-1) between baseline and follow-up surveys 7 yr later. On average, men who maintained modest (0-23 km x wk(-1)), intermediate (24-47 km x wk(-1)), or prolonged running distances (> or = 48 km x wk(-1)) all gained weight through age 64; however, those who maintained > or = 48 km x wk(-1) had one half the average annual weight gain of those who maintained < 24 km x wk(-1). For example, between the ages of 35 and 44 in men and 30 and 39 yr in women, those who maintained < 24 km x wk(-1) gained, on average, 2.1 and 2.9 kg more per decade than those averaging > 48 km x wk(-1). Age-related weight gain, and its attenuation by maintained exercise, were both greater in younger than in older men. Men's gains in waist circumference with age, and its attenuation by maintaining running, were the same in older and younger men. Regardless of age, women increased their body weight, waist circumference, and hip circumference over time, and these measurements were attenuated in proportion to their maintained running distance. In both sexes, running disproportionately prevented more extreme increases in weight. As they aged, men and women gained less weight in proportion to their levels of sustained vigorous activity. This long-term beneficial effect is in addition to the acute weight loss that occurs with increased activity.

FLZ Attenuates α-Synuclein-Induced Neurotoxicity by Activating Heat Shock Protein 70.

PubMed

Bao, Xiu-Qi; Wang, Xiao-Liang; Zhang, Dan

2017-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. The pathology of PD is caused by progressive degeneration of dopaminergic neurons and is characterized by the presence of intracellular inclusions known as Lewy bodies, composed mainly of α-synuclein. Heat shock proteins (HSPs) are crucial in protein quality control in cells. HSP70 in particular prevents the aggregation of protein aggregation, such as α-synuclein, providing a degree of protection against PD. The compound FLZ has been shown to protect several PD models in previous studies and was reported as an HSP inducer to protect against MPP + -induced neurotoxicity, but the mechanism remains unclear. In this study, we investigated the effects of FLZ-mediated HSP70 induction in α-synuclein transgenic mice and cells. FLZ treatment alleviated motor dysfunction and improved dopaminergic neuronal function in α-synuclein transgenic mice. HSP70 protein expression and transcriptional activity were increased by FLZ treatment, eliciting a reduction of α-synuclein aggregation and associated toxicity. The inhibition of HSP70 by quercetin or HSP70 siRNA markedly attenuated the neuroprotective effects of FLZ, confirming that FLZ exerted a neuroprotective effect through HSP70. We revealed that FLZ directly bound to and increased the expression of Hip, a cochaperone of HSP70, which in turn enhanced HSP70 activity. In conclusion, we defined a critical role for HSP70 and its cochaperones activated by FLZ in preventing neurodegeneration and proposed that targeting the HSP70 system may represent a potential therapy for α-synuclein-related diseases, such as PD.

Improving accuracy of simultaneously reconstructed activity and attenuation maps using deep learning.

PubMed

Hwang, Donghwi; Kim, Kyeong Yun; Kang, Seung Kwan; Seo, Seongho; Paeng, Jin Chul; Lee, Dong Soo; Lee, Jae Sung

2018-02-15

Simultaneous reconstruction of activity and attenuation using the maximum likelihood reconstruction of activity and attenuation (MLAA) augmented by time-of-flight (TOF) information is a promising method for positron emission tomography (PET) attenuation correction. However, it still suffers from several problems, including crosstalk artifacts, slow convergence speed, and noisy attenuation maps (μ-maps). In this work, we developed deep convolutional neural networks (CNNs) to overcome these MLAA limitations, and we verified their feasibility using a clinical brain PET data set. Methods: We applied the proposed method to one of the most challenging PET cases for simultaneous image reconstruction ( 18 F-FP-CIT PET scans with highly specific binding to striatum of the brain). Three different CNN architectures (convolutional autoencoder (CAE), U-net, hybrid of CAE and U-net) were designed and trained to learn x-ray computed tomography (CT) derived μ-map (μ-CT) from the MLAA-generated activity distribution and μ-map (μ-MLAA). PET/CT data of 40 patients with suspected Parkinson's disease were employed for five-fold cross-validation. For the training of CNNs, 800,000 transverse PET slices and CTs augmented from 32 patient data sets were used. The similarity to μ-CT of the CNN-generated μ-maps (μ-CAE, μ-Unet, and μ-Hybrid) and μ-MLAA was compared using Dice similarity coefficients. In addition, we compared the activity concentration of specific (striatum) and non-specific binding regions (cerebellum and occipital cortex) and the binding ratios in the striatum in the PET activity images reconstructed using those μ-maps. Results: The CNNs generated less noisy and more uniform μ-maps than original μ-MLAA. Moreover, the air cavities and bones were better resolved in the proposed CNN outputs. In addition, the proposed deep learning approach was useful for mitigating the crosstalk problem in the MLAA reconstruction. The hybrid network of CAE and U-net yielded the

77 FR 23490 - Agency Information Collection Activities: Country of Origin Marking Requirements for Containers...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... Activities: Country of Origin Marking Requirements for Containers or Holders AGENCY: U.S. Customs and Border... of Origin Marking Requirements for Containers or Holders. This is a proposed extension of an... Requirements for Containers or Holders. [[Page 23491

Attenuation of Activity in an Endogenous Analgesia Circuit by Ongoing Pain in the Rat

PubMed Central

Ferrari, Luiz F.; Gear, Robert W.; Levine, Jon D.

2010-01-01

Analgesic efficacy varies depending on the pain syndrome being treated. One reason for this may be a differential effect of individual pain syndromes on the function of endogenous pain control circuits at which these drugs act to produce analgesia. To test this hypothesis we examined the effects of diverse (i.e., ongoing inflammatory, neuropathic, or chronic widespread) pain syndromes on analgesia induced by activation of an opioid-mediated noxious stimulus-induced endogenous pain control circuit. This circuit was activated by subdermal capsaicin injection at a site remote from the site of nociceptive testing. Analgesia was not affected by carrageenan-induced inflammatory pain nor the early-phase of oxaliplatin neuropathy (a complication of cancer chemotherapy). However, the duration of analgesia was markedly shorter in the late-phase of oxaliplatin neuropathy and in alcoholic neuropathy. A model of fibromyalgia syndrome produced by chronic unpredictable stress and proinflammatory cytokines also shortened analgesia duration, but so did the same stress alone. Therefore, since chronic pain can activate neuroendocrine stress axes, we tested whether they are involved in the attenuation of analgesic duration induced by these pain syndromes. Rats in which the sympathoadrenal axis was ablated by adrenal medullectomy showed normal duration pain-induced analgesia in groups with either late-phase oxaliplatin neuropathy, alcoholic neuropathy, or exposure to sound stress. These results support the suggestion that pain syndromes can modulate activity in endogenous pain control circuits, and this effect is sympathoadrenal dependent. PMID:20943910

Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents.

PubMed

Lu, Yuyan; Guo, Haipeng; Sun, Yuxi; Pan, Xin; Dong, Jia; Gao, Di; Chen, Wei; Xu, Yawei; Xu, Dachun

2017-08-01

It has previously been demonstrated that the renin-angiotensin system is involved in the pathogenesis and development of pulmonary hypertension (PH). However, the efficacy of angiotensin II type I (AT1) receptor blockers in the treatment of PH is variable. The present study examined the effects of the AT1 receptor blocker valsartan on monocrotaline (MCT)‑induced PH in rats and chronic hypoxia‑induced PH in mice. The results demonstrated that valsartan markedly attenuated development of PH in rats and mice, as indicated by reduced right ventricular systolic pressure, diminished lung vascular remodeling and decreased right ventricular hypertrophy, compared with vehicle treated animals. Immunohistochemical analyses of proliferating cell nuclear antigen expression revealed that valsartan suppressed smooth muscle cell proliferation. Western blot analysis demonstrated that valsartan limited activation of p38, c‑Jun N‑terminal kinase 1/2 and extracellular signal‑regulated kinase 1/2 signaling pathways and significantly reduced MCT‑induced upregulation of pulmonary matrix metalloproteinases‑2 and ‑9, and transforming growth factor‑β1 expression. The results suggested that valsartan attenuates development of PH in rodents by reducing expression of extracellular matrix remodeling factors and limiting smooth muscle cell proliferation to decrease pathological vascular remodeling. Therefore, valsartan may be a valuable future therapeutic approach for the treatment of PH.

Productivity and cost of marking activities for single-tree selection and thinning treatments in Arkansas

Treesearch

Tymur Sydor; Richard A. Kluender; Rodney L. Busby; Matthew Pelkki

2004-01-01

An activity algorithm was developed for standard marking methods for natural pine stands in Arkansas. For the two types of marking methods examined, thinning (selection from below) and single-tree selection (selection from above), cycle time and cost models were developed. Basal area (BA) removed was the major influencing factor in both models. Marking method was...

77 FR 6815 - Agency Information Collection Activities: Country of Origin Marking Requirements for Containers...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Activities: Country of Origin Marking Requirements for Containers or Holders AGENCY: U.S. Customs and Border... information collection requirement concerning Country of Origin Marking Requirements for Containers or Holders... request for Office of Management and Budget (OMB) approval. All comments will become a matter of public...

NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex.

PubMed

Makeham, John M; Goodchild, Ann K; Pilowsky, Paul M

2005-06-01

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

Promoting physical activity at the pre-school playground: the effects of providing markings and play equipment.

PubMed

Cardon, Greet; Labarque, Valery; Smits, Dirk; De Bourdeaudhuij, Ilse

2009-04-01

We aimed to investigate the effects of providing play equipment and markings at the pre-school playground on physical activity engagement levels. We performed a cluster randomised control trial. In November and December 2007, a convenience sample of 40 public pre-schools in Flanders, Belgium, was randomly assigned to one of the following conditions: 1) in 10 pre-schools play equipment was provided, 2) in 10 pre-schools markings were painted on the playground, 3) in 10 schools play equipment was provided and markings were painted, 4) 10 schools served as a control condition. Accelerometer-based physical activity levels during recess were evaluated at baseline and 4 to 6 weeks after the implementation of the intervention in 583 children (52% boys; mean age 5.3 years, SD 0.4). At baseline pre-schoolers spent only 11.2% (average: 4.7 min) of recess time in moderate to vigorous activity, while 61.3% (average: 25.7 min) was spent in sedentary activity. The interventions were not effective in increasing the average activity levels or the percentages of engagement in moderate or vigorous activity, or in decreasing sedentary time. Providing playground markings or play equipment is not sufficient to increase activity levels and decrease levels of sedentary activity during pre-school recess. More activating supervision and the inclusion of more structured physical activity seem needed.

Brazilian Red Propolis Attenuates Inflammatory Signaling Cascade in LPS-Activated Macrophages

PubMed Central

Bueno-Silva, Bruno; Kawamoto, Dione; Ando-Suguimoto, Ellen S.; Alencar, Severino M.; Rosalen, Pedro L.; Mayer, Marcia P. A.

2015-01-01

Although previous studies suggested an anti-inflammatory property of Brazilian red propolis (BRP), the mechanisms involved in the anti-inflammatory effects of BRP and its activity on macrophages were still not elucidated. This study aimed to evaluate whether BRP attenuates the inflammatory effect of LPS on macrophages and to investigate its underlying mechanisms. BRP was added to RAW 264.7 murine macrophages after activation with LPS. NO production, cell viability, cytokines profile were evaluated. Activation of inflammatory signaling pathways and macrophage polarization were determined by RT-qPCR and Western blot. BRP at 50 μg/ml inhibited NO production by 78% without affecting cell viability. Cd80 and Cd86 were upregulated whereas mrc1 was down regulated by BRP indicating macrophage polarization at M1. BRP attenuated the production of pro-inflammatory mediators IL-12, GM-CSF, IFN-Ɣ, IL-1β in cell supernatants although levels of TNF- α and IL-6 were slightly increased after BRP treatment. Levels of IL-4, IL-10 and TGF-β were also reduced by BRP. BRP significantly reduced the up-regulation promoted by LPS of transcription of genes in inflammatory signaling (Pdk1, Pak1, Nfkb1, Mtcp1, Gsk3b, Fos and Elk1) and of Il1β and Il1f9 (fold-change rate > 5), which were further confirmed by the inhibition of NF-κB and MAPK signaling pathways. Furthermore, the upstream adaptor MyD88 adaptor-like (Mal), also known as TIRAP, involved in TLR2 and TLR4 signaling, was down- regulated in BRP treated LPS-activated macrophages. Given that BRP inhibited multiple signaling pathways in macrophages involved in the inflammatory process activated by LPS, our data indicated that BRP is a noteworthy food-source for the discovery of new bioactive compounds and a potential candidate to attenuate exhacerbated inflammatory diseases. PMID:26660901

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

PubMed

Suganuma, Eisuke; Niimura, Fumio; Matsuda, Shinichi; Ukawa, Toshiko; Nakamura, Hideaki; Sekine, Kaori; Kato, Masahiko; Aiba, Yuji; Koga, Yasuhiro; Hayashi, Kuniyoshi; Takahashi, Osamu; Mochizuki, Hiroyuki

2017-04-01

Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease. Five-wk-old C57/BL6J male mice were intraperitoneally injected with Lactobacillus casei cell wall extract to induce coronary inflammation and divided into four groups: placebo, intravenous immunoglobulin (IVIG), losartan, and IVIG+losartan. After 2 wk, mice were harvested. The coronary perivasculitis was significantly attenuated by losartan but not by IVIG alone, and further dramatic attenuation by IVIG+losartan was observed. The frequency of Lactobacillus casei cell wall extract-induced myocarditis (80%) was markedly lowered by losartan (22%) and IVIG+losartan (0%). Furthermore, interleukin (IL)-6 mRNA was markedly attenuated by IVIG+losartan. Serum levels of IL-6, TNF-α, MCP-1, and IL-10 after Lactobacillus casei cell wall extract injection were slightly decreased by IVIG or losartan. Moreover, IL-1β, IL-10, and MCP-1 levels were significantly decreased by IVIG+losartan. The addition of losartan to IVIG strongly attenuated the severity of coronary perivasculitis and the incidence of myocarditis, along with suppressing systemic/local cytokines as well as the activated macrophage infiltration. Therefore, losartan may be a potentially useful additive drug for the acute phase of Kawasaki disease to minimize coronary artery lesions.

The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice.

PubMed

Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

2016-01-01

Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis.

The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice

PubMed Central

Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

2016-01-01

Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis. PMID:27186319

Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.

PubMed

Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng

2016-09-01

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity

PubMed Central

Komori, Hideyuki; Xiao, Qi; McCartney, Brooke M.; Lee, Cheng-Yu

2014-01-01

During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood. Here, we report that Brat specifies INP identity through its N-terminal B-boxes via a novel mechanism that is independent of asymmetric protein segregation. Brat-mediated specification of INP identity is critically dependent on the function of the Wnt destruction complex, which attenuates the activity of β-catenin/Armadillo (Arm) in immature INPs. Aberrantly increasing Arm activity in immature INPs further exacerbates the defects in the specification of INP identity and enhances the supernumerary neuroblast mutant phenotype in brat mutant brains. By contrast, reducing Arm activity in immature INPs suppresses supernumerary neuroblast formation in brat mutant brains. Finally, reducing Arm activity also strongly suppresses supernumerary neuroblasts induced by overexpression of klu. Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification. PMID:24257623

Active vibration attenuating seat suspension for an armored helicopter crew seat

NASA Astrophysics Data System (ADS)

Sztein, Pablo Javier

An Active Vibration Attenuating Seat Suspension (AVASS) for an MH-60S helicopter crew seat is designed to protect the occupants from harmful whole-body vibration (WBV). Magnetorheological (MR) suspension units are designed, fabricated and installed in a helicopter crew seat. These MR isolators are built to work in series with existing Variable Load Energy Absorbers (VLEAs), have minimal increase in weight, and maintain crashworthiness for the seat system. Refinements are discussed, based on testing, to minimize friction observed in the system. These refinements include the addition of roller bearings to replace friction bearings in the existing seat. Additionally, semi-active control of the MR dampers is achieved using special purpose built custom electronics integrated into the seat system. Experimental testing shows that an MH-60S retrofitted with AVASS provides up to 70.65% more vibration attenuation than the existing seat configuration as well as up to 81.1% reduction in vibration from the floor.

Unbiased Proteomics of Early Lewy Body Formation Model Implicates Active Microtubule Affinity-Regulating Kinases (MARKs) in Synucleinopathies

PubMed Central

Riddle, Dawn M.; Zhang, Bin

2017-01-01

Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation. Activated MARK proteins (MARKs) accumulated in LB-like inclusions in this cell-based model as well as in a mouse model of LB disease and in LBs of postmortem synucleinopathy brains. Inhibition of MARKs dramatically exacerbated α-synuclein pathology. These findings implicate MARKs early in synucleinopathy pathogenesis and as potential therapeutic drug targets. SIGNIFICANCE STATEMENT Neurodegenerative diseases are diagnosed definitively only in postmortem brains by the presence of key misfolded and aggregated disease proteins, but cellular processes leading to accumulation of these proteins have not been well elucidated. Parkinson's disease (PD) patients accumulate misfolded α-synuclein in LBs, the diagnostic signatures of PD. Here, unbiased mass spectrometry was used to identify the microtubule affinity-regulating kinase family (MARKs) as activated and insoluble in a neuronal culture PD model. Aberrant activation of MARKs was also found in a PD mouse model and in postmortem PD brains. Further, inhibition of MARKs led to increased pathological α-synuclein burden. We conclude that MARKs play a role in PD pathogenesis. PMID:28522732

Activation of Neurotensin Receptor Type 1 Attenuates Locomotor Activity

PubMed Central

Vadnie, Chelsea A.; Hinton, David J.; Choi, Sun; Choi, YuBin; Ruby, Christina L.; Oliveros, Alfredo; Prieto, Miguel L.; Park, Jun Hyun; Choi, Doo-Sup

2014-01-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

Naringin Attenuates Cerebral Ischemia-Reperfusion Injury Through Inhibiting Peroxynitrite-Mediated Mitophagy Activation.

PubMed

Feng, Jinghan; Chen, Xingmiao; Lu, Shengwen; Li, Wenting; Yang, Dan; Su, Weiwei; Wang, Xijun; Shen, Jiangang

2018-04-07

Excessive autophagy/mitophagy plays important roles during cerebral ischemia-reperfusion (I/R) injury. Peroxynitrite (ONOO - ), a representative reactive nitrogen species, mediates excessive mitophagy activation and exacerbates cerebral I/R injury. In the present study, we tested the hypothesis that naringin, a natural antioxidant, could inhibit ONOO - -mediated mitophagy activation and attenuate cerebral I/R injury. Firstly, we demonstrated that naringin possessed strong ONOO - scavenging capability and also inhibited the production of superoxide and nitric oxide in SH-SY5Y cells exposed to 10 h oxygen-glucose-deprivation plus 14 h of reoxygenation or ONOO - donor 3-morpholinosydnonimine conditions. Naringin also inhibited the expression of NADPH oxidase subunits and iNOS in rat brains subjected to 2 h ischemia plus 22 h reperfusion. Next, we found that naringin was able to cross the blood-brain barrier, and naringin decreased neurological deficit score, reduced infarct size, and attenuated apoptotic cell death in the ischemia-reperfused rat brains. Furthermore, naringin reduced 3-nitrotyrosine formation, decreased the ratio of LC3-II to LC3-I in mitochondrial fraction, and inhibited the translocation of Parkin to the mitochondria. Taken together, naringin could be a potential therapeutic agent to prevent the brain from I/R injury via attenuating ONOO - -mediated excessive mitophagy.

Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.

PubMed

Batman, Angela M; Munzar, Patrik; Beardsley, Patrick M

2005-05-01

Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice. Adult male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily (Monday-Friday) 15-min experimental sessions. After characterizing a dose-response curve for nicotine, we tested the ability of the 5HT(2A/2C) agonists (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1-1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0 mg/kg), and the 5HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.01 mg/kg-1.0 mg/kg) to modulate nicotine's discriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine's effects on locomotor activity in mice. The 5HT2A/2C agonists-in particular DOI-dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly suppressing responding. DOI also dose dependently blocked nicotine's acute rate-lowering locomotor activity effects. These results indicate that activation of serotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine.

Marked point process for modelling seismic activity (case study in Sumatra and Java)

NASA Astrophysics Data System (ADS)

Pratiwi, Hasih; Sulistya Rini, Lia; Wayan Mangku, I.

2018-05-01

Earthquake is a natural phenomenon that is random, irregular in space and time. Until now the forecast of earthquake occurrence at a location is still difficult to be estimated so that the development of earthquake forecast methodology is still carried out both from seismology aspect and stochastic aspect. To explain the random nature phenomena, both in space and time, a point process approach can be used. There are two types of point processes: temporal point process and spatial point process. The temporal point process relates to events observed over time as a sequence of time, whereas the spatial point process describes the location of objects in two or three dimensional spaces. The points on the point process can be labelled with additional information called marks. A marked point process can be considered as a pair (x, m) where x is the point of location and m is the mark attached to the point of that location. This study aims to model marked point process indexed by time on earthquake data in Sumatra Island and Java Island. This model can be used to analyse seismic activity through its intensity function by considering the history process up to time before t. Based on data obtained from U.S. Geological Survey from 1973 to 2017 with magnitude threshold 5, we obtained maximum likelihood estimate for parameters of the intensity function. The estimation of model parameters shows that the seismic activity in Sumatra Island is greater than Java Island.

Intermittent fasting attenuates inflammasome activity in ischemic stroke.

PubMed

Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

2014-07-01

Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

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

Guo, Shiguang; Mao, Li; Ji, Feng, E-mail: huaiaifengjidr@163.com

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the othermore » hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.« less

Activation of neurotensin receptor type 1 attenuates locomotor activity.

PubMed

Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup

2014-10-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2

PubMed Central

Tian, Yue; Wu, Xiuying; Guo, Shanbin; Ma, Ling; Huang, Wei; Zhao, Xiaochun

2017-01-01

Minocycline has been demonstrated to exert neuroprotective effects in various experimental models. In the present study, we investigated the mechanisms underlying the protective effects of minocycline on cell injury induced by the inhalation of the anesthetic, sevoflurane. In our in vivo experiments using rats, minocycline attenuated sevoflurane-induced neuronal degeneration and apoptosis in the rat hippocampus, and this effect was associated with the minocycline-mediated suppression of oxidative stress in the hippocampus. In in vitro experiments, minocycline inhibited sevoflurane-induced apoptosis and the production of reactive oxygen species (ROS) in H4 human neuroglioma cells. In addition, minocycline suppressed the sevoflurane-induced upregulation of interleukin (IL)-6 and the activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells. Furthermore, we found that nuclear factor E2-related factor 2 (Nrf2), an activator of the stress response, was upregulated and activated upon sevoflurane treatment both in the rat hippocampus and in H4 cells. In addition, minocycline further augmented the upregulation and activation of Nrf2 when used in conjunction with sevoflurane. Moreover, the knockdown of Nrf2 in H4 cells by small interfering RNA (siRNA) diminished the cytoprotective effect of minocycline, and attenuated the inhibitory effect of minocycline on ROS production, IL-6 upregulation and the activation of the NF-κB signaling pathway. On the whole, our findings indicate that minocycline may exert protective effects against sevoflurane-induced cell injury via the Nrf2-modulated antioxidant response and the inhibition of the activation of the NF-κB signaling pathway. PMID:28260081

Colonic Marking With Near-Infrared, Light-Emitting, Diode-Activated Indocyanine Green for Laparoscopic Colorectal Surgery.

PubMed

Nagata, Jun; Fukunaga, Yosuke; Akiyoshi, Takashi; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Yamamoto, Noriko; Ueno, Masashi

2016-02-01

Accurate identification of the location of colorectal lesions is crucial during laparoscopic surgery. Endoscopic marking has been used as an effective preoperative marker for tumor identification. We investigated the feasibility and safety of an imaging method using near-infrared, light-emitting, diode-activated indocyanine green fluorescence in colorectal laparoscopic surgery. This was a single-institution, prospective study. This study was conducted in a tertiary referral hospital. We enrolled 24 patients who underwent laparoscopic surgery. Indocyanine green and India ink were injected into the same patients undergoing preoperative colonoscopy for colon cancer. During subsequent laparoscopic resection of colorectal tumors, the colon was first observed with white light. Then, indocyanine green was activated with a light-emitting diode at 760 nm as the light source. Near-infrared-induced fluorescence showed tumor location clearly and accurately in all 24 of the patients. All of the patients who underwent laparoscopic surgery after marking had positive indocyanine green staining at the time of surgery. Perioperative complications attributed to dye use were not observed. This study is limited by the cost of indocyanine green detection, the timing of the colonoscopy and tattooing in relation to the operation and identification with indocyanine green, and the small size of the series. These data suggest that our novel method for colonic marking with fluorescence imaging of near-infrared, light-emitting, diode-activated indocyanine green is feasible and safe. This method is useful, has no adverse effects, and can be used for perioperative identification of tumor location. Near-infrared, light-emitting, diode-activated indocyanine green has potential use as a colonic marking agent.

Pseudolaric acid B attenuates atherosclerosis progression and inflammation by suppressing PPARγ-mediated NF-κB activation.

PubMed

Li, Tan; Wang, Wei; Li, Yu-Xiu; Li, Xiao; Ji, Wen-Jie; Ma, Yong-Qiang; Chen, Hong; Zhao, Ji-Hong; Zhou, Xin

2018-06-01

Atherosclerosis is a progressive disease of large arteries characterized with chronic inflammation and aberrant immune response. Pseudolaric acid B (PB) has been found to exert multiple effects by inhibiting inflammatory response. However, there is no comprehensive assessment of the effects of PB on atherosclerosis using relevant in vivo and in vitro models. Male ApoE -/- mice were treated with PB orally with a high fat diet (HFD) to clarify its anti-atherosclerotic activities. RAW264.7 macrophage line, a well-accepted cell model of atherosclerosis, was used to investigate anti-inflammatory effects and molecular mechanisms of PB. PB significantly attenuated atherosclerotic lesions by modulating plasma lipid profiles as well as inhibiting inflammatory responses in macrophages of atherosclerotic mice. Meanwhile, PB markedly suppressed the expression of pro-inflammatory cytokines, and regulated cholesterol efflux related genes in oxidative low density lipoprotein (ox-LDL)-loaded macrophages. The cellular uptake of Dil-labeled ox-LDL was significantly inhibited by PB either. Moreover, the ability of PB to suppress nuclear factor kappa B (NF-κB) and activate peroxisome proliferator-activated receptor gamma (PPARγ) was confirmed using luciferase reporter assays. Conversely, the selective PPARγ antagonist GW9662 reversed the influence of PB in macrophages. Together, these findings indicate that PB exerts its protective effects on atherosclerosis by inhibiting macrophage-mediated inflammatory response and cellular ox-LDL uptake, and promoting cholesterol efflux by suppressing NF-κB activation PPARγ-dependently. Therefore, PB may be a promising agent for inflammatory and atherosclerotic diseases. Copyright © 2018. Published by Elsevier B.V.

Clusterless Decoding of Position From Multiunit Activity Using A Marked Point Process Filter

PubMed Central

Deng, Xinyi; Liu, Daniel F.; Kay, Kenneth; Frank, Loren M.; Eden, Uri T.

2016-01-01

Point process filters have been applied successfully to decode neural signals and track neural dynamics. Traditionally, these methods assume that multiunit spiking activity has already been correctly spike-sorted. As a result, these methods are not appropriate for situations where sorting cannot be performed with high precision such as real-time decoding for brain-computer interfaces. As the unsupervised spike-sorting problem remains unsolved, we took an alternative approach that takes advantage of recent insights about clusterless decoding. Here we present a new point process decoding algorithm that does not require multiunit signals to be sorted into individual units. We use the theory of marked point processes to construct a function that characterizes the relationship between a covariate of interest (in this case, the location of a rat on a track) and features of the spike waveforms. In our example, we use tetrode recordings, and the marks represent a four-dimensional vector of the maximum amplitudes of the spike waveform on each of the four electrodes. In general, the marks may represent any features of the spike waveform. We then use Bayes’ rule to estimate spatial location from hippocampal neural activity. We validate our approach with a simulation study and with experimental data recorded in the hippocampus of a rat moving through a linear environment. Our decoding algorithm accurately reconstructs the rat’s position from unsorted multiunit spiking activity. We then compare the quality of our decoding algorithm to that of a traditional spike-sorting and decoding algorithm. Our analyses show that the proposed decoding algorithm performs equivalently or better than algorithms based on sorted single-unit activity. These results provide a path toward accurate real-time decoding of spiking patterns that could be used to carry out content-specific manipulations of population activity in hippocampus or elsewhere in the brain. PMID:25973549

Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

PubMed

Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

2016-12-15

Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression. Copyright © 2016. Published by Elsevier B.V.

Helping behavior induced by empathic concern attenuates anterior cingulate activation in response to others' distress.

PubMed

Kawamichi, Hiroaki; Yoshihara, Kazufumi; Sugawara, Sho K; Matsunaga, Masahiro; Makita, Kai; Hamano, Yuki H; Tanabe, Hiroki C; Sadato, Norihiro

2016-01-01

Helping behavior is motivated by empathic concern for others in distress. Although empathic concern is pervasive in daily life, its neural mechanisms remain unclear. Empathic concern involves the suppression of the emotional response to others' distress, which occurs when individuals distance themselves emotionally from the distressed individual. We hypothesized that helping behavior induced by empathic concern, accompanied by perspective-taking, would attenuate the neural activation representing aversive feelings. We also predicted reward system activation due to the positive feeling resulting from helping behavior. Participant underwent functional magnetic resonance imaging while playing a virtual ball-toss game. In some blocks ("concern condition"), one player ("isolated player") did not receive ball-tosses from other players. In this condition, participants increased ball-tosses to the isolated player (helping behavior). Participants then evaluated the improved enjoyment of the isolated player resulting from their helping behavior. Anterior cingulate activation during the concern condition was attenuated by the evaluation of the effect of helping behavior. The right temporoparietal junction, which is involved in perspective-taking and the dorsal striatum, part of the reward system, were also activated during the concern condition. These results suggest that humans can attenuate affective arousal by anticipating the positive outcome of empathic concern through perspective-taking.

PET attenuation correction for rigid MR Tx/Rx coils from 176Lu background activity

NASA Astrophysics Data System (ADS)

Lerche, Christoph W.; Kaltsas, Theodoris; Caldeira, Liliana; Scheins, Jürgen; Rota Kops, Elena; Tellmann, Lutz; Pietrzyk, Uwe; Herzog, Hans; Shah, N. Jon

2018-02-01

One challenge for PET-MR hybrid imaging is the correction for attenuation of the 511 keV annihilation radiation by the required RF transmit and/or RF receive coils. Although there are strategies for building PET transparent Tx/Rx coils, such optimised coils still cause significant attenuation of the annihilation radiation leading to artefacts and biases in the reconstructed activity concentrations. We present a straightforward method to measure the attenuation of Tx/Rx coils in simultaneous MR-PET imaging based on the natural 176Lu background contained in the scintillator of the PET detector without the requirement of an external CT scanner or PET scanner with transmission source. The method was evaluated on a prototype 3T MR-BrainPET produced by Siemens Healthcare GmbH, both with phantom studies and with true emission images from patient/volunteer examinations. Furthermore, the count rate stability of the PET scanner and the x-ray properties of the Tx/Rx head coil were investigated. Even without energy extrapolation from the two dominant γ energies of 176Lu to 511 keV, the presented method for attenuation correction, based on the measurement of 176Lu background attenuation, shows slightly better performance than the coil attenuation correction currently used. The coil attenuation correction currently used is based on an external transmission scan with rotating 68Ge sources acquired on a Siemens ECAT HR  +  PET scanner. However, the main advantage of the presented approach is its straightforwardness and ready availability without the need for additional accessories.

Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

PubMed

Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

2015-01-01

It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

Attenuation and Restoration of Severe Acute Respiratory Syndrome Coronavirus Mutant Lacking 2′-O-Methyltransferase Activity

PubMed Central

Menachery, Vineet D.; Yount, Boyd L.; Josset, Laurence; Gralinski, Lisa E.; Scobey, Trevor; Agnihothram, Sudhakar; Katze, Michael G.

2014-01-01

ABSTRACT The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern respiratory syndrome CoV (MERS-CoV) underscores the importance of understanding critical aspects of CoV infection and pathogenesis. Despite significant insights into CoV cross-species transmission, replication, and virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification of SARS-CoV NSP16 as a viral 2′-O-methyltransferase (2′-O-MTase) led to the possibility of utilizing this pathway to both attenuate SARS-CoV infection and develop novel therapeutic treatment options. Mutations were introduced into SARS-CoV NSP16 within the conserved KDKE motif and effectively attenuated the resulting SARS-CoV mutant viruses both in vitro and in vivo. While viruses lacking 2′-O-MTase activity had enhanced sensitivity to type I interferon (IFN), they were not completely restored in their absence in vivo. However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2′-O RNA, resulted in restored replication and virulence of the dNSP16 mutant virus. Finally, using the mutant as a live-attenuated vaccine showed significant promise for possible therapeutic development against SARS-CoV. Together, the data underscore the necessity of 2′-O-MTase activity for SARS-CoV pathogenesis and identify host immune pathways that mediate this attenuation. In addition, we describe novel treatment avenues that exploit this pathway and could potentially be used against a diverse range of viral pathogens that utilize 2′-O-MTase activity to subvert the immune system. IMPORTANCE Preventing recognition by the host immune response represents a critical aspect necessary for successful viral infection. Several viruses, including SARS-CoV, utilize virally encoded 2′-O-MTases to camouflage and obscure their viral RNA from host cell sensing machinery, thus preventing recognition and

Attenuation of radionuclide activity by metal-cup arthroplasties

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

Rosenthall, L.; Rosenthall, S.

1985-04-01

The half-value layers of stainless steel, bone cement, and polyethylene were measured for /sup 99m/Tc, /sup 67/Ga, /sup 111/In, and /sup 201/TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in /sup 99m/Tc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. /sup 67/Ga, using the 184 and 300 keV peaks, and /sup 111/In have greater half-value layers than /sup 99m/Tc and are subject to less attenuation bymore » the metallic cup.« less

INDIRECT MEASUREMENT OF BIOLOGICAL ACTIVITY TO MONITOR NATURAL ATTENUATION

EPA Science Inventory

The remediation of ground water contamination by natural attenuation, specifically biodegradation, requires continual monitoring. This research is aimed at improving methods for evaluating the long-term performance of Monitored Natural Attenuation (MNA), specifically changes in ...

USP21 regulates Hippo pathway activity by mediating MARK protein turnover.

PubMed

Nguyen, Hung Thanh; Kugler, Jan-Michael; Loya, Anand C; Cohen, Stephen M

2017-09-08

The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components and deubiquitylating enzymes that counteract these ubiquitin ligases have been implicated in human cancer. Here we identify the USP21 deubiquitylating enzyme as a novel regulator of Hippo pathway activity. We provide evidence that USP21 regulates YAP/TAZ activity by controlling the stability of MARK kinases, which promote Hippo signaling. Low expression of USP21 in early stage renal clear cell carcinoma suggests that USP21 may be a useful biomarker.

Royal jelly attenuates azathioprine induced toxicity in rats.

PubMed

Ahmed, Walaa M S; Khalaf, A A; Moselhy, Walaa A; Safwat, Ghada M

2014-01-01

In the present study, we investigated the potential protective effects of royal jelly against azathioprine-induced toxicity in rat. Intraperitoneal administration of azathioprine (50 mg/kgB.W.) induced a significant decrease in RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by marked pathological changes in the liver. Oral administration of royal jelly (200 mg/kgB.W.) was efficient in counteracting azathioprine toxicity whereas it altered the anemic condition, leucopenia and thrombocytopenia induced by azathioprine. Furthermore, royal jelly exerted significant protection against liver damage induced by azathioprine through reduction of the elevated activities of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly possesses a capability to attenuate azathioprine-induced toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

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

Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032; Zhu, Bo

2014-01-03

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid andmore » glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.« less

Active marks structure optimization for optical-electronic systems of spatial position control of industrial objects

NASA Astrophysics Data System (ADS)

Sycheva, Elena A.; Vasilev, Aleksandr S.; Lashmanov, Oleg U.; Korotaev, Valery V.

2017-06-01

The article is devoted to the optimization of optoelectronic systems of the spatial position of objects. Probabilistic characteristics of the detection of an active structured mark on a random noisy background are investigated. The developed computer model and the results of the study allow us to estimate the probabilistic characteristics of detection of a complex structured mark on a random gradient background, and estimate the error of spatial coordinates. The results of the study make it possible to improve the accuracy of measuring the coordinates of the object. Based on the research recommendations are given on the choice of parameters of the optimal mark structure for use in opticalelectronic systems for monitoring the spatial position of large-sized structures.

Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.

PubMed

Chao, Dongman; Bazzy-Asaad, Alia; Balboni, Gianfranco; Salvadori, Severo; Xia, Ying

2008-09-01

We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.

The effect of metal artefact reduction on CT-based attenuation correction for PET imaging in the vicinity of metallic hip implants: a phantom study.

PubMed

Harnish, Roy; Prevrhal, Sven; Alavi, Abass; Zaidi, Habib; Lang, Thomas F

2014-07-01

To determine if metal artefact reduction (MAR) combined with a priori knowledge of prosthesis material composition can be applied to obtain CT-based attenuation maps with sufficient accuracy for quantitative assessment of (18)F-fluorodeoxyglucose uptake in lesions near metallic prostheses. A custom hip prosthesis phantom with a lesion-sized cavity filled with 0.2 ml (18)F-FDG solution having an activity of 3.367 MBq adjacent to a prosthesis bore was imaged twice with a chrome-cobalt steel hip prosthesis and a plastic replica, respectively. Scanning was performed on a clinical hybrid PET/CT system equipped with an additional external (137)Cs transmission source. PET emission images were reconstructed from both phantom configurations with CT-based attenuation correction (CTAC) and with CT-based attenuation correction using MAR (MARCTAC). To compare results with the attenuation-correction method extant prior to the advent of PET/CT, we also carried out attenuation correction with (137)Cs transmission-based attenuation correction (TXAC). CTAC and MARCTAC images were scaled to attenuation coefficients at 511 keV using a trilinear function that mapped the highest CT values to the prosthesis alloy attenuation coefficient. Accuracy and spatial distribution of the lesion activity was compared between the three reconstruction schemes. Compared to the reference activity of 3.37 MBq, the estimated activity quantified from the PET image corrected by TXAC was 3.41 MBq. The activity estimated from PET images corrected by MARCTAC was similar in accuracy at 3.32 MBq. CTAC corrected PET images resulted in nearly 40 % overestimation of lesion activity at 4.70 MBq. Comparison of PET images obtained with the plastic and metal prostheses in place showed that CTAC resulted in a marked distortion of the (18)F-FDG distribution within the lesion, whereas application of MARCTAC and TXAC resulted in lesion distributions similar to those observed with the plastic replica. MAR combined

Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

PubMed

Chen, Meng-Chuan; Chen, Yen-Lin; Lee, Chi-Feng; Hung, Chih-Huang; Chou, Tz-Chong

2015-01-01

Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M) extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1

PubMed Central

Chen, Meng-Chuan; Chen, Yen-Lin; Lee, Chi-Feng; Hung, Chih-Huang; Chou, Tz-Chong

2015-01-01

Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M) extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis. PMID:26600425

Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

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

Hsu, Ya-Yun; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Tseng, Yu-Ting

Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treatedmore » cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation

PubMed Central

Shao, Jiaxiang; Liu, Tengyuan; Xie, Qian Reuben; Zhang, Tingting; Yu, Hemei; Wang, Boshi; Ying, Weihai; Mruk, Dolores D.; Silvestrini, Bruno; Cheng, C. Yan; Xia, Weiliang

2014-01-01

Neuroinflammation caused by microglial activation plays a key role in ischemia, neurodegeneration and many other CNS diseases. In this study, we found that Adjudin, a potential non-hormonal male contraceptive, exhibits additional function to reduce the production of proinflammatory mediators. Adjudin significantly inhibited LPS-induced IL-6 release and IL-6, IL-1β, TNF-α expression in BV2 microglial cells. Furthermore, Adjudin exhibited anti-inflammatory properties by suppression of NF-κB p65 nuclear translocation and DNA binding activity as well as ERK MAPK phosphorylation. To determine the in vivo effect of Adjudin, we used a permanent middle cerebral artery occlusion (pMCAO) mouse model and found that Adjudin could reduce ischemia-induced CD11b expression, a marker of microglial activation. Furthermore, Adjudin treatment attenuated brain edema and neurological deficits after ischemia but did not reduce infarct volume. Thus, our data suggest that Adjudin may be useful for mitigating neuroinflammation. PMID:23084372

Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

PubMed

Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

2018-06-01

Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding.

PubMed

Boeke, Emily A; Moscarello, Justin M; LeDoux, Joseph E; Phelps, Elizabeth A; Hartley, Catherine A

2017-05-03

Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses. SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and

Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding

PubMed Central

Boeke, Emily A.; Moscarello, Justin M.; Phelps, Elizabeth A.

2017-01-01

Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses. SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and

Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

PubMed

Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

2017-03-06

The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A novel inhibitor of active protein kinase G attenuates chronic inflammatory and osteoarthritic pain.

PubMed

Sung, Ying-Ju; Sofoluke, Nelson; Nkamany, Mary; Deng, Shixian; Xie, Yuli; Greenwood, Jeremy; Farid, Ramy; Landry, Donald W; Ambron, Richard T

2017-05-01

Activating PKG-1α induces a long-term hyperexcitability (LTH) in nociceptive neurons. Since the LTH correlates directly with chronic pain in many animal models, we tested the hypothesis that inhibiting PKG-1α would attenuate LTH-mediated pain. We first synthesized and characterized compound N46 (N-((3R,4R)-4-(4-(2-fluoro-3-methoxy-6-propoxybenzoyl)benzamido)pyrrolidin-3-yl)-1H-indazole-5-carboxamide). N46 inhibits PKG-1α with an IC50 of 7.5 nmol, was highly selective when tested against a panel of 274 kinases, and tissue distribution studies indicate that it does not enter the CNS. To evaluate its antinociceptive potential, we used 2 animal models in which the pain involves both activated PKG-1α and LTH. Injecting complete Freund's adjuvant (CFA) into the rat hind paw causes a thermal hyperalgesia that was significantly attenuated 24 hours after a single intravenous injection of N46. Next, we used a rat model of osteoarthritic knee joint pain and found that a single intra-articular injection of N46 alleviated the pain 14 days after the pain was established and the relief lasted for 7 days. Thermal hyperalgesia and osteoarthritic pain are also associated with the activation of the capsaicin-activated transient receptor protein vanilloid-1 (TRPV1) channel. We show that capsaicin activates PKG-1α in nerves and that a subcutaneous delivery of N46 attenuated the mechanical and thermal hypersensitivity elicited by exposure to capsaicin. Thus, PKG-1α appears to be downstream of the transient receptor protein vanilloid-1. Our studies provide proof of concept in animal models that a PKG-1α antagonist has a powerful antinociceptive effect on persistent, already existing inflammatory pain. They further suggest that N46 is a valid chemotype for the further development of such antagonists.

IMPLEMENTATION OF NATURAL ATTENUATION AT A JP-4 JET FUEL RELEASE AFTER ACTIVE REMEDIATION

EPA Science Inventory

After eighteen months of active remediation at a JP-4 jet-fuel spill, a residual of unremediated hydrocarbon remained. Further site characterization was conducted to evaluate the contribution of natural attenuation to control exposure to hazards associated with the residual cont...

Ulinastatin post-treatment attenuates lipopolysaccharide-induced acute lung injury in rats and human alveolar epithelial cells

PubMed Central

Luo, Yunpeng; Che, Wen; Zhao, Mingyan

2017-01-01

Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced acute lung injury (ALI). High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of ALI. The aim of this study was to investigate whether UTI attenuates ALI through the inhibition of HMGB1 expression and to elucidate the underlying molecular mechanisms. ALI was induced in male rats by the intratracheal instillation of LPS (5 mg/kg). UTI was administered intraperitoneally 30 min following exposure to LPS. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of UTI. An enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blot analysis was performed to detect the changes in the expression levels of Toll-like receptor 2/4 (TLR2/4) and the activation of nuclear factor-κB (NF-κB). The results revealed that UTI significantly protected the animals from LPS-induced ALI, as evidenced by the decrease in the lung wet to dry weight ratio, total cells, neutrophils, macrophages and myeloperoxidase activity, associated with reduced lung histological damage. We also found that UTI post-treatment markedly inhibited the release of HMGB1 and other pro-inflammatory cytokines. Furthermore, UTI significantly inhibited the LPS-induced increase in TLR2/4 protein expression and NF-κB activation in lung tissues. In vitro, UTI markedly inhibited the expression of TLR2/4 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. The findings of our study indicate that UTI attenuates LPS-induced ALI through the inhibition of HMGB1 expression in rats. These benefits are associated with the inhibition of the activation of the TLR2/4-NF-κB pathway by UTI. PMID:27959396

The way to a man's heart is through his stomach: much 'diaphragmatic' attenuation is likely gastric, and effervescent granules enhance cardiac imaging.

PubMed

Munn, Samson

2004-12-01

Avoidance of falsely positive results depends on distinguishing reality from artifact, in turn depending on images of highest quality. In radionuclide cardiac imaging, an inferior wall artifactual defect, so called "diaphragmatic attenuation", is particularly common and vexing. Despite the historically held view, analysis and review of the literature suggest the defect is likely not diaphragmatic but rather primarily due to attenuation by nearby stomach wall. The explanation is based on gravity and anatomy. With this improved understanding, effervescent granules were given as a clinical, nonresearch measure to nine patients during myocardial scanning. It was observed that two-thirds demonstrated moderate or marked lessening of attenuation. An additional benefit is lessening of artifact by extracardiac activity. These benefits may also apply to other sorts of cardiac radionuclide imaging. The significance of this new imaging method is discussed and various avenues of research are proposed.

Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2.

PubMed

Tian, Yue; Wu, Xiuying; Guo, Shanbin; Ma, Ling; Huang, Wei; Zhao, Xiaochun

2017-04-01

Minocycline has been demonstrated to exert neuroprotective effects in various experimental models. In the present study, we investigated the mechanisms underlying the protective effects of minocycline on cell injury induced by the inhalation of the anesthetic, sevoflurane. In our in vivo experiments using rats, minocycline attenuated sevoflurane-induced neuronal degeneration and apoptosis in the rat hippocampus, and this effect was associated with the minocycline-mediated suppression of oxidative stress in the hippocampus. In in vitro experiments, minocycline inhibited sevoflurane-induced apoptosis and the production of reactive oxygen species (ROS) in H4 human neuroglioma cells. In addition, minocycline suppressed the sevoflurane-induced upregulation of interleukin (IL)-6 and the activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells. Furthermore, we found that nuclear factor E2-related factor 2 (Nrf2), an activator of the stress response, was upregulated and activated upon sevoflurane treatment both in the rat hippocampus and in H4 cells. In addition, minocycline further augmented the upregulation and activation of Nrf2 when used in conjunction with sevoflurane. Moreover, the knockdown of Nrf2 in H4 cells by small interfering RNA (siRNA) diminished the cytoprotective effect of minocycline, and attenuated the inhibitory effect of minocycline on ROS production, IL-6 upregulation and the activation of the NF-κB signaling pathway. On the whole, our findings indicate that minocycline may exert protective effects against sevoflurane-induced cell injury via the Nrf2-modulated antioxidant response and the inhibition of the activation of the NF-κB signaling pathway.

Chronic heart failure does not attenuate the total activity of sympathetic outflow to skin during whole-body heating.

PubMed

Cui, Jian; Boehmer, John P; Blaha, Cheryl; Lucking, Robert; Kunselman, Allen R; Sinoway, Lawrence I

2013-03-01

Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (≈0.6 °C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (Δ891±110 U/min) and the control subjects (Δ787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (Δ131±29% vs. Δ623±131%; P=0.001). The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin.

Alpha-tocopherol attenuates the anti-tumor activity of crizotinib against cells transformed by NPM-ALK

PubMed Central

Uchihara, Yuki; Ueda, Fumihito; Tago, Kenji; Nakazawa, Yosuke; Ohe, Tomoyuki; Mashino, Tadahiko; Yokota, Shigenobu; Kasahara, Tadashi; Tamura, Hiroomi

2017-01-01

Anaplastic large cell lymphomas (ALCL) are mainly characterized by harboring the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3). We found that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. Although α-tocopherol suppressed the inhibitory effects of crizotinib on the signaling axis including NPM-ALK and STAT3, it had no influence on the intake of crizotinib into cells. Crizotinib also directly inhibited the kinase activity of NPM-ALK; however, this inhibitory effect was not altered by the co-treatment with α-tocopherol. Whereas the nuclear localization of NPM-ALK was disappeared by the treatment with crizotinib, the co-treatment with α-tocopherol swept the effect of crizotinib and caused the localization of NPM-ALK in nucleus. The administration of α-tocopherol attenuated the anti-tumor activity of crizotinib against NPM-ALK-provoked tumorigenesis in vivo. Furthermore, the α-tocopherol-induced inhibition of crizotinib-caused apoptosis was also observed in NPM-ALK-positive cells derived from ALCL patients, namely, SUDHL-1 and Ki-JK. Collectively, these results not only revealed the novel mechanism underlying crizotinib-induced apoptosis in NPM-ALK-positive cells, but also suggest that the anti-tumor effects of crizotinib are attenuated when it is taken in combination with vitamin E. PMID:28806414

PPARγ activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1α and D2

PubMed Central

Festuccia, William T.; Blanchard, Pierre-Gilles; Oliveira, Thiago B.; Magdalon, Juliana; Paschoal, Vivian A.; Richard, Denis

2012-01-01

Here, we investigated whether pharmacological PPARγ activation modulates key early events in brown adipose tissue (BAT) recruitment induced by acute cold exposure with the aim of unraveling the interrelationships between sympathetic and PPARγ signaling. Sprague-Dawley rats treated or not with the PPARγ ligand rosiglitazone (15 mg·kg−1·day−1, 7 days) were kept at 23°C or exposed to cold (5°C) for 24 h and evaluated for BAT gene expression, sympathetic activity, thyroid status, and adrenergic signaling. Rosiglitazone did not affect the reduction in body weight gain and the increase in feed efficiency, V̇o2, and BAT sympathetic activity induced by 24-h cold exposure. Rosiglitazone strongly attenuated the increase in serum total and free T4 and T3 levels and BAT iodothyronine deiodinase type 2 (D2) and PGC-1α mRNA levels and potentiated the reduction in BAT thyroid hormone receptor (THR) β mRNA levels induced by cold. Administration of T3 to rosiglitazone-treated rats exacerbated the cold-induced increase in energy expenditure but did not restore a proper activation of D2 and PGC-1α, nor further increased uncoupling protein 1 expression. Regarding adrenergic signaling, rosiglitazone did not affect the changes in BAT cAMP content and PKA activity induced by cold. Rosiglitazone alone or in combination with cold increased CREB binding to DNA, but it markedly reduced the expression of one of its major coactivators, CREB binding protein. In conclusion, pharmacological PPARγ activation impairs short-term cold elicitation of BAT adrenergic and thyroid signaling, which may result in abnormal tissue recruitment and thermogenic activity. PMID:23100029

Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study

PubMed Central

Jakes, Rupert W; Khaw, Kay-Tee; Day, Nicholas E; Bingham, Sheila; Welch, Ailsa; Oakes, Suzy; Luben, Robert; Dalzell, Nicola; Reeve, Jonathan; Wareham, Nicholas J

2001-01-01

Objectives To study associations between patterns of physical activity and ultrasound attenuation by the heel bone in men and women. Design Cross sectional, population based study. Setting Norfolk. Participants 2296 men and 2914 women aged 45-74 registered with general practices participating in European Prospective Investigation into Cancer (EPIC Norfolk). Results Self reported time spent in high impact physical activity was strongly and positively associated with ultrasound attenuation by the heel bone, independently of age, weight, and other confounding factors. Men who reported participating in ⩾2 hours/week of high impact activity had 8.44 dB/MHz (95% confidence interval 4.49 to 12.40) or 9.5%, higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45 to 4.37) or 3.4% higher. In women this effect was similar in size to that of an age difference of four years. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19 to 1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02 to 0.14) for each additional hour of viewing a week. Conclusions High impact physical activity is independently associated with ultrasound attenuation by the heel bone in men and women. As low ultrasound attenuation has been shown to predict increased risk of hip fracture, interventions to promote participation in high impact activities may help preserve bone density and reduce the risk of fracture. However, in older people such interventions may be inappropriate as they could increase the likelihood of falls. PMID:11159572

Light-attenuating effect of dentin on the polymerization of light-activated restorative resins.

PubMed

Arikawa, Hiroyuki; Kanie, Takahito; Fujii, Koichi; Ban, Seiji; Takahashi, Hideo

2004-12-01

The light-attenuating effect of dentin on the mechanical properties of light-activated composite resins was evaluated using a simple experimental filter. The filter was designed to simulate the light transmittance and light diffusion characteristics of 1.0-mm thick dentin. The depth of cure, surface hardness, and flexural strength for 13 shades of three light-activated restorative resins were examined. These resins were cured either using direct irradiation with a light source, or indirect irradiation through the filter. The attenuation of light intensity by 1.0-mm thick dentin reached 85-90% in the 400-550 nm wavelength region. For all materials, the values of depth of cure, surface hardness on the top and bottom surfaces, and flexural strength of specimens irradiated indirectly through the simulated 1.0-mm thick dentin filter decreased by 37-60%, 16-55%, 50-83%, and 44-82% in comparison with those by direct irradiation, respectively. Recovery from mechanical properties' reduction was achieved when materials were irradiated 1.5-4 times longer than the standard irradiation time.

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever

PubMed Central

Blohmke, Christoph J.; Hill, Jennifer; Darton, Thomas C.; Carvalho-Burger, Matheus; Eustace, Andrew; Jones, Claire; Schreiber, Fernanda; Goodier, Martin R.; Dougan, Gordon; Nakaya, Helder I.; Pollard, Andrew J.

2017-01-01

The mechanisms by which oral, live-attenuated vaccines protect against typhoid fever are poorly understood. Here, we analyze transcriptional responses after vaccination with Ty21a or vaccine candidate, M01ZH09. Alterations in response profiles were related to vaccine-induced immune responses and subsequent outcome after wild-type Salmonella Typhi challenge. Despite broad genetic similarity, we detected differences in transcriptional responses to each vaccine. Seven days after M01ZH09 vaccination, marked cell cycle activation was identified and associated with humoral immunogenicity. By contrast, vaccination with Ty21a was associated with NK cell activity and validated in peripheral blood mononuclear cell stimulation assays confirming superior induction of an NK cell response. Moreover, transcriptional signatures of amino acid metabolism in Ty21a recipients were associated with protection against infection, including increased incubation time and decreased severity. Our data provide detailed insight into molecular immune responses to typhoid vaccines, which could aid the rational design of improved oral, live-attenuated vaccines against enteric pathogens. PMID:29075261

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

PubMed

Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

2018-02-07

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

46 CFR 108.661 - Unit markings: Draft marks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

46 CFR 108.661 - Unit markings: Draft marks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

46 CFR 108.661 - Unit markings: Draft marks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

46 CFR 108.661 - Unit markings: Draft marks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

46 CFR 108.661 - Unit markings: Draft marks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Unit markings: Draft marks. 108.661 Section 108.661... AND EQUIPMENT Equipment Markings and Instructions § 108.661 Unit markings: Draft marks. (a) Each unit must have draft marks for each foot of immersion— (1) If the unit is a surface unit, on both the port...

An iso-α-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice.

PubMed

Hege, Marianne; Jung, Finn; Sellmann, Cathrin; Jin, Chengjun; Ziegenhardt, Doreen; Hellerbrand, Claus; Bergheim, Ina

2018-01-01

Results of in vitro and in vivo studies suggest that consumption of beer is less harmful for the liver than consumption of spirits. It also has been suggested that secondary plant compounds derived from hops such as xanthohumol or iso-α-acids may have beneficial effects on the development of liver diseases of various etiologies. The aim of this study was to determine whether iso-α-acids consumed in doses achieved by "normal" beer consumption have beneficial effects on health. Female C57 Bl/6 J mice, pretreated for 4 d with an iso-α-acid-rich extract (∼30% iso-α-acids from hops, 0.75 mg/kg body weight), were fed one bolus of ethanol (6 g/kg body weight intragastric) or an iso-caloric maltodextrin solution. Markers of liver damage, toll-like receptor-4 signaling, and lipid peroxidation were determined. Furthermore, the effect of isohumulone on the lipopolysaccharide-dependent activation of J774 A.1 macrophages, used as a model of Kupffer cells, was determined. In the liver, acute ethanol administration led to a significant accumulation of fat (∼10-fold), which was accompanied by significantly higher inducible nitric oxide synthase protein level, elevated nitric oxide production, and increased plasminogen activator inhibitor 1 protein concentration when compared to controls. In mice pretreated with iso-α-acids, these effects of alcohol were markedly attenuated. Pretreatment of J774 A.1 macrophages with isohumulone significantly attenuated lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and interleukin-6 as well as the release of nitric oxide. Taken together, iso-α-acids markedly attenuated the development of acute alcohol-induced damage in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer's Disease.

PubMed

Modi, Khushbu K; Roy, Avik; Brahmachari, Saurabh; Rangasamy, Suresh B; Pahan, Kalipada

2015-01-01

This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in attenuating oxidative stress and protecting memory and learning in an animal model of Alzheimer's disease (AD). NaB, but not sodium formate, was found to inhibit LPS-induced production of reactive oxygen species (ROS) in mouse microglial cells. Similarly, NaB also inhibited fibrillar amyloid beta (Aβ)- and 1-methyl-4-phenylpyridinium(+)-induced microglial production of ROS. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on ROS production by mevalonate, and geranylgeranyl pyrophosphate, but not cholesterol, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the antioxidant effect of NaB. Furthermore, we demonstrate that an inhibitor of p21rac geranylgeranyl protein transferase suppressed the production of ROS and that NaB suppressed the activation of p21rac in microglia. As expected, marked activation of p21rac was observed in the hippocampus of subjects with AD and 5XFAD transgenic (Tg) mouse model of AD. However, oral feeding of cinnamon (Cinnamonum verum) powder and NaB suppressed the activation of p21rac and attenuated oxidative stress in the hippocampus of Tg mice as evident by decreased dihydroethidium (DHE) and nitrotyrosine staining, reduced homocysteine level and increased level of reduced glutathione. This was accompanied by suppression of neuronal apoptosis, inhibition of glial activation, and reduction of Aβ burden in the hippocampus and protection of memory and learning in transgenic mice. Therefore, cinnamon powder may be a promising natural supplement in halting or delaying the progression of AD.

Extended Essay Marking on Screen: Is Examiner Marking Accuracy Influenced by Marking Mode?

ERIC Educational Resources Information Center

Johnson, Martin; Hopkin, Rebecca; Shiell, Hannah; Bell, John F.

2012-01-01

In the UK and elsewhere, large-scale educational assessment agencies are shifting the mode of school examination marking towards having examiners mark examination scripts on screen rather than on paper. This shift has prompted questions about whether the mode of marking might influence examiner marking accuracy, particularly in relation to…

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PubMed

Jones, Shannon M; Mann, Adrien; Conrad, Kelsey; Saum, Keith; Hall, David E; McKinney, Lisa M; Robbins, Nathan; Thompson, Joel; Peairs, Abigail D; Camerer, Eric; Rayner, Katey J; Tranter, Michael; Mackman, Nigel; Owens, A Phillip

2018-06-01

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. © 2018 American Heart Association, Inc.

Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

PubMed Central

Xu, Zijian; Wang, Wenjie; Jiang, Kaiju; Yu, Zhou; Huang, Huanwei; Wang, Fengchao; Zhou, Bin; Chen, Ting

2015-01-01

Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation. DOI: http://dx.doi.org/10.7554/eLife.10567.001 PMID:26653852

Progression in attenuating myocardial reperfusion injury: an overview.

PubMed

Bernink, F J P; Timmers, L; Beek, A M; Diamant, M; Roos, S T; Van Rossum, A C; Appelman, Y

2014-01-01

Reperfusion by means of percutaneous coronary intervention or thrombolytic therapy is the most effective treatment for acute myocardial infarction, markedly reducing mortality and morbidity. Reperfusion however induces necrotic and apoptotic damages to cardiomyocytes, that were viable prior to reperfusion, a process called lethal reperfusion injury. This process, consisting of many single processes, may be responsible of up to half of the final infarct size. A myriad of therapies as an adjunct to reperfusion have been studied with the purpose to attenuate reperfusion injury. The majority of these studies have been disappointing or contradicting, but recent proof-of-concept trials show that reperfusion injury still is a legitimate target. This overview will discuss these trials, the progression in attenuating myocardial reperfusion injury, promising therapies, and future perspectives. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pathways of volatile migration in the crust beneath Harrat Lunayyir (Saudi Arabia) during the unrest in 2009 revealed by attenuation tomography

NASA Astrophysics Data System (ADS)

Sychev, Ilya; Koulakov, Ivan; El Khrepy, Sami; Al-Arifi, Nassir

2017-01-01

Harrat Lunayyir is a relatively young basaltic field in Saudi Arabia located at the western margin of the Arabian Peninsula. In April-June 2009, strong seismic activity and ground deformations at this site marked the activation of the magma system beneath Harrat Lunayyir. In this study, we present new three-dimensional models of the attenuation of P and S waves during the unrest in 2009 based on the analysis of t*. We measured 1658 and 3170 values of t* for P and S waves, respectively, for the same earthquakes that were previously used for travel time tomography. The resulting anomalies of the P and S wave attenuation look very similar. In the center of the study area, we observe a prominent high-attenuation pattern, which coincides with the most active seismicity at shallow depths and maximum ground deformations. This high-attenuation zone may represent a zone of accumulation and ascending of gases, which originated at depths of 5-7 km due to the decompression of ascending liquid volatiles. Based on these findings and previous tomography studies, we propose that the unrest at Harrat Lunayyir in 2009 was triggered by a sudden injection of unstable liquid volatiles from deeper magma sources. At some depths, they were transformed to gases, which caused the volume to increase, and this led to seismic activation in the areas of phase transformations. The overpressurized gases ultimately found the weakest point in the rigid basaltic cover at the junction of several tectonic faults and escaped to the surface.

Pathways of volatile migration in the crust beneath Harrat Lunayyir (Saudi Arabia) during the unrest in 2009 revealed by attenuation tomography

NASA Astrophysics Data System (ADS)

El Khrepy, Sami; Koulakov, Ivan; Al-Arifi, Nassir; Sychev, Ilya

2017-04-01

Harrat Lunayyir is a relatively young basaltic field in Saudi Arabia located at the western margin of the Arabian Peninsula. In April-June 2009, strong seismic activity and ground deformations at this site marked the activation of the magma system beneath Harrat Lunayyir. In this study, we present new three-dimensional models of the attenuation of P and S waves during the unrest in 2009 based on the analysis of t*. We measured 1658 and 3170 values of t* for P and S waves, respectively, for the same earthquakes that were previously used for travel time tomography. The resulting anomalies of the P and S wave attenuation look very similar. In the center of the study area, we observe a prominent high-attenuation pattern, which coincides with the most active seismicity at shallow depths and maximum ground deformations. This high-attenuation zone may represent a zone of accumulation and ascending of gases, which originated at depths of 5-7 km due to the decompression of ascending liquid volatiles. Based on these findings and previous tomography studies, we propose that the unrest at Harrat Lunayyir in 2009 was triggered by a sudden injection of unstable liquid volatiles from deeper magma sources. At some depths, they were transformed to gases, which caused the volume to increase, and this led to seismic activation in the areas of phase transformations. The overpressurized gases ultimately found the weakest point in the rigid basaltic cover at the junction of several tectonic faults and escaped to the surface.

Working memory delay period activity marks a domain-unspecific attention mechanism.

PubMed

Katus, Tobias; Müller, Matthias M

2016-03-01

Working memory (WM) recruits neural circuits that also perform perception- and action-related functions. Among the functions that are shared between the domains of WM and perception is selective attention, which supports the maintenance of task-relevant information during the retention delay of WM tasks. The tactile contralateral delay activity (tCDA) component of the event-related potential (ERP) marks the attention-based rehearsal of tactile information in somatosensory brain regions. We tested whether the tCDA reflects the competition for shared attention resources between a WM task and a perceptual task under dual-task conditions. The two tasks were always performed on opposite hands. In different blocks, the WM task had higher or lower priority than the perceptual task. The tCDA's polarity consistently reflected the hand where the currently prioritized task was performed. This suggests that the process indexed by the tCDA is not specific to the domain of WM, but mediated by a domain-unspecific attention mechanism. The analysis of transient ERP components evoked by stimuli in the two tasks further supports the interpretation that the tCDA marks a goal-directed bias in the allocation of selective attention. Larger spatially selective modulations were obtained for stimulus material related to the high-, as compared to low-priority, task. While our results generally indicate functional overlap between the domains of WM and perception, we also found evidence suggesting that selection in internal (mnemonic) and external (perceptual) stimulus representations involves processes that are not active during shifts of preparatory attention. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of the Stimulator of Interferon Genes (STING) adaptor attenuates experimental autoimmune encephalitis

PubMed Central

Lemos, Henrique; Huang, Lei; Chandler, Phillip R.; Mohamed, Eslam; Souza, Guilherme R.; Li, Lingqian; Pacholczyk, Gabriela; Barber, Glen N.; Hayakawa, Yoshihiro; Munn, David H.; Mellor, Andrew L.

2014-01-01

Cytosolic DNA sensing activates the Stimulator of Interferon Genes (STING) adaptor to induce interferon type I (IFNαβ) production. Constitutive DNA sensing to induce sustained STING activation incites tolerance breakdown leading to autoimmunity. Here we show that systemic treatments with DNA nanoparticles (DNPs) induced potent immune regulatory responses via STING signaling that suppressed experimental autoimmune encephalitis (EAE) when administered to mice after immunization with myelin oligodendrocyte glycoprotein (MOG), at EAE onset, or at peak disease severity. DNP treatments attenuated infiltration of effector T cells into the central nervous system (CNS) and suppressed innate and adaptive immune responses to MOG immunization in spleen. Therapeutic responses were not observed in mice treated with cargo DNA or cationic polymers alone, indicating that DNP uptake and cargo DNA sensing by cells with regulatory functions was essential for therapeutic responses to manifest. Intact STING and IFNαβ receptor genes, but not IFNγ receptor genes, were essential for therapeutic responses to DNPs to manifest. Treatments with cyclic diguanylate monophosphate (c-diGMP) to activate STING also delayed EAE onset and reduced disease severity. Therapeutic responses to DNPs were critically dependent on indoleamine 2,3 dioxygenase (IDO) enzyme activity in hematopoietic cells. Thus DNPs and c-diGMP attenuate EAE by inducing dominant T cell regulatory responses via the STING-IFNαβ-IDO pathway that suppress CNS-specific autoimmunity. These findings reveal dichotomous roles for the STING-IFNαβ pathway in either stimulating or suppressing autoimmunity and identify STING activating reagents as a novel class of immune modulatory drugs. PMID:24799564

Attenuation of dichlorvos-induced microglial activation and neuronal apoptosis by 4-hydroxy TEMPO.

PubMed

Sunkaria, Aditya; Sharma, Deep Raj; Wani, Willayat Yousuf; Gill, Kiran Dip

2014-02-01

The neurotoxic consequences of acute high-level as well as chronic low-level organophosphates exposure are associated with a range of abnormalities in nerve functions. Previously, we have shown that after 24 h of dichlorvos exposure, microglia become activated and secrete pro-inflammatory molecules like nitric oxide, tumour necrosis factor-α and interleukin-1β. Here, we extended our findings and focused on the neuronal damage caused by dichlorvos via microglial activation. For this, neurons and microglia were isolated separately from 1-day-old Wistar rat pups. Microglia were treated with dichlorvos for 24 h and supernatant was collected (dichlorvos-induced conditioned medium, DCM). However, when 4-hydroxy TEMPO (4-HT) pretreatment was given, we observed significant attenuation of dichlorvos-induced microglial activation; we also collected the supernatant of this culture (4-HT + DCM, TDCM). Next, we checked the effects of DCM on neurons and found heavy loss in viability as evident from NF-H immunostaining and MTT results, whereas dichlorvos alone-treated neurons showed comparatively less damage. However, we observed significant increase in neuronal viability when cells were treated with TDCM. Semi-quantitative PCR and western blot results revealed significant increase in p53, Bax and cytochrome c levels along with caspase 3 activation after 24 h of DCM treatment. However, TDCM-treated neurons showed significant decrease in the expression of these pro-apoptotic molecules. Taken together, these findings suggest that 4-HT can significantly attenuate dichlorvos-induced microglial activation and prevent apoptotic neuronal cell death.

Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.

PubMed

Mahmoud, Ayman M; Abd El-Twab, Sanaa M; Abdel-Reheim, Eman S

2017-06-01

Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated. Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks. Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina. These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

Blockade of CCN4 attenuates CCl4-induced liver fibrosis.

PubMed

Li, Xiaofei; Chen, Yongxin; Ye, Weiwei; Tao, Xingfei; Zhu, Jinhong; Wu, Shuang; Lou, Lianqing

2015-06-19

CCN4, also termed WNT-inducible signaling pathway protein-1 (WISP-1), has important roles in inflammation and tissue injury. This study aimed to investigate the effect of CCN4 inhibition using monoclonal anti-CCN4 antibody (CCN4mAb) on the liver injury and fibrosis in a mouse model of liver fibrosis. The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received vehicle (saline/olive oil) by subcutaneous injection, CCl4 by subcutaneous injection or CCl4 (subcutaneous) plus CCN4mAb by subcutaneous injection. The pro-inflammatory and pro-fibrotic factors were determined by Western blot. The biochemistry and histopathology, collagen deposition and nuclear factor (NF)-κB activity were also assessed. Chronic CCl4 treatment caused liver injury and collagen accumulation. The expression levels of CCN4, pro-inflammatory and pro-fibrotic mediators as well as the activity of NF-κB were markedly increased. Treatment with CCN4mAb significantly inhibited CCl4-induced CCN4 expression, leading to attenuated CCl4-induced liver injury and the inflammatory response. CCN4 blockade also significantly reduced the formation of collagen in the liver and the expression of α-smooth muscle actin and transforming growth factor β1. CCN4 inhibition by CCN4mAb in vivo significantly attenuated the CCl4-induced liver injury and the progression of liver fibrosis. CCN4 may represent a novel therapeutic target for liver injury and fibrosis.

Improving work zone safety for freight vehicles : effective design patterns for vehicle mounted attenuators.

DOT National Transportation Integrated Search

2010-12-01

This report presents a study of driver perceptions using a driving simulator carried out on the effectiveness of : four markings which vary in striping patterns and color combinations used at the rear of vehicle mounted : attenuators (VMAs) in work z...

Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice.

PubMed

Zhang, Zifeng; Wang, Xin; Zheng, Guihong; Shan, Qun; Lu, Jun; Fan, Shaohua; Sun, Chunhui; Wu, Dongmei; Zhang, Cheng; Su, Weitong; Sui, Junwen; Zheng, Yuanlin

2016-12-25

Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.

Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice

PubMed Central

Zhang, Zifeng; Wang, Xin; Zheng, Guihong; Shan, Qun; Lu, Jun; Fan, Shaohua; Sun, Chunhui; Wu, Dongmei; Zhang, Cheng; Su, Weitong; Sui, Junwen; Zheng, Yuanlin

2016-01-01

Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect. PMID:28029143

Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative injury and calcium oxalate crystal depositions in the rat kidney.

PubMed

Duan, Xiaolu; Kong, Zhenzhen; Mai, Xin; Lan, Yu; Liu, Yang; Yang, Zhou; Zhao, Zhijian; Deng, Tuo; Zeng, Tao; Cai, Chao; Li, Shujue; Zhong, Wen; Wu, Wenqi; Zeng, Guohua

2018-06-01

Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects. In addition, oxalate-induced p38 phosphorylation was significantly attenuated by chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment, whereas the protective effect of chloroquine on rat renal tubular cell oxidative injury was partly reversed by a p38 protein kinase activator anisomycin. Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken together, our results revealed that autophagy inhibition could attenuate oxalate-induced oxidative injury of renal tubular cell and CaOx crystal depositions in the rat kidney via, at least in part, inhibiting the activation of p38 signaling pathway, thus representing a novel role of autophagy in the regulation of oxalate-induced renal oxidative injury and CaOx crystal depositions for the first time. Copyright © 2018. Published by Elsevier B.V.

Attenuation of NADPH oxidase activation and glomerular filtration barrier remodeling with statin treatment.

PubMed

Whaley-Connell, Adam; Habibi, Javad; Nistala, Ravi; Cooper, Shawna A; Karuparthi, Poorna R; Hayden, Melvin R; Rehmer, Nathan; DeMarco, Vincent G; Andresen, Bradley T; Wei, Yongzhong; Ferrario, Carlos; Sowers, James R

2008-02-01

Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation of oxidative stress in the vasculature and the kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition is associated with reductions of oxidative stress in the vasculature and kidney and associated decreases in albuminuria. Effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition on oxidative stress in the kidney and filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse renin transgene and renin-angiotensin system activation, and an immortalized murine podocyte cell line. We treated young, male Ren2 and Sprague-Dawley rats with rosuvastatin (20 mg/kg IP) or placebo for 21 days. Compared with controls, we observed increases in systolic blood pressure, albuminuria, renal NADPH oxidase activity, and 3-nitrotryosine staining, with reductions in the rosuvastatin-treated Ren2. Structural changes on light and transmission electron microscopy, consistent with periarteriolar fibrosis and podocyte foot-process effacement, were attenuated with statin treatment. Nephrin expression was diminished in the Ren2 kidney and trended to normalize with statin treatment. Angiotensin II-dependent increases in podocyte NADPH oxidase activity and subunit expression (NOX2, NOX4, Rac, and p22(phox)) and reactive oxygen species generation were decreased after in vitro statin treatment. These data support a role for increased NADPH oxidase activity and subunit expression with resultant reactive oxygen species formation in the kidney and podocyte. Furthermore, statin attenuation of NADPH oxidase activation and reactive oxygen species formation in the kidney/podocyte seems to play roles in the abrogation of oxidative stress-induced filtration barrier injury and consequent albuminuria.

Porphyra-334, a mycosporine-like amino acid, attenuates UV-induced apoptosis in HaCaT cells.

PubMed

Suh, Sung-Suk; Oh, Se Kyung; Lee, Sung Gu; Kim, Il-Chan; Kim, Sanghee

2017-06-27

The main aim of the current research was to study the effect of porphyra-334, one of mycosporine-like amino acids (MAAs), well known as UV-absorbing compounds, on UVinduced apoptosis in human immortalized keratinocyte (HaCaT) cells. Due to their UV-screening capacity and ability to prevent UV-induced DNA damage, MAAs have recently attracted considerable attention in both industry and research in pharmacology. Herein, human HaCaT cells were used to determine the biological activities of porphyra- 334 by various in vitro assays, including proliferation, apoptosis and Western blot assays. The proliferation rate of UV-irradiated HaCaT cells was significantly decreased compared to the control group. Pretreatment with porphyra- 334 markedly attenuated the inhibitory effect of UV and induced a dramatic decrease in the apoptotic rate. Expression of active caspase-3 protein was increased in response to UV irradiation, while caspase-3 levels were similar between cells treated with porphyra-334 and the non-irradiated control group. Taken together, our data suggest that porphyra-334 inhibits UV-induced apoptosis in HaCaT cells through attenuation of the caspase pathway.

P-wave attenuation in the Pacific slab beneath northeastern Japan revealed by the spectral ratio of intraslab earthquakes

NASA Astrophysics Data System (ADS)

Shiina, Takahiro; Nakajima, Junichi; Matsuzawa, Toru

2018-05-01

We investigate P-wave attenuation, Qp-1, in the Pacific slab beneath northeastern (NE) Japan, adopting for the first time the spectral ratio technique for intraslab earthquakes. When seismograms of two earthquakes are recorded at a station and their ray paths to the station are largely overlapped, station-dependent amplification and structural effects on the overlapped rays can be canceled out from the ratio of the spectral amplitudes of the seismograms. Therefore, adopting the spectral ratio technique for intraslab earthquakes has a great advantage for the precise evaluation of Qp-1 in the slab because the structural effects above the slab, including the high-attenuation mantle wedge, are removed. For estimating the intraslab Qp-1, we determined corner frequency of the intraslab earthquakes using the S-coda wave spectral ratio as the first step. Then, we evaluated the inter-event path attenuation, Δt*, from the ratio of the spectral amplitudes of P waves. The obtained result shows that P-wave attenuation in the Pacific slab marks Qp-1 of 0.0015 (Qp of ∼670) at depths of 50-250 km. This indicates that the P-wave attenuation in the Pacific slab is weaker than that in the mantle wedge. The relatively high-Qp-1 is correlated with the distributions of intraslab earthquakes, suggesting that the P-wave amplitude is more attenuated around active seismicity zones in the slab. Therefore, our observations likely indicate the presence of fractures, hydrous minerals, and dehydrated fluid around seismogenic zones in the slab at intermediate depths.

Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo via inactivation of Akt and activation of JNK

PubMed Central

Budhraja, Amit; Gao, Ning; Zhang, Zhuo; Son, Young-Ok; Cheng, Senping; Wang, Xin; Ding, Songze; Hitron, Andrew; Chen, Gang; Luo, Jia; Shi, Xianglin

2015-01-01

In this study, we investigated the functional role of Akt and JNK signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin-induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 down-regulation, cytochrome c release from mitochondria and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspases activation, and apoptosis. Conversely, LY294002 and a dominant negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of JNK pathway showed marked reduction in apigenin-induced caspases activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth in U937 xenografts accompanied inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens. PMID:22084167

MLAA-based RF surface coil attenuation estimation in hybrid PET/MR imaging

NASA Astrophysics Data System (ADS)

Heußer, Thorsten; Rank, Christopher M.; Freitag, Martin T.; Kachelrieß, Marc

2017-03-01

Attenuation correction (AC) for both patient and hardware attenuation of the 511 keV annihilation photons is required for accurate PET quantification. In hybrid PET/MR imaging, AC for stationary hardware components such as patient table and MR head coil is performed using CT{derived attenuation templates. AC for flexible hardware components such as MR radiofrequency (RF) surface coils is more challenging. Registration{based approaches, aligning scaled CT{derived attenuation templates with the current patient position, have been proposed but are not used in clinical routine. Ignoring RF coil attenuation has been shown to result in regional activity underestimation values of up to 18 %. We propose to employ a modified version of the maximum{ likelihood reconstruction of attenuation and activity (MLAA) algorithm to obtain an estimate of the RF coil attenuation. Starting with an initial attenuation map not including the RF coil, the attenuation update of MLAA is applied outside the body outline only, allowing to estimate RF coil attenuation without changing the patient attenuation map. Hence, the proposed method is referred to as external MLAA (xMLAA). In this work, xMLAA for RF surface coil attenuation estimation is investigated using phantom and patient data acquired with a Siemens Biograph mMR. For the phantom data, average activity errors compared to the ground truth was reduced from -8:1% to +0:8% when using the proposed method. Patient data revealed an average activity underestimation of -6:1% for the abdominal region and -5:3% for the thoracic region when ignoring RF coil attenuation.

Protease-Activated Receptor 1 Inhibition by SCH79797 Attenuates Left Ventricular Remodeling and Profibrotic Activities of Cardiac Fibroblasts

PubMed Central

Sonin, Dmitry L.; Wakatsuki, Tetsuro; Routhu, Kasi V.; Harmann, Leanne M.; Petersen, Matthew; Meyer, Jennifer; Strande, Jennifer L.

2013-01-01

Purpose Fibroblast activity promotes adverse left ventricular (LV) remodeling that underlies the development of ischemic cardiomyopathy. Transforming growth factor-β (TGF-β) is a potent stimulus for fibrosis, and the extracellular signal-regulated kinases(ERK) 1/2 pathway also contributes to the fibrotic response. The thrombin receptor, protease-activated receptor 1 (PAR1), has been shown to play an important role in the excessive fibrosis in different tissues. The aim of this study was to investigate the influence of a PAR1 inhibitor, SCH79797, on cardiac fibrosis, tissue stiffness and postinfarction remodeling, and effects of PAR1 inhibition on thrombin-induced TGF-β and (ERK) 1/2 activities in cardiac fibroblasts. Methods We used a rat model of myocardial ischemia–reperfusion injury, isolated cardiac fibroblasts, and 3-dimensional (3D) cardiac tissue models fabricated to ascertain the contribution of PAR1 activation on cardiac fibrosis and LV remodeling. Results The PAR1 inhibitor attenuated LV dilation and improved LV systolic function of the reperfused myocardium at 28 days. This improvement was associated with a nonsignificant decrease in scar size (%LV) from 23 ± % in the control group (n = 10) to 16% ± 5.5% in the treated group (n = 9; P = .052). In the short term, the PAR1 inhibitor did not rescue infarct size or LV systolic function after 3 days. The PAR1 inhibition abolished thrombin-mediated ERK1/2 phosphorylation, TGF-β and type I procollagen production, matrix metalloproteinase-2/9 activation, myofibroblasts transformation in vitro, and abrogated the remodeling of 3D tissues induced by chronic thrombin treatment. Conclusion These studies suggest PAR1 inhibition initiated after ischemic injury attenuates adverse LV remodeling through late-stage antifibrotic events. PMID:23598708

Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.

PubMed

Yang, Jing; Sun, Lixin; Wang, Lu; Hassan, Hozeifa M; Wang, Xuan; Hylemon, Phillip B; Wang, Tao; Zhou, Huiping; Zhang, Luyong; Jiang, Zhenzhou

2017-01-01

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo . The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro . The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.

Peroxisome proliferator-activated receptor-α activation attenuates 3-nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms.

PubMed

Bhateja, Deepak Kumar; Dhull, Dinesh K; Gill, Aneet; Sidhu, Akramdeep; Sharma, Saurabh; Reddy, B V Krishna; Padi, Satyanarayana S V

2012-01-05

Peroxisome proliferators activated receptor is regarded as potential therapeutic targets to control various neurodegenerative disorders. However, none of the study has elucidated its effect in the treatment of Huntington's disease. We explored whether peroxisome proliferators activated receptor-α agonist may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (3-NP), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-NP (20mg/kg., i.p.) for 4days in rats produced hypolocomotion, muscle incoordination, and cognitive dysfunction. Daily treatment with fenofibrate (100 or 200mg/kg., p.o.), 30min prior to 3-NP administration for a total of 4days, significantly improved the 3-NP induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-NP administration significantly increased oxidative and nitrosative stress (increase lipid peroxidation, protein carbonyls and nitrite level), lactate dehydrogenase activity whereas, decreased the activities of catalase, superoxide dismutase, reduced glutathione, and succinate dehydrogenase. Fenofibrate treatment significantly attenuated oxidative damage, cytokines and improved mitochondrial complexes enzyme activity in brain. In the present study, MK886, a selective inhibitor of peroxisome proliferators activated receptor-α was employed to elucidate the beneficial effect through either receptor dependent or receptor independent neuroprotective mechanisms. Administration of MK886 (1mg/kg, i.p.) prior to fenofibrate (200mg/kg, p.o.) abolished the effect of fenofibrate. The results showed that receptor dependent neuroprotective effects of fenofibrate in 3-NP administered rats provide a new evidence for a role of PPAR-α activation in neuroprotection that is attributed by modulating oxidative stress and inflammation. Copyright © 2011. Published by Elsevier B.V.

Mark-recapture with multiple, non-invasive marks.

PubMed

Bonner, Simon J; Holmberg, Jason

2013-09-01

Non-invasive marks, including pigmentation patterns, acquired scars, and genetic markers, are often used to identify individuals in mark-recapture experiments. If animals in a population can be identified from multiple, non-invasive marks then some individuals may be counted twice in the observed data. Analyzing the observed histories without accounting for these errors will provide incorrect inference about the population dynamics. Previous approaches to this problem include modeling data from only one mark and combining estimators obtained from each mark separately assuming that they are independent. Motivated by the analysis of data from the ECOCEAN online whale shark (Rhincodon typus) catalog, we describe a Bayesian method to analyze data from multiple, non-invasive marks that is based on the latent-multinomial model of Link et al. (2010, Biometrics 66, 178-185). Further to this, we describe a simplification of the Markov chain Monte Carlo algorithm of Link et al. (2010, Biometrics 66, 178-185) that leads to more efficient computation. We present results from the analysis of the ECOCEAN whale shark data and from simulation studies comparing our method with the previous approaches. © 2013, The International Biometric Society.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

PubMed

Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

2017-07-01

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization

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

Hasegawa-Moriyama, Maiko, E-mail: hase-mai@m3.kufm.kagoshima-u.ac.jp; Ohnou, Tetsuya; Godai, Kohei

Highlights: Black-Right-Pointing-Pointer Rosiglitazone attenuated postincisional pain. Black-Right-Pointing-Pointer Rosiglitazone alters macrophage polarization to F4/80{sup +}CD206{sup +} M2 macrophages at the incisional sites. Black-Right-Pointing-Pointer Transplantation of rosiglitazone-treated macrophages produced analgesic effects. -- Abstract: Acute inflammation triggered by macrophage infiltration to injured tissue promotes wound repair and may induce pain hypersensitivity. Peroxisome proliferator-activated receptor {gamma} (PPAR){gamma} signaling is known to regulate heterogeneity of macrophages, which are often referred to as classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages have considerable antimicrobial activity and produce a wide variety of proinflammatory cytokines. In contrast, M2 macrophages are involved in anti-inflammatory and homeostatic functionsmore » linked to wound healing and tissue repair. Although it has been suggested that PPAR{gamma} agonists attenuate pain hypersensitivity, the molecular mechanism of macrophage-mediated effects of PPAR{gamma} signaling on pain development has not been explored. In this study, we investigated the link between the phenotype switching of macrophage polarization induced by PPAR{gamma} signaling and the development of acute pain hypersensitivity. Local administration of rosiglitazone significantly ameliorated hypersensitivity to heat and mechanical stimuli, and paw swelling. Consistent with the down-regulation of nuclear factor {kappa}B (NF{kappa}B) phosphorylation by rosiglitazone at the incisional sites, the number of F4/80{sup +}iNOS{sup +} M1 macrophages was decreased whereas numbers of F4/80{sup +}CD206{sup +} M2 macrophages were increased in rosiglitazone-treated incisional sites 24 h after the procedure. In addition, gene induction of anti-inflammatory M2-macrophage-associated markers such as arginase1, FIZZ1 and interleukin (IL)-10 were significantly increased

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

PubMed

Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

2017-09-01

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4

Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

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

Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.

2012-10-23

The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studiesmore » of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.« less

Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress

PubMed Central

Ślusarczyk, Joanna; Trojan, Ewa; Głombik, Katarzyna; Chamera, Katarzyna; Roman, Adam; Budziszewska, Bogusława; Basta-Kaim, Agnieszka

2016-01-01

The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain. PMID:27239349

Attenuated migration by green tea extract (-)-epigallocatechin gallate (EGCG): involvement of 67 kDa laminin receptor internalization in macrophagic cells.

PubMed

Ren, Xuezhi; Guo, Xingzhi; Chen, Li; Guo, Minxia; Peng, Ning; Li, Rui

2014-08-01

Excessive activation of the microglia in the brain is involved in the development of several neurodegenerative diseases. Previous studies have indicated that (-)-epigallocatechin gallate (EGCG), a major active constituent of green tea, exhibits potent suppressive effects on the activation of microglia. As the 67 kDa laminin receptor (67LR) is a key element in cellular activation and migration, we investigated the effect of EGCG on cell migration and 67LR in lipopolysaccharide (LPS)-activated macrophagic RAW264.7 cells. The presence of EGCG (1-25 μM) markedly attenuated LPS-induced cell migration in a dose-dependent manner. However, the total amount of 67LR protein in the RAW264.7 cells was unaffected by EGCG, as revealed by Western blot analysis. In addition, confocal immunofluorescence microscopy indicated that EGCG caused a marked membrane translocation of 67LR from the membrane surface towards the cytoplasm. Cell-surface biotinylation analysis confirmed that EGCG induced a significant internalization of 67LR by 24-68% in a dose-dependent manner. This study helps to explain the pharmacological action of EGCG on 67LR, suggesting its potential use in the treatment of diseases associated with macrophage/microglia activation, such as neurodegenerative diseases and cancer.

Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

PubMed

Spinosa, Michael; Lu, Guanyi; Su, Gang; Bontha, Sai Vineela; Gehrau, Ricardo; Salmon, Morgan D; Smith, Joseph R; Weiss, Mark L; Mas, Valeria R; Upchurch, Gilbert R; Sharma, Ashish K

2018-05-29

The formation of an abdominal aortic aneurysm (AAA) is characterized by inflammation, macrophage infiltration, and vascular remodeling. In this study, we tested the hypothesis that mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) immunomodulate aortic inflammation, to mitigate AAA formation via modulation of microRNA-147. An elastase-treatment model of AAA was used in male C57BL/6 wild-type (WT) mice. Administration of EVs in elastase-treated WT mice caused a significant attenuation of aortic diameter and mitigated proinflammatory cytokines, inflammatory cell infiltration, an increase in smooth muscle cell α-actin expression, and a decrease in elastic fiber disruption, compared with untreated mice. A 10-fold up-regulation of microRNA (miR)-147, a key mediator of macrophage inflammatory responses, was observed in murine aortic tissue in elastase-treated mice compared with controls on d 14. EVs derived from MSCs transfected with miR-147 mimic, but not with miR-147 inhibitor, attenuated aortic diameter, inflammation, and leukocyte infiltration in elastase-treated mice. In vitro studies of human aortic tissue explants and murine-derived CD11b + macrophages induced proinflammatory cytokines after elastase treatment, and the expression was attenuated by cocultures with EVs transfected with miR-147 mimic, but not with miR-147 inhibitor. Thus, our findings define a critical role of MSC-derived EVs in attenuation of aortic inflammation and macrophage activation via miR-147 during AAA formation.-Spinosa, M., Lu, G., Su, G., Bontha, S. V., Gehrau, R., Salmon, M. D., Smith, J. R., Weiss, M. L., Mas, V. R., Upchurch, G. R., Sharma, A. K. Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147.

Light attenuation in estuarine mangrove lakes

NASA Astrophysics Data System (ADS)

Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.

2017-01-01

Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (<2 m depth) mangrove-surrounded lakes in two sub-estuaries in the coastal Everglades, Florida USA. Turbidity, chromophoric dissolved organic matter (CDOM), and phytoplankton chlorophyll a (chl a) were measured concurrently and their respective contributions to the light attenuation rate were estimated. Light transmission to the benthos relative to literature estimates of minimum requirements for SAV growth indicated that the underwater light environment was often unsuitable for SAV. Light attenuation rates (n = 417) corrected for solar elevation angles ranged from 0.16 m-1 to 9.83 m-1 with a mean of 1.73 m-1. High concentrations of CDOM with high specific light absorption contributed the most to light attenuation followed by turbidity and chl a. CDOM alone sufficiently reduces light transmission beyond the estimated limits for SAV growth, making it difficult for ecosystem managers to increase SAV abundance by management activities. Light limitation of SAV in these areas may be a persistent feature because of their proximity to CDOM source materials from the surrounding mangrove swamp. Increasing freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

Houttuynia cordata attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells.

PubMed

Kang, Hyun; Koppula, Sushruta

2014-01-01

Houttuynia cordata (H. cordata) from the family Saururaceae is a perennial herb native to Southeast Asia. It possesses a range of medicinal properties to treat several disease symptoms including allergic inflammation and anaphylaxis. In the present investigation, we provided the molecular mechanisms underlying the role of H. cordata extract (HCE) in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. HepG2 cells were pre-treated with various concentrations of HCE (0, 10, 20, 40, and 80 μg/mL) and treated with serum-free medium with normal glucose (5 mM) for 1 h, followed by exposure to high glucose (25 mM D-glucose) for 24 h. HCE significantly and dose-dependently attenuated lipid accumulation in human HepG2 hepatocytes when exposed to high glucose (25 mM D-glucose) (p < 0.05, p < 0.01 and p < 0.001 at 20, 40, and 80 μg/mL concentrations, respectively). Further, HCE attenuated the expression of fatty acid synthase (FAS), sterol regulatory element-binding protein-1 and glycerol 3-phosphate acyltransferases (GPATs). The adenosine monophosphate-activated protein kinase (AMPK) was also activated by HCE treatment when exposed to high glucose (25 mM D-glucose) in human HepG2 hepatocytes. This study suggests the hypolipidemic effects of HCE by the inhibition of lipid biosynthesis mediated through AMPK signaling, which may play an active role and can be developed as an anti-obesity agent.

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling.

PubMed

Lu, Yunyang; Feng, Yingda; Liu, Dan; Zhang, Zhiran; Gao, Kai; Zhang, Wei; Tang, Haifeng

2018-06-15

Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protection are available at present. Therefore, this study was conducted aiming to investigate the protective effect of TQ against MI/R injury and to clarify its potential mechanism. MI/R injury models of isolated rat hearts and neonatal rat cardiomyocytes were established. The Langendorff isolated perfused heart system, triphenyltetrazolium chloride staining, gene transfection, TransLaser scanning confocal microscopy, and western blotting were employed to evaluate the cardioprotection effect of TQ against MI/R injury. Compared with the MI/R group, TQ treatment could remarkably improve left ventricular function, decrease myocardial infarct size and production of lactate dehydrogenase (LDH), and attenuate mitochondrial oxidative damage by elevating superoxide dismutase (SOD) activity and reducing production of hydrogen peroxide (H2O2) and malonaldehyde (MDA). Moreover, the cardioprotective effect of TQ was accompanied by up-regulated expression of SIRT1 and inhibition of p53 acetylation. Additionally, TQ treatment could also enhance mitochondrial function and reduce the number of apoptotic cardiomyocytes. Nonetheless, the cardioprotective effect of TQ could be mitigated by SIRT1 inhibitor sirtinol and SIRT1 siRNA, respectively, which was achieved through inhibition of the SIRT1 signaling pathway. The findings in this study demonstrate that TQ is efficient in attenuating MI/R injury through activation of the SIRT1 signaling pathway, which can thus reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice

PubMed Central

Bhattacharya, Parna; Dey, Ranadhir; Dagur, Pradeep K.; Kruhlak, Michael; Ismail, Nevien; Debrabant, Alain; Joshi, Amritanshu B.; Akue, Adovi; Kukuruga, Mark; Takeda, Kazuyo; Selvapandiyan, Angamuthu; McCoy, John Philip

2015-01-01

Visceral leishmaniasis (VL) causes significant mortality and there is no effective vaccine. Previously, we have shown that genetically modified Leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. In this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from BALB/c mice both in vitro and in vivo. In vitro infection of macrophages with live attenuated parasites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-12 [IL-12], gamma interferon [IFN-γ], and IL-6), chemokines (monocyte chemoattractant protein 1/CCL-2, macrophage inflammatory protein 1α/CCL-3, and IP-10), reactive oxygen species (ROS), and nitric oxide, while concomitantly reducing anti-inflammatory cytokine IL-10 and arginase-1 activities, suggesting a dominant classically activated/M1 macrophage response. The classically activated response in turn helps in presenting antigen to T cells, as observed with robust CD4+ T cell activation in vitro. Similarly, parasitized splenic macrophages from live attenuated parasite-infected mice also demonstrated induction of an M1 macrophage phenotype, indicated by upregulation of IL-1β, TNF-α, IL-12, and inducible nitric oxide synthase 2 and downregulation of genes associated with the M2 phenotype, i.e., the IL-10, YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice. Furthermore, an ex vivo antigen presentation assay showed macrophages from live attenuated parasite-infected mice induced higher IFN-γ and IL-2 but significantly less IL-10 production by ovalbumin-specific CD4+ T cells, resulting in proliferation of Th1 cells. These data suggest that infection with live attenuated parasites promotes a state of classical activation (M1 dominant) in macrophages that

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice.

PubMed

Bhattacharya, Parna; Dey, Ranadhir; Dagur, Pradeep K; Kruhlak, Michael; Ismail, Nevien; Debrabant, Alain; Joshi, Amritanshu B; Akue, Adovi; Kukuruga, Mark; Takeda, Kazuyo; Selvapandiyan, Angamuthu; McCoy, John Philip; Nakhasi, Hira L

2015-10-01

Visceral leishmaniasis (VL) causes significant mortality and there is no effective vaccine. Previously, we have shown that genetically modified Leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. In this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from BALB/c mice both in vitro and in vivo. In vitro infection of macrophages with live attenuated parasites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-12 [IL-12], gamma interferon [IFN-γ], and IL-6), chemokines (monocyte chemoattractant protein 1/CCL-2, macrophage inflammatory protein 1α/CCL-3, and IP-10), reactive oxygen species (ROS), and nitric oxide, while concomitantly reducing anti-inflammatory cytokine IL-10 and arginase-1 activities, suggesting a dominant classically activated/M1 macrophage response. The classically activated response in turn helps in presenting antigen to T cells, as observed with robust CD4(+) T cell activation in vitro. Similarly, parasitized splenic macrophages from live attenuated parasite-infected mice also demonstrated induction of an M1 macrophage phenotype, indicated by upregulation of IL-1β, TNF-α, IL-12, and inducible nitric oxide synthase 2 and downregulation of genes associated with the M2 phenotype, i.e., the IL-10, YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice. Furthermore, an ex vivo antigen presentation assay showed macrophages from live attenuated parasite-infected mice induced higher IFN-γ and IL-2 but significantly less IL-10 production by ovalbumin-specific CD4(+) T cells, resulting in proliferation of Th1 cells. These data suggest that infection with live attenuated parasites promotes a state of classical activation (M1 dominant) in macrophages that

Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

PubMed

Gu, Qi; Wang, Bing; Zhang, Xiao-Feng; Ma, Yan-Ping; Liu, Jian-Dong; Wang, Xiao-Ze

2014-08-01

Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation

PubMed Central

2011-01-01

Background Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. Methods Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7). Results Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD3, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002). Conclusions Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain. PMID:21676267

Spatial distribution of intrinsic and scattering seismic attenuation in active volcanic islands - I: model and the case of Tenerife Island

NASA Astrophysics Data System (ADS)

Prudencio, Janire; Del Pezzo, Edoardo; García-Yeguas, Araceli; Ibáñez, Jesús M.

2013-12-01

The complex volcanic system of Tenerife Island is known to have a highly heterogeneous character, as recently confirmed by velocity tomography. We present new information derived from intrinsic quality factor inverse maps (Qi-1), scattering quality factor inverse maps (Qs-1) and total quality factor inverse maps (Qt-1) obtained for the same region. The data set used in this work is the result of the analysis of an active seismic experiment carried out, using offshore shots (air guns) recorded at over 85 onshore seismic stations. The estimates of the attenuation parameters are based on the assumption that the seismogram energy envelopes are determined by seismic energy diffusion processes occurring inside the island. Diffusion model parameters, proportional to Qi-1 and to Qs-1, are estimated from the inversion of the energy envelopes for any source-receiver couple. They are then weighted with a new graphical approach based on a Gaussian space probability function, which allowed us to create `2-D probabilistic maps' representing the space distribution of the attenuation parameters. The 2-D images obtained reveal the existence of a zone in the centre of the island characterized by the lowest attenuation effects. This effect is interpreted as highly rigid and cooled rocks. This low-attenuation region is bordered by zones of high attenuation, associated with the recent historical volcanic activity. We calculate the transport mean free path obtaining a value of around 4 km for the frequency range 6-12 Hz. This result is two orders of magnitude smaller than values calculated for the crust of the Earth. An absorption length between 10 and 14 km is associated with the average intrinsic attenuation parameter. These values, while small in the context of tectonic regions, are greater than those obtained in volcanic regions such as Vesuvius or Merapi. Such differences may be explained by the magnitude of the region of study, over three times larger than the aforementioned study

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

PubMed

Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

Mark-resight abundance estimation under incomplete identification of marked individuals

USGS Publications Warehouse

McClintock, Brett T.; Hill, Jason M.; Fritz, Lowell; Chumbley, Kathryn; Luxa, Katie; Diefenbach, Duane R.

2014-01-01

Often less expensive and less invasive than conventional mark–recapture, so-called 'mark-resight' methods are popular in the estimation of population abundance. These methods are most often applied when a subset of the population of interest is marked (naturally or artificially), and non-invasive sighting data can be simultaneously collected for both marked and unmarked individuals. However, it can often be difficult to identify marked individuals with certainty during resighting surveys, and incomplete identification of marked individuals is potentially a major source of bias in mark-resight abundance estimators. Previously proposed solutions are ad hoc and will tend to underperform unless marked individual identification rates are relatively high (>90%) or individual sighting heterogeneity is negligible.Based on a complete data likelihood, we present an approach that properly accounts for uncertainty in marked individual detection histories when incomplete identifications occur. The models allow for individual heterogeneity in detection, sampling with (e.g. Poisson) or without (e.g. Bernoulli) replacement, and an unknown number of marked individuals. Using a custom Markov chain Monte Carlo algorithm to facilitate Bayesian inference, we demonstrate these models using two example data sets and investigate their properties via simulation experiments.We estimate abundance for grassland sparrow populations in Pennsylvania, USA when sampling was conducted with replacement and the number of marked individuals was either known or unknown. To increase marked individual identification probabilities, extensive territory mapping was used to assign incomplete identifications to individuals based on location. Despite marked individual identification probabilities as low as 67% in the absence of this territorial mapping procedure, we generally found little return (or need) for this time-consuming investment when using our proposed approach. We also estimate rookery abundance

Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite.

PubMed

Damacena-Angelis, Célio; Oliveira-Paula, Gustavo H; Pinheiro, Lucas C; Crevelin, Eduardo J; Portella, Rafael L; Moraes, Luiz Alberto B; Tanus-Santos, Jose E

2017-08-01

Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR) mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion) to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite ( 15 N-nitrite) by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Nitrate exerted no effect on aortic accumulation of 15 N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in the

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

PubMed Central

Hwang, Tsong-Long; Shen, Hsin-I; Liu, Fu-Chao; Tsai, Hsin-I; Wu, Yang-Chang; Chang, Fang-Rong; Yu, Huang-Ping

2014-01-01

Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats. PMID:25360589

Physical activity attenuates age-related biomarker alterations in preclinical AD

PubMed Central

Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L.; Dowling, N.M.; Carlsson, Cynthia M.; Bendlin, Barbara B.; LaRue, Asenath; Rowley, Howard A.; Christian, Brad T.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark A.

2014-01-01

Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n = 186) and 18F-fluorodeoxyglucose–PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. PMID:25298312

Physical activity attenuates age-related biomarker alterations in preclinical AD.

PubMed

Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L; Dowling, N M; Carlsson, Cynthia M; Bendlin, Barbara B; LaRue, Asenath; Rowley, Howard A; Christian, Brad T; Asthana, Sanjay; Hermann, Bruce P; Johnson, Sterling C; Sager, Mark A

2014-11-04

To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. © 2014 American Academy of Neurology.

Action-related auditory ERP attenuation: Paradigms and hypotheses.

PubMed

Horváth, János

2015-11-11

A number studies have shown that the auditory N1 event-related potential (ERP) is attenuated when elicited by self-induced or self-generated sounds. Because N1 is a correlate of auditory feature- and event-detection, it was generally assumed that N1-attenuation reflected the cancellation of auditory re-afference, enabled by the internal forward modeling of the predictable sensory consequences of the given action. Focusing on paradigms utilizing non-speech actions, the present review summarizes recent progress on action-related auditory attenuation. Following a critical analysis of the most widely used, contingent paradigm, two further hypotheses on the possible causes of action-related auditory ERP attenuation are presented. The attention hypotheses suggest that auditory ERP attenuation is brought about by a temporary division of attention between the action and the auditory stimulation. The pre-activation hypothesis suggests that the attenuation is caused by the activation of a sensory template during the initiation of the action, which interferes with the incoming stimulation. Although each hypothesis can account for a number of findings, none of them can accommodate the whole spectrum of results. It is suggested that a better understanding of auditory ERP attenuation phenomena could be achieved by systematic investigations of the types of actions, the degree of action-effect contingency, and the temporal characteristics of action-effect contingency representation-buildup and -deactivation. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015. Published by Elsevier B.V.

The Association Between Sedentary Behavior and Cognitive Function Among Older Adults May Be Attenuated With Adequate Physical Activity.

PubMed

Edwards, Meghan K; Loprinzi, Paul D

2017-01-01

Examine the independent association of sedentary behavior and cognitive function in older adults, as well as whether physical activity attenuates this potential association. Data from the 1999-2002 National Health and Nutrition Examination Survey were used (N = 2472 adults 60 to 85 yrs). Sedentary behavior was subjectively assessed and the Digit Symbol Substitution Test (DSST) was employed to assess cognitive function. Among an unadjusted and an adjusted model not accounting for physical activity, only 5+ hrs/day (vs. < 1 hr) of sedentary time was independently associated with lower DSST scores (β = -3.1; 95% CI: -5.8 to -0.4; P= .02). However, a fully adjusted model (adding in moderate-to-vigorous physical activity as a covariate) did not yield a statistically significant association between 5+ hrs/day of sedentary time and DSST scores (β = -2.5; 95% CI: -5.1 to 0.2; P = .07). Accumulated daily sedentary behavior of 5+ hrs is associated with lower cognitive function in an older adult population when physical activity is not taken into account. However, physical activity may account for 19% of the total association between sedentary behavior and cognitive function, thus attenuating the sedentary-cognitive function association. Efforts should be made to promote physical activity in the aging population.

OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

PubMed

Collins, Valerie M; Daly, Donna M; Liaskos, Marina; McKay, Neil G; Sellers, Donna; Chapple, Christopher; Grundy, David

2013-11-01

To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures. Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release. These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves. © 2013 The Authors. BJU International © 2013 BJU International.

Isoflurane-Induced Caspase-3 Activation Is Dependent on Cytosolic Calcium and Can Be Attenuated by Memantine

PubMed Central

Zhang, Guohua; Dong, Yuanlin; Zhang, Bin; Ichinose, Fumito; Wu, Xu; Culley, Deborah J.; Crosby, Gregory

2008-01-01

Increasing evidence indicates that caspase activation and apoptosis are associated with a variety of neurodegenerative disorders, including Alzheimer's disease. We reported that anesthetic isoflurane can induce apoptosis, alter processing of the amyloid precursor protein (APP), and increase amyloid-β protein (Aβ) generation. However, the mechanism by which isoflurane induces apoptosis is primarily unknown. We therefore set out to assess effects of extracellular calcium concentration on isoflurane-induced caspase-3 activation in H4 human neuroglioma cells stably transfected to express human full-length APP (H4-APP cells). In addition, we tested effects of RNA interference (RNAi) silencing of IP3 receptor, NMDA receptor, and endoplasmic reticulum (ER) calcium pump, sacro-/ER calcium ATPase (SERCA1). Finally, we examined the effects of the NMDA receptor partial antagonist, memantine, in H4-APP cells and brain tissue of naive mice. EDTA (10 mm), BAPTA (10 μm), and RNAi silencing of IP3 receptor, NMDA receptor, or SERCA1 attenuated capase-3 activation. Memantine (4 μm) inhibited isoflurane-induced elevations in cytosolic calcium levels and attenuated isoflurane-induced caspase-3 activation, apoptosis, and cell viability. Memantine (20 mg/kg, i.p.) reduced isoflurane-induced caspase-3 activation in brain tissue of naive mice. These results suggest that disruption of calcium homeostasis underlies isoflurane-induced caspase activation and apoptosis. We also show for the first time that the NMDA receptor partial antagonist, memantine, can prevent isoflurane-induced caspase-3 activation and apoptosis in vivo and in vitro. These findings, indicating that isoflurane-induced caspase activation and apoptosis are dependent on cytosolic calcium levels, should facilitate the provision of safer anesthesia care, especially for Alzheimer's disease and elderly patients. PMID:18434534

MRI-guided attenuation correction in whole-body PET/MR: assessment of the effect of bone attenuation.

PubMed

Akbarzadeh, A; Ay, M R; Ahmadian, A; Alam, N Riahi; Zaidi, H

2013-02-01

Hybrid PET/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies.

Assessment of attenuated Salmonella vaccine strains in controlling experimental Salmonella Typhimurium infection in chickens

PubMed Central

Pei, Yanlong; Parreira, Valeria R.; Roland, Kenneth L.; Curtiss, Roy; Prescott, John F.

2014-01-01

Salmonella hold considerable promise as vaccine delivery vectors for heterologous antigens in chickens. Such vaccines have the potential additional benefit of also controlling Salmonella infection in immunized birds. As a way of selecting attenuated strains with optimal immunogenic potential as antigen delivery vectors, this study screened 20 novel Salmonella Typhimurium vaccine strains, differing in mutations associated with delayed antigen synthesis and delayed attenuation, for their efficacy in controlling colonization by virulent Salmonella Typhimurium, as well as for their persistence in the intestine and the spleen. Marked differences were observed between strains in these characteristics, which provide the basis for selection for further study as vaccine vectors. PMID:24396177

Assessment of attenuated Salmonella vaccine strains in controlling experimental Salmonella Typhimurium infection in chickens.

PubMed

Pei, Yanlong; Parreira, Valeria R; Roland, Kenneth L; Curtiss, Roy; Prescott, John F

2014-01-01

Salmonella hold considerable promise as vaccine delivery vectors for heterologous antigens in chickens. Such vaccines have the potential additional benefit of also controlling Salmonella infection in immunized birds. As a way of selecting attenuated strains with optimal immunogenic potential as antigen delivery vectors, this study screened 20 novel Salmonella Typhimurium vaccine strains, differing in mutations associated with delayed antigen synthesis and delayed attenuation, for their efficacy in controlling colonization by virulent Salmonella Typhimurium, as well as for their persistence in the intestine and the spleen. Marked differences were observed between strains in these characteristics, which provide the basis for selection for further study as vaccine vectors.

The Seismic Attenuation Structure of the East Pacific Rise

DTIC Science & Technology

1992-02-27

Kanamori, R. W. Clayton, Three- dimensional attenuation structure of Kilauea -East rift zone, Hawaii , J. Geophys. Res., submitted, 1990. Holt, M., Underwater...and J. J. Zucca, Active high-resolution seismic tomography of compressional wave velocity and attenuation at Medicine Lake volcano , northern California...zones of anomalously high S-wave attenuation in the upper crust near Ruapehu and Ngauruhoe volcanoes , New Zealand, J. Volcanol. Geotherm. Res., 10, 125

Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase.

PubMed

Bearden, Scott W; Sexton, Christopher; Pare, Joshua; Fowler, Janet M; Arvidson, Cindy G; Yerman, Lyudmyla; Viola, Ronald E; Brubaker, Robert R

2009-01-01

It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6-phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not detectable in epidemic Y. pestis due to missense mutations (substitution of proline for serine at amino position 155 of Zwf and leucine for valine at position 363 of AspA). In this study, functional Zwf was found in pestoides strains E, F and G but not seven other enzootic isolates; enzymic activity was associated with retention of serine at amino acid position 155. Essentially, full AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity occurred in strains Angola and A16, which contained phenylalanine at this position. The kcat but not Km of purified AspA from strain Angola was significantly reduced. In this context, aspA of the recently described attenuated enzootic microtus biovar encodes active valine at position 363, further indicating that functional AspA is a biomarker for avirulence of Y. pestis in man.

DC attenuation meter

DOEpatents

Hargrove, Douglas L.

2004-09-14

A portable, hand-held meter used to measure direct current (DC) attenuation in low impedance electrical signal cables and signal attenuators. A DC voltage is applied to the signal input of the cable and feedback to the control circuit through the signal cable and attenuators. The control circuit adjusts the applied voltage to the cable until the feedback voltage equals the reference voltage. The "units" of applied voltage required at the cable input is the system attenuation value of the cable and attenuators, which makes this meter unique. The meter may be used to calibrate data signal cables, attenuators, and cable-attenuator assemblies.

Attenuating Ischemic Disruption of K+ Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.

PubMed

Chao, Dongman; Wang, Qinyu; Balboni, Gianfranco; Ding, Guanghong; Xia, Ying

2016-12-01

Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K + homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K + homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K + homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K + homeostasis in the neonatal cortex. Since maintaining cellular K + homeostasis and inhibiting excessive K + fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K + homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.

Activation of peroxisome proliferator-activated receptor δ induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome

PubMed Central

Tanaka, Toshiya; Yamamoto, Joji; Iwasaki, Satoshi; Asaba, Hiroshi; Hamura, Hiroki; Ikeda, Yukio; Watanabe, Mitsuhiro; Magoori, Kenta; Ioka, Ryoichi X.; Tachibana, Keisuke; Watanabe, Yuichiro; Uchiyama, Yasutoshi; Sumi, Koichi; Iguchi, Haruhisa; Ito, Sadayoshi; Doi, Takefumi; Hamakubo, Takao; Naito, Makoto; Auwerx, Johan; Yanagisawa, Masashi; Kodama, Tatsuhiko; Sakai, Juro

2003-01-01

In this study, we defined the role of peroxisome proliferator-activated receptor β/δ (PPARδ) in metabolic homeostasis by using subtype selective agonists. Analysis of rat L6 myotubes treated with the PPARδ subtype-selective agonist, GW501516, by the Affymetrix oligonucleotide microarrays revealed that PPARδ controls fatty acid oxidation by regulating genes involved in fatty acid transport, β-oxidation, and mitochondrial respiration. Similar PPARδ-mediated gene activation was observed in the skeletal muscle of GW501516-treated mice. Accordingly, GW501516 treatment induced fatty acid β-oxidation in L6 myotubes as well as in mouse skeletal muscles. Administration of GW501516 to mice fed a high-fat diet ameliorated diet-induced obesity and insulin resistance, an effect accompanied by enhanced metabolic rate and fatty acid β-oxidation, proliferation of mitochondria, and a marked reduction of lipid droplets in skeletal muscles. Despite a modest body weight change relative to vehicle-treated mice, GW501516 treatment also markedly improved diabetes as revealed by the decrease in plasma glucose and blood insulin levels in genetically obese ob/ob mice. These data suggest that PPARδ is pivotal to control the program for fatty acid oxidation in the skeletal muscle, thereby ameliorating obesity and insulin resistance through its activation in obese animals. PMID:14676330

Mark.

ERIC Educational Resources Information Center

Lipman, Matthew; Smith, Theresa L., Ed.

Mark is the central character in this story designed to help adolescents formulate a philosophy of values. The story is well suited for use in high school social studies courses and/or in philosophy or guidance units. Mark's thoughts and actions are reported as he interacts with his family, friends, acquaintances, and individuals of authority…

Crustal structure of the Alps as seen by attenuation tomography

NASA Astrophysics Data System (ADS)

Mayor, Jessie; Calvet, Marie; Margerin, Ludovic; Vanderhaeghe, Olivier; Traversa, Paola

2016-04-01

between low-attenuation regions to the North and high-attenuation region to the South correlates geographically with the location of the Periadriatic Lineament (PL), a major late-alpine crustal- to lithospheric-scale structure. Furthermore, the attenuation structure seems to prolong the PL to the West along a line marked by large historical earthquakes. The Apennines orogenic belts exhibit a distinct frequency behavior, with high attenuation at low-frequency and low-attenuation at high-frequency. Low-frequency absorption may likely be explained by the relatively thick cover of Cenozoic sedimentary materials, as well as by shallow geothermal activity. We hypothesize that the frequency dependence of the attenuation structure, in particular in the Apennines, is caused by a change of the wavefield composition which accentuates the sensitivity of the coda to the deeper parts of the medium as the frequency increases.

PET attenuation coefficients from CT images: experimental evaluation of the transformation of CT into PET 511-keV attenuation coefficients.

PubMed

Burger, C; Goerres, G; Schoenes, S; Buck, A; Lonn, A H R; Von Schulthess, G K

2002-07-01

The CT data acquired in combined PET/CT studies provide a fast and essentially noiseless source for the correction of photon attenuation in PET emission data. To this end, the CT values relating to attenuation of photons in the range of 40-140 keV must be transformed into linear attenuation coefficients at the PET energy of 511 keV. As attenuation depends on photon energy and the absorbing material, an accurate theoretical relation cannot be devised. The transformation implemented in the Discovery LS PET/CT scanner (GE Medical Systems, Milwaukee, Wis.) uses a bilinear function based on the attenuation of water and cortical bone at the CT and PET energies. The purpose of this study was to compare this transformation with experimental CT values and corresponding PET attenuation coefficients. In 14 patients, quantitative PET attenuation maps were calculated from germanium-68 transmission scans, and resolution-matched CT images were generated. A total of 114 volumes of interest were defined and the average PET attenuation coefficients and CT values measured. From the CT values the predicted PET attenuation coefficients were calculated using the bilinear transformation. When the transformation was based on the narrow-beam attenuation coefficient of water at 511 keV (0.096 cm(-1)), the predicted attenuation coefficients were higher in soft tissue than the measured values. This bias was reduced by replacing 0.096 cm(-1) in the transformation by the linear attenuation coefficient of 0.093 cm(-1) obtained from germanium-68 transmission scans. An analysis of the corrected emission activities shows that the resulting transformation is essentially equivalent to the transmission-based attenuation correction for human tissue. For non-human material, however, it may assign inaccurate attenuation coefficients which will also affect the correction in neighbouring tissue.

Enamel-based mark performance for marking Chinese mystery snail Bellamya chinensis

USGS Publications Warehouse

Wong, Alec; Allen, Craig R.; Hart, Noelle M.; Haak, Danielle M.; Pope, Kevin L.; Smeenk, Nicholas A.; Stephen, Bruce J.; Uden, Daniel R.

2013-01-01

The exoskeleton of gastropods provides a convenient surface for carrying marks, and i the interest of improving future marking methods our laboratory assessed the performance of an enamel paint. The endurance of the paint was also compared to other marking methods assessed in the past. We marked the shells of 30 adult Chinese mystery snails Bellamya chinensis and held them in an aquarium for 181 days. We observed no complete degradation of any enamel-paint mark during the 181 days. The enamel-paint mark was superior to a nai;-polish mark, which lasted a median of 100 days. Enamel-paint marks also have a lower rate of loss (0.00 month-1 181 days) than plastic bee tags (0.01 month-1, 57 days), gouache paint (0.07 month-1, 18.5 days), or car body paint from studies found in scientific literature. Legibility of enamel-paint marks had a median lifetime of 102 days. The use of enamel paint on the shells of gastropods is a viable option for studies lasting up to 6 months. Furthermore, visits to capture-mark-recapture site 1 year after application of enamel-paint marks on B. chinesnis shells produced several individuals on which the enamel paint was still visible, although further testing is required to clarify durability over longer periods.

Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.

PubMed

Wang, Zhuo; Ma, Lijuan; Wang, Xuebin; Cai, Heping; Huang, Jin; Liu, Jiyong; Hu, Jinhong; Su, Dingfeng

2014-08-01

We investigated E-selectin expression in mice and rabbits with vinorelbine-induced phlebitis and the effect of cimetidine. To find the relationship between E-selectin expression and vinorelbine-induced phlebitis. Mouse and rabbit model of vinorelbine-induced phlebitis was established by intravenous infusion of vinorelbine. Pathological observation, molecular-biological determination of E-selectin and protein function of it was evaluated. Grossly, we observed swelling, edema and cord-like vessel changes in mice receiving vinorelbine but only mild edema in mice pretreated with cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine-treated mice and 17 for mice pretreated with cimetidine (P < 0.05). ELISA revealed that rabbits treated with vinorelbine had markedly higher serum contents of E-selectin than normal saline (NS) controls (vinorelbine 1.534 ± 0.449 vs. NS 0.746 ± 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine (cimetidine 0.717 ± 0.468 vs. vinorelbine 1.534 ± 0.449 ng/mL, P < 0.05). Rose Bengal staining assays showed that vinorelbine markedly increased the adhesion rate of neutrophils for endothelial cells (vinorelbine 38.70 ± 8.34% vs. controls 8.93 ± 4.85%, P < 0.01), which, however, was significantly suppressed by cimetidine (9.93 ± 5.91%, P < 0.01 vs. vinorelbine). In E-selectin knockout mice, we found no apparent difference in tail swelling in mice receiving vinorelbine or cimetidine and vinorelbine. In conclusion, cimetidine attenuates vinorelbine-induced phlebitis in mice probably by suppressing increased expression of E-selectin.

Esculin attenuates endotoxin shock induced by lipopolysaccharide in mouse and NO production in vitro through inhibition of NF-κB activation.

PubMed

Li, Weifeng; Wang, Yu; Wang, Xiumei; He, Zehong; Liu, Fang; Zhi, Wenbing; Zhang, Hailin; Niu, Xiaofeng

2016-11-15

Esculin, a coumarin compound derived from the traditional Chinese herbs such as Cortex Fraxini, has long been used for treating inflammatory and vascular diseases. In present study, we analyzed the role of esculin against macrophages and endotoxin shock induced by lipopolysaccharide (LPS) in mice. Here, we demonstrated that esculin suppressed inflammatory reactions in macrophages and protected mice from LPS-induced endotoxin shock. We found that esculin significantly inhibited the production of nitric oxide (NO) production via the inhibition of nuclear factor-κB (NF-κB) activation in macrophages. In animal model, esculin pretreatment significantly improved the survival rate of mice. LPS-induced increase of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum, lung, liver and kidney were markedly inhibited by esculin. IL-10, an anti-inflammatory cytokine, was up-regulated by esculin. Moreover, the histopathological analyses showed that esculin significantly attenuated the tissues injury of lung, liver, kidney in endotoxic mice. In addition, esculin significantly diminished the protein expression of NF-κB p65 in lung, liver, kidney, which resulted in lower levels of inflammatory mediators. These results suggest that esculin may be a potential drug for treatment of various inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

On denture marking.

PubMed

Borrman, H I; DiZinno, J A; Wasén, J; René, N

1999-06-01

During the last decades in Sweden dentures have been permanently marked with a stainless steel metal band incorporated into the acrylic and containing the patient's birth date, a special number, and "S" for Sweden. The last recommendation issued by the National Board of Health and Welfare states that "the patients shall always be offered denture marking and be informed about the benefit thereof. Denture marking is not permitted if the patient refuses it". Requirements for denture markers have been that they should be biologically inert (when incorporated into the denture), not be expensive, be easy to inscribe, be possible to retrieve after an accident, and survive elevated temperatures for a reasonable time under normal circumstances. Although the frequency of edentulousness has decreased in recent years due to the improvement in oral health there remains a need to address the issue of marking of complete dentures, because there is a large variation in the oral status of populations in different countries. Given that only one marked denture can reveal the identity of a deceased person when all other methods fail to do so, makes it worthwhile. Furthermore, denture marking is important in long-term care facilities. We have investigated the issue of denture marking in Europe and in the United States. The results from the European survey show that denture marking is, to our knowledge regulated by law only in Sweden and Iceland. In the US denture marking is so far mandatory in 21 states while New York State requires dentures to be marked if the patient requests it and several other states impose the obligation to mark dentures on long-term care facilities. Since there is no international consensus regarding the issue of denture marking it is important to address it. A survey from the Nordic countries has shown that if denture marking was in general use, the contribution to the establishment of identity by forensic odontology in cases of fire would increase by about 10

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

PubMed

Kiersztan, Anna; Trojan, Nina; Tempes, Aleksandra; Nalepa, Paweł; Sitek, Joanna; Winiarska, Katarzyna; Usarek, Michał

2017-11-01

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes

Restricted growth of attenuated poliovirus strains in cultured cells of a human neuroblastoma.

PubMed

Agol, V I; Drozdov, S G; Ivannikova, T A; Kolesnikova, M S; Korolev, M B; Tolskaya, E A

1989-09-01

Cultured cells of a human neuroblastoma, SK-N-MC, were found to be highly resistant to Sabin attenuated poliovirus types 1 and 2 strains; no appreciable cytopathic effect was observed, and the total harvest was generally in the order of 1 PFU per cell or less. On the other hand, related neurovirulent strains of these antigenic types produced a relatively good (2 orders of magnitude higher) yield in a markedly protracted infectious cycle. The limited growth of the attenuated virus in the neuroblastoma cells appeared to be confined to a minor cell subpopulation. Experiments with intratypic (type 1) poliovirus recombinants suggested that the major genetic determinants limiting reproduction of the attenuated polioviruses in the neuroblastoma cells are located in the 5' half of the viral RNA, although the 3' half also appears to contribute somewhat to this phenotype. The possibility that neuroblastoma cells may represent an in vitro model for studying poliovirus neurovirulence is briefly discussed.

Hyperforin attenuates microglia activation and inhibits p65-Ser276 NFκB phosphorylation in the rat piriform cortex following status epilepticus.

PubMed

Lee, Sang-Kyu; Kim, Ji-Eun; Kim, Yeon-Joo; Kim, Min-Ju; Kang, Tae-Cheon

2014-08-01

Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has neurobiological effects including antidepressant activity, antibiotic potency, anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin activates transient receptor potential conical channel-6 (TRPC6), a nonselective cation channel. To elucidate the roles of hyperforin and TRPC6 in neuroinflammation in vivo, we investigated the effect of hyperforin on neuroinflammatory responses and its related events in the rat piriform cortex (PC) following status epilepticus (SE). Hyperforin attenuated microglial activation, p65-serine 276 NFκB phosphorylation, and suppressed TNF-α expression in the PC following SE. Hyperforin also effectively alleviated SE-induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction and blood-derived monocyte infiltration. Our findings suggest that hyperforin may effectively attenuate microglia-mediated neuroinflammation in the TRPC6-independent manner. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Fibronectin type III domain containing 5 attenuates NLRP3 inflammasome activation and phenotypic transformation of adventitial fibroblasts in spontaneously hypertensive rats.

PubMed

Ling, Li; Chen, Dan; Tong, Ying; Zang, Ying-Hao; Ren, Xing-Sheng; Zhou, Hong; Qi, Xiao-Hong; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2018-05-01

Phenotypic transformation of adventitial fibroblasts is important in the pathogenesis of hypertension. This study was designed to determine whether fibronectin type III domain containing 5 (FNDC5) alleviates the phenotypic transformation of adventitial fibroblasts in hypertension and the underlying mechanisms. Experiments were carried out in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and primary aortic adventitial fibroblasts. FNDC5 was downregulated and NLRP3 inflammasome was activated in aortic adventitia of SHR. FNDC5 overexpression attenuated adventitial fibroblasts phenotypic transformation, excessive synthesis and secretion of matrix components, NLRP3 inflammasome activation and inflammation in adventitial fibroblasts from SHR. Moreover, FNDC5 overexpression reduced NADPH oxidase 2 (NOX2) expression and reactive oxygen species (ROS) production in adventitial fibroblasts from SHR. Similarly, exogenous FNDC5 inhibited adventitial fibroblasts phenotypic transformation, expression of matrix components, NLRP3 inflammasome activation and NOX2 expression in adventitial fibroblasts from SHR. FNDC5 overexpression in rats attenuated phenotypic transformation, inflammation and reactive oxygen species (ROS) production in the aortic adventitia of SHR. Furthermore, FNDC5 overexpression reduced blood pressure and alleviated vascular remodeling in SHR. FNDC5 reduces NOX2-derived ROS production, NLRP3 inflammasome activation and phenotypic transformation in adventitial fibroblasts of SHR. FNDC5 plays a beneficial role in attenuating vascular inflammation, vascular remodeling and hypertension in SHR.

Relation between central adiposity and cognitive function in the Maine-Syracuse Study: attenuation by physical activity.

PubMed

Dore, Gregory A; Elias, Merrill F; Robbins, Michael A; Budge, Marc M; Elias, Penelope K

2008-06-01

Previous studies have demonstrated a relationship between central adiposity and cognitive function. However, only some of these studies have adjusted for cardiovascular risk factors and cardiovascular disease, and none have also adjusted for physical activity level. The purpose of the study was to examine the association between anthropometric measures of central adiposity (waist circumference and waist/hip ratio) and cognitive functioning with adjustment for cardiovascular disease risk factors and physical activity. Participants were 917 stroke- and dementia-free community-dwelling adults (59% women) in the Maine-Syracuse Study. The design was cross-sectional. Outcome measures included tests from the Wechsler Adult Intelligence Scale, the Halstead-Reitan Neuropsychological Battery, the Wechsler Memory Scale Revised, and the Mini-Mental State Examination. Waist circumference and waist/hip ratio were inversely related to multiple cognitive domains with adjustment for age, education, gender, and number of prior exams. For example, a 20-cm increment in waist circumference was associated with a 0.14 SD decrement in the Global Composite score. These relations were attenuated with adjustment for cardiovascular disease risk factors. However, with further adjustment for physical activity level, only waist circumference remained significantly associated with performance on the Similarities test. Waist circumference and waist/hip ratio are inversely related to cognitive function. Measures of central adiposity predict cognitive function independently of associated cardiovascular risk factors and events; however, the association between central adiposity and cognitive function is attenuated, to a large extent, by adjustment for physical activity level. Physical activity is an important covariate in studies relating measures of central adiposity to cognition.

Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity.

PubMed

Beagle, Brandon; Mi, Kaihong; Johnson, Gail V W

2009-11-01

The canonical Wnt/beta-catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3beta-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane-anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity. However, it is unknown if the ability of LRP6-ICD to attenuate GSK3beta activity and modulate activation of the Wnt/beta-catenin pathway requires phosphorylation of the LRP6-ICD PPP(S/T)P motifs, in a manner similar to the membrane-anchored LRP6 intracellular domain. Here we provide evidence that the LRP6-ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3beta to stabilize endogenous cytosolic beta-catenin resulting in activation of TCF/LEF-1 and the Wnt/beta-catenin pathway. LRP6-ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta-mediated phosphorylation of beta-catenin and tau to the same extent. These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6-ICD may be distinct from membrane-anchored LRP6, and that release of the LRP6-ICD may provide a complimentary signaling cascade capable of modulating Wnt-dependent gene expression. (c) 2009 Wiley-Liss, Inc.

Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise.

PubMed

Jia, Tiantian; Ogawa, Yoshiko; Miura, Misa; Ito, Osamu; Kohzuki, Masahiro

2016-01-01

Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise.

Seismic attenuation in the African LLSVP estimated from PcS phases

NASA Astrophysics Data System (ADS)

Liu, Chujie; Grand, Stephen P.

2018-05-01

Seismic tomography models have revealed two broad regions in the lowermost mantle marked by ∼3% slower shear velocity than normal beneath the south central Pacific and southern Africa. These two regions are known as large-low-shear-velocity provinces (LLSVP). There is debate over whether the LLSVPs can be explained by purely thermal variations or whether they must be chemically distinct from normal mantle. Elastic properties alone, have been unable to distinguish the thermal from chemical interpretations. Anelastic structure, however, can help discriminate among models of the LLSVPs since intrinsic attenuation is more sensitive to temperature than to chemical variations. Here we estimate Qμ (the shear wave quality factor) in the African LLSVP using PcS waves generated from a Scotia Arc earthquake, recorded by broadband seismometers deployed in Southern Africa during the Kaapvaal experiment. The upward leg of the PcS waves sweeps from normal mantle into the African LLSVP across the array. We use the spectral ratio (SR) and instantaneous frequency matching (IFM) techniques to measure the differential attenuation (Δt*) between waves sampling the African LLSVP and the waves that sample normal lower mantle. Using both methods for estimating Δt* we find that PcS waves sampling the LLSVP are more attenuated than the waves that miss the LLSVP yielding a Δt* difference of more than 1 s. Using the Δt* measurements we estimate the average Qμ in the LLSVP to be about 110. Using a range of activation enthalpy (H*) estimates, we find an average temperature anomaly within the LLSVP ranging from +250 to +800 K. Our estimated temperature anomaly range overlaps previous isochemical geodynamic studies that explain the LLSVP as a purely thermal structure although the large uncertainties cannot rule out chemical variations as well.

Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis.

PubMed

Li, Naisi; Yang, Qiyuan; Walker, Ryan G; Thompson, Thomas B; Du, Min; Rodgers, Buel D

2016-01-01

A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.

Adenosine monophosphate-activated protein kinase attenuates cardiomyocyte hypertrophy through regulation of FOXO3a/MAFbx signaling pathway.

PubMed

Chen, Baolin; Wu, Qiang; Xiong, Zhaojun; Ma, Yuedong; Yu, Sha; Chen, Dandan; Huang, Shengwen; Dong, Yugang

2016-09-01

Control of cardiac muscle mass is thought to be determined by a dynamic balance of protein synthesis and degradation. Recent studies have demonstrated that atrophy-related forkhead box O 3a (FOXO3a)/muscle atrophy F-box (MAFbx) signaling pathway plays a central role in the modulation of proteolysis and exert inhibitory effect on cardiomyocyte hypertrophy. In this study, we tested the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation attenuates cardiomyocyte hypertrophy by regulating FOXO3a/MAFbx signaling pathway and its downstream protein degradation. The results showed that activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) attenuated cardiomyocyte hypertrophy induced by angiotensin II (Ang II). The antihypertrophic effects of AICAR were blunted by AMPK inhibitor Compound C. In addition, AMPK dramatically increased the activity of transcription factor FOXO3a, up-regulated the expression of its downstream ubiquitin ligase MAFbx, and enhanced cardiomyocyte proteolysis. Meanwhile, the effects of AMPK on protein degradation and cardiomyocyte hypertrophy were blocked after MAFbx was silenced by transfection of cardiomyocytes with MAFbx-siRNA. These results indicate that AMPK plays an important role in the inhibition of cardiomyocyte hypertrophy by activating protein degradation via FOXO3a/MAFbx signaling pathway. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

4-Hydroxy TEMPO attenuates dichlorvos induced microglial activation and apoptosis.

PubMed

Sunkaria, Aditya; Sharma, Deep Raj; Wani, Willayat Yousuf; Gill, Kiran Dip

2014-02-19

Microglial cells have been implicated in various neurodegenerative diseases. Previous studies from our lab have shown that dichlorvos (an organophosphate) could induce Parkinson's like features in rats. Recently, we have shown that dichlorvos can induce microglial activation, and if not checked in time could ultimately induce neuronal apoptosis. However, this activation does not always pose a threat to the neurons. Activated microglia also secrete various neuronal growth factors, suggesting that they have beneficial roles in CNS repair. Therefore, it is essential to control their detrimental functions selectively. Here, we tried to find out how microglial cells behave when exposed to dichlorvos in either the presence or absence of potent nitric oxide scavenger and superoxide dismutase mimetic, 4-hydroxy TEMPO (4-HT). Wistar rat pups (1 day) were used to isolate and culture primary microglial cells. We found 4-HT pretreatment successfully attenuated the dichlorvos mediated microglial activation. Moreover, 4-HT pretreatment decreased the up-regulated levels of p53 and its downstream effector, p21. The expression of various cell cycle regulators such as Chk2, CDC25a, and cyclin A remained close to their basal levels when 4-HT pretreatment was given. DNA fragmentation analysis showed significant reduction in the DNA damage of 4-HT pretreated microglia as compared to dichlorvos treated cells. In addition to this, we found 4-HT pretreatment prevented the microglial cells from undergoing apoptotic cell death even after 48 h of dichlorvos exposure. Taken together, our results showed 4-HT pretreatment could successfully ameliorate the dichlorvos induced microglial cell damage.

Light attenuation characteristics of glacially-fed lakes

NASA Astrophysics Data System (ADS)

Rose, Kevin C.; Hamilton, David P.; Williamson, Craig E.; McBride, Chris G.; Fischer, Janet M.; Olson, Mark H.; Saros, Jasmine E.; Allan, Mathew G.; Cabrol, Nathalie

2014-07-01

Transparency is a fundamental characteristic of aquatic ecosystems and is highly responsive to changes in climate and land use. The transparency of glacially-fed lakes may be a particularly sensitive sentinel characteristic of these changes. However, little is known about the relative contributions of glacial flour versus other factors affecting light attenuation in these lakes. We sampled 18 glacially-fed lakes in Chile, New Zealand, and the U.S. and Canadian Rocky Mountains to characterize how dissolved absorption, algal biomass (approximated by chlorophyll a), water, and glacial flour contributed to attenuation of ultraviolet radiation (UVR) and photosynthetically active radiation (PAR, 400-700 nm). Variation in attenuation across lakes was related to turbidity, which we used as a proxy for the concentration of glacial flour. Turbidity-specific diffuse attenuation coefficients increased with decreasing wavelength and distance from glaciers. Regional differences in turbidity-specific diffuse attenuation coefficients were observed in short UVR wavelengths (305 and 320 nm) but not at longer UVR wavelengths (380 nm) or PAR. Dissolved absorption coefficients, which are closely correlated with diffuse attenuation coefficients in most non-glacially-fed lakes, represented only about one quarter of diffuse attenuation coefficients in study lakes here, whereas glacial flour contributed about two thirds across UVR and PAR. Understanding the optical characteristics of substances that regulate light attenuation in glacially-fed lakes will help elucidate the signals that these systems provide of broader environmental changes and forecast the effects of climate change on these aquatic ecosystems.

Anatomy of a caldera: seismic velocity and attenuation models of the Campi Flegrei (Italy).

NASA Astrophysics Data System (ADS)

Calò, Marco; Tramelli, Anna

2017-04-01

Campi Flegrei is an active Caldera marked by strong vertical deformations of the soil called bradyseisms. The mechanisms proposed to explain this phenomenon are essentially three i) the presence of a shallow magmatic chamber that pushes the lid and consequently producing periodic variation of the soil level, ii) a thermic expansion of the geothermal aquifer due to the periodic increase of heat flux coming from a near magmatic chamber or deep fluids or iii) a combination of both phenomena. To solve the paradox, several models have been proposed to describe the nature and the geometry of the bodies responsible of the bradyseisms. Seismological tools allowed a rough description of the main features in terms of seismic velocities and attenuation parameters and till now were not able to resolve the smallest structures (<1.5-2km) located at shallow depth (0-4 km) and believed to be responsible of the soil deformations. Here we show Vp, Vp/Vs and Qp models carried out by applying an enhanced seismic tomography method combining the double difference approach (Zhang and Thurber, 2003) and the Weighted Average Method (Calò et al., 2009, Calò et al., 2011, 2013). The data used are the earthquakes recorded during the largest bradyseism crisis of the 80's. Our method allowed to image seismic velocity and attenuation structures with linear dimension of 0.5-1.2km, resulting in an improvement of the resolving power at least two times of the other published models (e.g. Priolo et al., 2012). The joint interpretation of seismic velocities and attenuation models allowed to discern small anomalous bodies at shallow depth (0.5-2.0 km) marked by relatively low Vp, high Vp/Vs ratio and low Qp values explainable with the presence of shallow geothermal water saturated reservoir from regions with low Vp, low Vp/Vs and low Qp possibly related to the gas saturated part of the reservoir. At deeper depth (2-3.5 km) bodies with high Vp and Vp/Vs and low Qp can be associated with magmatic

Arctigenin but not arctiin acts as the major effective constituent of Arctium lappa L. fruit for attenuating colonic inflammatory response induced by dextran sulfate sodium in mice.

PubMed

Wu, Xin; Yang, Yan; Dou, Yannong; Ye, Jun; Bian, Difei; Wei, Zhifeng; Tong, Bei; Kong, Lingyi; Xia, Yufeng; Dai, Yue

2014-12-01

The crude powder of the fruit of Arctium lappa L. (ALF) has previously been reported to attenuate experimental colitis in mice. But, its main effective ingredient and underlying mechanisms remain to be identified. In this study, ALF was extracted with ethanol, and then successively fractionated into petroleum ether, ethyl acetate, n-butanol and water fraction. Experimental colitis was induced by dextran sulfate sodium (DSS) in mice. Among the four fractions of ALF, the ethyl acetate fraction showed the most significant inhibition of DSS-induced colitis in mice. The comparative studies of arctigenin and arctiin (the two main ingredients of ethyl acetate fraction) indicated that arctigenin rather than arctiin could reduce the loss of body weight, disease activity index and histological damage in the colon. Arctigenin markedly recovered the loss of intestinal epithelial cells (E-cadherin-positive cells) and decreased the infiltration of neutrophils (MPO-positive cells) and macrophages (CD68-positive cells). Arctigenin could down-regulate the expressions of TNF-α, IL-6, MIP-2, MCP-1, MAdCAM-1, ICAM-1 and VCAM-1 at both protein and mRNA levels in colonic tissues. Also, it markedly decreased the MDA level, but increased SOD activity and the GSH level. Of note, the efficacy of arctigenin was comparable or even superior to that of the positive control mesalazine. Moreover, it significantly suppressed the phosphorylation of MAPKs and the activation of NF-κB, including phosphorylation of IκBα and p65, p65 translocation and DNA binding activity. In conclusion, arctigenin but not arctiin is the main active ingredient of ALF for attenuating colitis via down-regulating the activation of MAPK and NF-κB pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

Leptin attenuates BACE1 expression and Amyloid-β genesis via the activation of SIRT1 signaling pathway

PubMed Central

Marwarha, Gurdeep; Raza, Shaneabbas; Meiers, Craig; Ghribi, Othman

2014-01-01

The aspartyl protease β-site AβPP-cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in Aβ production, a peptide at the nexus of neurodegenerative cascades in Alzheimer Disease (AD). The adipocytokine leptin has been demonstrated to reduce Aβ production and decrease BACE1 activity and expression levels. However, the signaling cascades involved in the leptin-induced mitigation in Aβ levels and BACE1 expression levels have not been elucidated. We have demonstrated that the transcription factor nuclear factor – kappa B (NF-κB) positively regulates BACE1 transcription. NF-κB activity is tightly regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced that leptin activates the metabolic master regulator SIRT1. In this study, we determined the extent to which SIRT1 expression and activity regulate the leptin-induced attenuation in BACE1 expression and Aβ levels in cultured human neuroblastoma SH-SY5Y cells. This study also elucidated and delineated the signal transduction pathways involved in the leptin induced mitigation in BACE1 expression. Our results demonstrate for the first time that leptin attenuates the activation and transcriptional activity of NF-κB by reducing the acetylation of the p65 subunit in a SIRT1-dependent manner. Furthermore, our data shows that leptin reduces the NF-κB – mediated transcription of BACE1 and consequently reduces Amyloid-β genesis. Our study provides a valuable insight and a novel mechanism by which leptin reduces BACE1 expression and Amyloid-β production and may help design potential therapeutic interventions. PMID:24874077

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

PubMed Central

Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

2015-01-01

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study.

PubMed

Celis-Morales, Carlos; Marsaux, Cyril F M; Livingstone, Katherine M; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; O'donovan, Clare B; Forster, Hannah; Woolhead, Clara; Fallaize, Rosalind; Macready, Anna L; Kolossa, Silvia; Hallmann, Jacqueline; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Parnell, Laurence D; Daniel, Hannelore; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Gibney, Mike; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim H M; Mathers, John C

2016-04-01

To examine whether the effect of FTO loci on obesity-related traits could be modified by physical activity (PA) levels in European adults. Of 1,607 Food4Me participants randomized, 1,280 were genotyped for FTO (rs9939609) and had available PA data. PA was measured objectively using accelerometers (TracmorD, Philips), whereas anthropometric measures [BMI and waist circumference (WC)] were self-reported via the Internet. FTO genotype was associated with a higher body weight [β: 1.09 kg per risk allele, (95% CI: 0.14-2.04), P = 0.024], BMI [β: 0.54 kg m(-2) , (0.23-0.83), P < 0.0001], and WC [β: 1.07 cm, (0.24-1.90), P = 0.011]. Moderate-equivalent PA attenuated the effect of FTO on BMI (P[interaction]  = 0.020). Among inactive individuals, FTO increased BMI by 1.06 kg m(-2) per allele (P = 0.024), whereas the increase in BMI was substantially attenuated among active individuals (0.16 kg m(-2) , P = 0.388). We observed similar effects for WC (P[interaction]  = 0.005): the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals. PA attenuates the effect of FTO genotype on BMI and WC. This may have important public health implications because genetic susceptibility to obesity in the presence of FTO variants may be reduced by adopting a physically active lifestyle. © 2016 The Obesity Society.

Stretch marks

MedlinePlus

Stretch marks can appear when there is rapid stretching of the skin. The marks appear as parallel ... often disappear after the cause of the skin stretching is gone. Avoiding rapid weight gain helps reduce ...

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells.

PubMed

Genz, Berit; Thomas, Maria; Pützer, Brigitte M; Siatkowski, Marcin; Fuellen, Georg; Vollmar, Brigitte; Abshagen, Kerstin

2014-11-01

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. Copyright © 2014 Elsevier Inc. All rights reserved.

Short-term high-intensity interval exercise training attenuates oxidative stress responses and improves antioxidant status in healthy humans.

PubMed

Bogdanis, G C; Stavrinou, P; Fatouros, I G; Philippou, A; Chatzinikolaou, A; Draganidis, D; Ermidis, G; Maridaki, M

2013-11-01

This study investigated the changes in oxidative stress biomarkers and antioxidant status indices caused by a 3-week high-intensity interval training (HIT) regimen. Eight physically active males performed three HIT sessions/week over 3 weeks. Each session included four to six 30-s bouts of high-intensity cycling separated by 4 min of recovery. Before training, acute exercise elevated protein carbonyls (PC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC) and creatine kinase (CK), which peaked 24h post-exercise (252 ± 30%, 135 ± 17%, 10 ± 2%, 85 ± 14% and 36 ± 13%, above baseline, respectively; p<0.01), while catalase activity (CAT) peaked 30 min post-exercise (56 ± 18% above baseline; p<0.01). Training attenuated the exercise-induced increase in oxidative stress markers (PC by 13.3 ± 3.7%; TBARS by 7.2 ± 2.7%, p<0.01) and CK activity, despite the fact that total work done was 10.9 ± 3.6% greater in the post- compared with the pre-training exercise test. Training also induced a marked elevation of antioxidant status indices (TAC by 38.4 ± 7.2%; CAT by 26.2 ± 10.1%; GPX by 3.0 ± 0.6%, p<0.01). Short-term HIT attenuates oxidative stress and up-regulates antioxidant activity after only nine training sessions totaling 22 min of high intensity exercise, further supporting its positive effect not only on physical conditioning but also on health promotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

Activation of peroxisome proliferator-activated receptor δ inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells.

PubMed

Ham, Sun Ah; Lee, Hanna; Hwang, Jung Seok; Kang, Eun Sil; Yoo, Taesik; Paek, Kyung Shin; Do, Jeong Tae; Park, Chankyu; Oh, Jae-Wook; Kim, Jin-Hoi; Han, Chang Woo; Seo, Han Geuk

2014-01-01

We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARδ, indicating that the effects of GW501516 are PPARδ dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3-kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP-2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARδ confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells. © 2014 S. Karger AG, Basel.

Stretch Marks

MedlinePlus

... stretch marks. This isn't true with regular tanning or tanning beds , though: Stretch marks are less likely to ... up looking more obvious. Plus, the sun and tanning beds do more harm than good when it ...

Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis

PubMed Central

Li, Naisi; Yang, Qiyuan; Walker, Ryan G.; Thompson, Thomas B.; Du, Min

2016-01-01

A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn−/− (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn−/− BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn−/− animals results from nutrient partitioning away from fat and in support of muscle. PMID:26580671

Pavement markings and safety.

DOT National Transportation Integrated Search

2010-11-01

Previous research on pavement markings from a safety perspective tackled various issues such as pavement marking retroreflectivity : variability, relationship between pavement marking retroreflectivity and driver visibility, or pavement marking impro...

Phosphodiesterase 5 Inhibition Attenuates Cerebral Vasospasm and Improves Functional Recovery after Experimental Subarachnoid Hemorrhage

PubMed Central

Han, Byung Hee; Vellimana, Ananth Kesav; Zhou, Meng-Liang; Milner, Eric; Zipfel, Gregory Joseph

2014-01-01

Background Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic GMP (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5) – an enzyme that degrades cGMP – may play a role, as the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. Objective To elucidate the mechanism of action of sildenafil against vasospasm, and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. Methods SAH was induced via endovascular perforation in male C57BL6 mice. Beginning two hours later, mice received sildenafil citrate (0.7, 2 or 5mg/kg P.O. BID) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH Day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure (BP), and intracranial pressure (ICP) were examined. Results We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to reduce vasospasm, decrease neuronal cell death, and markedly improve neurological outcome, without causing significant physiological side effects. Conclusion Sildenafil–an FDA-approved drug with a proven track record of safety in humans –is a promising new therapy for vasospasm and neurological deficits following SAH. PMID:21796010

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein.

PubMed

Li, Zhijuan; Cheng, Jianxin; Wang, Liping

2015-10-30

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. Copyright © 2015. Published by Elsevier Inc.

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic range neuronal activity in rats

PubMed Central

Yang, Fei; Zhang, Chen; Xu, Qian; Tiwari, Vinod; He, Shao-Qiu; Wang, Yun; Dong, Xinzhong; Vera-Portocarrero, Louis P.; Wacnik, Paul W.; Raja, Srinivasa N.; Guan, Yun

2014-01-01

Objectives Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. Materials and Methods We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 ms, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). Results The elevated spontaneous activity rate of WDR neurons in SNL rats [n=25; data combined from day 14–16 (n = 15) and day 45–75 post-SNL groups (n=10)] was significantly decreased from the pre-stimulation level (p<0.01) at 0–15 min and 30–45 min post-stimulation. In both sham-operated (n=8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1–10 mA, 2 ms) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a short form of neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0–15 min in all groups (p<0.05). Conclusions Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain. PMID:25308522

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

PubMed

Flynn, Padrig B; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P; Elliott, Christopher T; Laverty, Garry; Gorman, Sean P; Graham, William G; Gilmore, Brendan F

2016-05-31

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30-60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence

PubMed Central

Flynn, Padrig B.; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P.; Elliott, Christopher T.; Laverty, Garry; Gorman, Sean P.; Graham, William G.; Gilmore, Brendan F.

2016-01-01

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa. PMID:27242335

Leptin attenuates BACE1 expression and amyloid-β genesis via the activation of SIRT1 signaling pathway.

PubMed

Marwarha, Gurdeep; Raza, Shaneabbas; Meiers, Craig; Ghribi, Othman

2014-09-01

The aspartyl protease β-site AβPP-cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in Aβ production, a peptide at the nexus of neurodegenerative cascades in Alzheimer Disease (AD). The adipocytokine leptin has been demonstrated to reduce Aβ production and decrease BACE1 activity and expression levels. However, the signaling cascades involved in the leptin-induced mitigation in Aβ levels and BACE1 expression levels have not been elucidated. We have demonstrated that the transcription factor nuclear factor - kappa B (NF-κB) positively regulates BACE1 transcription. NF-κB activity is tightly regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced that leptin activates the metabolic master regulator SIRT1. In this study, we determined the extent to which SIRT1 expression and activity regulate the leptin-induced attenuation in BACE1 expression and Aβ levels in cultured human neuroblastoma SH-SY5Y cells. This study also elucidated and delineated the signal transduction pathways involved in the leptin induced mitigation in BACE1 expression. Our results demonstrate for the first time that leptin attenuates the activation and transcriptional activity of NF-κB by reducing the acetylation of the p65 subunit in a SIRT1-dependent manner. Furthermore, our data shows that leptin reduces the NF-κB-mediated transcription of BACE1 and consequently reduces Amyloid-β genesis. Our study provides a valuable insight and a novel mechanism by which leptin reduces BACE1 expression and Amyloid-β production and may help design potential therapeutic interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

Mice with cancer-induced bone pain show a marked decline in day/night activity.

PubMed

Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W

2017-09-01

Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

PubMed

Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

2017-07-18

Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation

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

Kim, Sang-pil; Ha, Jung Min; Yun, Sung Ji

2010-08-13

Research highlights: {yields} Elevated cAMP activates both PKA and Epac. {yields} PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. {yields} Akt modulates PPAR-{gamma} transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-{gamma} is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-{gamma}. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by amore » Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-{gamma} was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-{gamma} transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-{gamma} transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-{gamma}, suggesting post-translational activation of PPAR-{gamma} might be critical step for adipogenic gene expression.« less

Curcumin Attenuated Bupivacaine-Induced Neurotoxicity in SH-SY5Y Cells Via Activation of the Akt Signaling Pathway.

PubMed

Fan, You-Ling; Li, Heng-Chang; Zhao, Wei; Peng, Hui-Hua; Huang, Fang; Jiang, Wei-Hang; Xu, Shi-Yuan

2016-09-01

Bupivacaine is widely used for regional anesthesia, spinal anesthesia, and pain management. However, bupivacaine could cause neuronal injury. Curcumin, a low molecular weight polyphenol, has a variety of bioactivities and may exert neuroprotective effects against damage induced by some stimuli. In the present study, we tested whether curcumin could attenuate bupivacaine-induced neurotoxicity in SH-SY5Y cells. Cell injury was evaluated by examining cell viability, mitochondrial damage and apoptosis. We also investigated the levels of activation of the Akt signaling pathway and the effect of Akt inhibition by triciribine on cell injury following bupivacaine and curcumin treatment. Our findings showed that the bupivacaine treatment could induce neurotoxicity. Pretreatment of the SH-SY5Y cells with curcumin significantly attenuated bupivacaine-induced neurotoxicity. Interestingly, the curcumin treatment increased the levels of Akt phosphorylation. More significantly, the pharmacological inhibition of Akt abolished the cytoprotective effect of curcumin against bupivacaine-induced cell injury. Our data suggest that pretreating SH-SY5Y cells with curcumin provides a protective effect on bupivacaine-induced neuronal injury via activation of the Akt signaling pathway.

Marking nut anaphylaxis

PubMed Central

Kral, Anita Christine; Hayball, John; Smith, William B

2016-01-01

Marking nut Semecarpus anacardium, so-called because it contains a pigment that has been used in the past to mark fabrics, is a known cause of contact hypersensitivity. It may be ingested as an ingredient of some traditional Hindi foods. We describe the first reported case of anaphylaxis to marking nut. PMID:27489793

Mark Mehos | NREL

Science.gov Websites

Mehos Photo of Mark Mehos Mark Mehos Group Manager, Thermal Systems R&D Mark.Mehos@nrel.gov Thermal Systems R&D group at NREL, which includes the Concentrating Solar Power (CSP) Program. Since SolarPACES "Solar Thermal Electric Power Systems" task, which focuses on the development of

Pyrrolidine Dithiocarbamate Attenuates Paraquat-Induced Lung Injury in Rats

PubMed Central

Chang, Xiuli; Shao, Chunfeng; Wu, Qing; Wu, Qiangen; Huang, Min; Zhou, Zhijun

2009-01-01

Paraquat (PQ) has been demonstrated that the main target organ for the toxicity is the lung. This study aimed to investigate the potential protective effect of PDTC on the PQ-induced pulmonary damage. Fifty-four rats were divided into control, PQ-treated and PQ+PDTC-treated groups. Rats in the PQ group were administrated 40 mg/kg PQ by gastric gavage, and PDTC group with 40 mg/kg PQ followed by injection of 120 mg/kg PDTC (IP). On the days 3, 7, 14 and 21 after treatments, the activities of GSH-Px, SOD, MDA level and the content of HYP were measured. TGF-β1 mRNA and protein were assayed by RT-PCR and ELISA. MDA level in plasma and BALF was increased and the activities of GSH-Px and SOD were decreased significantly in the PQ-treated groups (P < .05) compared with control group. While the activities of GSH-Px and SOD in the PQ+PDTC-treated groups was markedly higher than that of PQ-treated groups (P < .05), and in contrast, MDA level was lower. TGF-β1 mRNA and protein were significantly lower in the PQ+PDTC-treated groups than that of PQ-treated groups (P < .05). The histopathological changes in the PQ+PDTC-treated groups were milder than those of PQ groups. Our results suggested that PDTC treatment significantly attenuated paraquat-induced pulmonary damage. PMID:19639047

CD28/B7 deficiency attenuates systolic overload-induced congestive heart failure, myocardial and pulmonary inflammation, and activated T-cell accumulation in the heart and lungs

PubMed Central

Wang, Huan; Kwak, Dongmin; Fassett, John; Hou, Lei; Xu, Xin; Burbach, Brandon J.; Thenappan, Thenappan; Xu, Yawei; Ge, Jun-bo; Shimizu, Yoji; Bache, Robert J.; Chen, Yingjie

2017-01-01

The inflammatory response regulates congestive heart failure (CHF) development. T-cell activation plays an important role in tissue inflammation. We postulate that CD28 or B7 deficiency inhibits T-cell activation and attenuates CHF development by reducing systemic, cardiac and pulmonary inflammation. We demonstrated that chronic pressure overload-induced end-stage CHF in mice is characterized by profound accumulation of activated effector T-cells (CD3+CD44high cells) in the lungs and a mild but significant increase of these cells in the heart. In knockout (KO) mice lacking either CD28 or B7, there was a dramatic reduction in the accumulation of activated effector T cells in both hearts and lungs of mice under control conditions and after transverse aortic constriction (TAC). CD28 or B7 KO significantly attenuated TAC-induced CHF development, as indicated by less increase of heart and lung weight, and less reduction of LV contractility. CD28 or B7 KO also significantly reduced TAC-induced CD45+ leukocyte, T-cell and macrophage infiltration in hearts and lungs, lowered pro-inflammatory cytokine expression (such as TNF-α and IL-1β) in lungs. Furthermore, CD28/B7 blockade by CTLA4-Ig treatment (250μg/mouse every 3 days) attenuated TAC-induced T cell activation, LV hypertrophy, and LV dysfunction. Our data indicate that CD28/B7 deficiency inhibits activated effector T-cell accumulation, reduces myocardial and pulmonary inflammation, and attenuates the development of CHF. Our findings suggest that strategies targeting T-cell activation may be useful in treating CHF. PMID:27432861

Leaving A Mark: A Comparison Arthropod Protein Marking Protocols

USDA-ARS?s Scientific Manuscript database

Knowledge of arthropod pest and natural enemy disperal patterns is needed for effective and environmentally benign pest control. The most common tactics used to monitor arthropod dispersal patterns include mark-release-recapture (MRR) and mark-capture methodologies. Both methods require the applica...

Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice.

PubMed

Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E; Moorthy, Bhagavatula

2015-11-01

Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mastering Marking Madness

ERIC Educational Resources Information Center

Moore, Brooke

2009-01-01

Teachers are smart people, so why does marking reduce them to stressed and soulless messes? Because in their hearts they know that students do not learn from it, and that drives them nuts. Researchers like Lorna Earl and Dylan Wiliam have looked closely at marking systems and have proven what teachers already know deep down: marking student work…

MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

PubMed

Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

2018-04-15

MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

PubMed

Yang, Yang; Duan, Weixun; Lin, Yan; Yi, Wei; Liang, Zhenxing; Yan, Juanjuan; Wang, Ning; Deng, Chao; Zhang, Song; Li, Yue; Chen, Wensheng; Yu, Shiqiang; Yi, Dinghua; Jin, Zhenxiao

2013-12-01

Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling. © 2013 Elsevier Inc. All rights reserved.

A novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator RS9 attenuates brain injury after ischemia reperfusion in mice.

PubMed

Yamauchi, Keita; Nakano, Yusuke; Imai, Takahiko; Takagi, Toshinori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Iwama, Toru; Hara, Hideaki

2016-10-01

Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique. RS9 has been reported to lead to higher Nrf2 activation and less cytotoxicity than BARD. In this study, we investigated the effects of RS9 on IRI. Mice were intraperitoneally treated immediately after 2h of transient middle cerebral artery occlusion (MCAO) with a vehicle solution or 0.2mg/kg of RS9. Post-onset treatment of RS9 attenuated the infarct volume and improved neurological deficits 22h after reperfusion. RS9 activated Nrf2 2 and 6h after reperfusion and activated heme oxygenase-1 at 6 and 22h after reperfusion. RS9 also attenuated the phosphorylation of NF-κB p65 2 and 6h after reperfusion. Finally, RS9 improved the survival rate and neurological deficits 7days after MCAO. Our results suggest that the activation of Nrf2 by RS9 has a neuroprotective effect, mediated by attenuating both oxidative stress and neuroinflammation, and that RS9 is an effective therapeutic candidate for the treatment of IRI. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

DCPIB, a potent volume-regulated anion channel antagonist, attenuates microglia-mediated inflammatory response and neuronal injury following focal cerebral ischemia.

PubMed

Han, Qingdong; Liu, Shengwen; Li, Zhengwei; Hu, Feng; Zhang, Qiang; Zhou, Min; Chen, Jingcao; Lei, Ting; Zhang, Huaqiu

2014-01-13

Accumulating evidence indicates that extensive microglia activation-mediated local inflammation contributes to neuronal injury in cerebral ischemia. We have previously shown that 4-(2-butyl-6, 7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), a potent volume-regulated anion channel (VRAC) inhibitor, suppresses pathological glutamate release and excitatory neurotoxicity in reversible middle cerebral artery occlusion (rMCAO) model in vivo. In the present study, we sought to determine whether DCPIB also attenuates microglia activation that could contribute to neuronal injury in the cerebral ischemia/reperfusion pathology. We show that oxygen-glucose deprivation (OGD) induced microglia proliferation, migration, and secretion of cytokines and all these pathological changes were effectively inhibited by DCPIB in vitro. In the microglia/neuron co-cultures, OGD induced neuronal damage was reduced markedly in the presence of DCPIB. In rat rMCAO animal model, DCPIB significantly attenuated microglia activation and neuronal death. Activation of mitogen-activated protein kinase (MAPK) signaling pathway is known to be a critical signaling pathway for microglia activation. We further explored a potential involvement of DCPIB in this pathway by western blot analysis. Under the conditions that MAPK pathway was activated either by lipopolysaccharides (LPS) or OGD, the levels of phosphorylated ERK1/2, JNK and p38 were reduced significantly in the presence of DCPIB. Altogether, our study demonstrated that DCPIB inhibits microglia activation potently under ischemic conditions both in vitro and in vivo. The DCPIB effect is likely attributable to both direct inhibition VRAC and indirect inhibition of MAPK pathway in microglia that are beneficial for the survival of neurons in cerebral ischemic conditions. © 2013 Elsevier B.V. All rights reserved.

[The scent marking of territory of gerbils: a comparative analysis exemplified by 4 species of the genus Meriones].

PubMed

Gromov, V S

1997-01-01

Sex-age and seasonal variability of the ventral glands and different stereotypes of scent marking behaviour in four Meriones species (M. unguiculatus, M. meridianus, M. libycus, M. tamariscinus) have been studied in nature and under semi-natural conditions. Two major ways of olfactory marking are considered: by secretion of the ventral glands and by "signal heaps" with urine and feces. Intraspecific and inter-species variability of marking activity is investigated. The ventral glands start to function at the period of preparation of a generative system to reproduction. The peak of secretary activity of gland and maximum of two types of marking activity is observed in spring and early summer, i.e. the period of active reproduction. The maximum of two types of the marking activity is observed during this period. In M. tamariscinus and M. meridianus the marking by the ventral gland is prevailing mode of the territory scent marking, while Mongolian gerbils (M. unguiculatus) prefer to use "signal heaps" Libyan gerbils (M. libycus) in this relation take an intermediate position. At the non-productive period a level of marking activity is on 10-20 times lower than at the reproductive season. Besides hormonal, social factors were also important for regulation of marking activity. By influence of these factors the differences in the level of marking activity in high-rank and low-rank individuals and differences in patterns of a spatial distribution of scent marks in individuals of different hierarchical rank is explained. Functional significance of various ways of territory scent marking is discussed.

Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone

PubMed Central

Cui, Zhuang; Crane, Janet; Xie, Hui; Jin, Xin; Zhen, Gehua; Li, Changjun; Xie, Liang; Wang, Long; Bian, Qin; Qiu, Tao; Wan, Mei; Xie, Min; Ding, Sheng; Yu, Bin; Cao, Xu

2016-01-01

Objectives Examine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models. Methods 3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone. Results Halofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone. Conclusions Halofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA

JIP3 deficiency attenuates cardiac hypertrophy by suppression of JNK pathway.

PubMed

Ma, Qinghua; Liu, Yuxiu; Chen, Lianghua

2018-06-15

Pathological cardiac hypertrophy is a leading cause of morbidity and mortality worldwide; however, our understanding of the molecular mechanisms revealing the disease is still unclear. In the present study, we suggested that c-Jun N-terminal kinase (JNK)-interacting protein 3 (JIP3), involved in various cellular processes, played an essential role in regulating pathological cardiac hypertrophy through in vivo and in vitro studies. JIP3 was highly expressed in human hearts with hypertrophic cardiomyopathy (HCM), and in mouse hypertrophic hearts. Following, the wild type (WT) and JIP3-knockout (KO) mice subjected to aortic banding (AB) challenge were used as animal models with cardiac hypertrophy. The results showed that JIP3-KO mice after AB operation exhibited attenuated cardiac function, reduced fibrosis levels and decreased hypertrophic marker proteins, including atrial natriuretic peptides (Anp) and brain/B-type natriuretic peptides (Bnp) and β-myosin heavy chain (β-Mhc). Loss of JIP3 also ameliorated oxidative stress, inflammatory response, apoptosis and endoplasmic reticulum (ER) stress in hearts of mice after AB surgery. Consistently, the expressions of ER stress-related molecules, such as phosphorylated-α-subunit of the eukaryotic initiation factor-2 (eIF2α), glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP), were markedly decreased by JIP3-deficiency in hearts of AB-operated mice. JNK and its down-streaming signal of p90rsk was highly activated by AB operation in WT mice, while being significantly reversed by JIP3-ablation. Intriguingly, the in vitro results showed that promoting JNK activation by using its activator of anisomycin enhanced AngII-stimulated ER stress, oxidative stress, apoptosis and inflammatory response in cardiomyocytes isolated from WT mice. However, JIP3-KO-attenuated these pathologies was rescued by anisomycin treatment in AngII-incubated cardiomyocytes. Together, the findings indicated that blockage of JIP3

Valproic acid treatment attenuates caspase-3 activation and improves survival after lethal burn injury in a rodent model.

PubMed

Luo, Hong-Min; Hu, Sen; Bai, Hui-Ying; Wang, Hai-Bin; Du, Ming-Hua; Lin, Zhi-Long; Ma, Li; Wang, Huan; Lv, Yi; Sheng, Zhi-Yong

2014-01-01

Burn injury may result in multiple organ dysfunction partially because of apoptotic cell death. The authors have previously shown that valproic acid (VPA) improves survival in a dog burn model. The aim of this study is to examine whether a VPA improves survival in a rodent burn model and whether this was because of inhibition of cell apoptosis. Rats were subjected to third-degree 55% TBSA burns and randomized to treatment with a VPA (300 mg/kg) or normal saline. One group of animals was monitored for 12 hours for survival analysis; another group was killed at 6 hours after injury, and brains, hearts, and blood samples were harvested for examination. Plasma creatine kinase (CK)-MB activities and neuron-specific enolase (NSE) levels were measured to evaluate the cardiac and brain damages. The effects of a VPA on acetylation of histone H3 and caspase-3 activation were also evaluated. Major burn injury resulted in a significant decrease in the acetylation of histone H3, and there was an increase in plasma CK-MB activities, NSE concentrations, and tissue levels of activated caspase-3. A VPA treatment significantly increased the acetylation of histone H3 and survival of the animals after major burn injury. In addition, a VPA treatment significantly attenuated the plasma CK-MB activities, an NSE concentrations, and inhibited caspase-3 activation after major burn injury. These results indicate that a VPA can attenuate cardiac and brain injury, and can improve survival in a rodent model of lethal burn injury. These protective effects may be mediated in part through the inhibition of caspase-3 activation.

Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light-induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF-κB suppression.

PubMed

Wang, Yong; Huo, Yazhen; Zhao, Liang; Lu, Feng; Wang, Ou; Yang, Xue; Ji, Baoping; Zhou, Feng

2016-07-01

Cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and a potential nutritional supplement for preventing retinal degeneration. However, the protective mechanism of C3G and its metabolites, protocatechuic acid (PCA) and ferulic acid (FA), remain unclear. The molecular mechanisms of C3G and its metabolites against retinal photooxidative damage in vivo are investigated. Pigmented rabbits were orally administered C3G, PCA, and FA (0.11 mmol/kg/day) for 3 weeks. Electroretinography, histological analysis, and TUNEL assay showed that C3G and its metabolites attenuated retinal cell apoptosis. The expression of oxidative stress markers were upregulated after light exposure but attenuated by C3G and FA, which may be attributed to the elevated secretion and expression of heme oxygenase (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2). C3G, PCA, and FA attenuated the secretion or expression of inflammation-related genes; FA suppressed nuclear factor kappa B (NF-κB) activation. The treatments attenuated the light-induced changes on certain apoptotic proteins and angiogenesis-related cytokines. C3G and FA reduced light-induced retinal oxidative stress by activating the Nrf2/HO-1 antioxidant pathway. FA attenuated the light-induced retinal inflammation by suppressing NF-κB activation. C3G and its metabolites attenuated the photooxidation-induced apoptosis and angiogenesis in the retina. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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

Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA

Mice with cancer-induced bone pain show a marked decline in day/night activity

PubMed Central

Majuta, Lisa A.; Guedon, Jean-Marc G.; Mitchell, Stefanie A.T.; Kuskowski, Michael A.; Mantyh, Patrick W.

2017-01-01

Abstract Introduction: Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. Objectives: To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Methods: Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. Results: As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Conclusion: Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status. PMID:29392229

Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver

PubMed Central

Li, Yu; Xu, Shanqin; Giles, Amber; Nakamura, Kazuto; Lee, Jong Woo; Hou, Xiuyun; Donmez, Gizem; Li, Ji; Luo, Zhijun; Walsh, Kenneth; Guarente, Leonard; Zang, Mengwei

2011-01-01

Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of human type 2 diabetes (T2DM). Although SIRT1 has a therapeutic effect on metabolic deterioration in T2DM, the precise mechanisms by which SIRT1 improves insulin resistance remain unclear. Here, we demonstrate that adenovirus-mediated overexpression of SIRT1 in the liver of diet-induced insulin-resistant low-density lipoprotein receptor-deficient mice and of genetically obese ob/ob mice attenuates hepatic steatosis and ameliorates systemic insulin resistance. These beneficial effects were associated with decreased mammalian target of rapamycin complex 1 (mTORC1) activity, inhibited the unfolded protein response (UPR), and enhanced insulin receptor signaling in the liver, leading to decreased hepatic gluconeogenesis and improved glucose tolerance. The tunicamycin-induced splicing of X-box binding protein-1 and expression of GRP78 and CHOP were reduced by resveratrol in cultured cells in a SIRT1-dependent manner. Conversely, SIRT1-deficient mouse embryonic fibroblasts challenged with tunicamycin exhibited markedly increased mTORC1 activity and impaired ER homeostasi and insulin signaling. These effects were abolished by mTORC1 inhibition by rapamycin in human HepG2 cells. These studies indicate that SIRT1 serves as a negative regulator of UPR signaling in T2DM and that SIRT1 attenuates hepatic steatosis, ameliorates insulin resistance, and restores glucose homeostasis, largely through the inhibition of mTORC1 and ER stress.—Li, Y., Xu, S., Giles, A., Nakamura, K., Lee, J. W., Hou, X., Donmez, G., Li, J., Luo, Z., Walsh, K., Guarente, L., Zang, M. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. PMID:21321189

Novel Intriguing Strategies Attenuating to Sarcopenia

PubMed Central

Sakuma, Kunihiro; Yamaguchi, Akihiko

2012-01-01

Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant. PMID:22500226

Cyclophilin B attenuates the expression of TNF-α in lipopolysaccharide-stimulated macrophages through the induction of B cell lymphoma-3.

PubMed

Marcant, Adeline; Denys, Agnès; Melchior, Aurélie; Martinez, Pierre; Deligny, Audrey; Carpentier, Mathieu; Allain, Fabrice

2012-08-15

Extracellular cyclophilin A (CyPA) and CyPB have been well described as chemotactic factors for various leukocyte subsets, suggesting their contribution to inflammatory responses. Unlike CyPA, CyPB accumulates in extracellular matrixes, from which it is released by inflammatory proteases. Hence, we hypothesized that it could participate in tissue inflammation by regulating the activity of macrophages. In the current study, we confirmed that CyPB initiated in vitro migration of macrophages, but it did not induce production of proinflammatory cytokines. In contrast, pretreatment of macrophages with CyPB attenuated the expression of inflammatory mediators induced by LPS stimulation. The expression of TNF-α mRNA was strongly reduced after exposure to CyPB, but it was not accompanied by significant modification in LPS-induced activation of MAPK and NF-κB pathways. LPS activation of a reporter gene under the control of TNF-α gene promoter was also markedly decreased in cells treated with CyPB, suggesting a transcriptional mechanism of inhibition. Consistent with this hypothesis, we found that CyPB induced the expression of B cell lymphoma-3 (Bcl-3), which was accompanied by a decrease in the binding of NF-κB p65 to the TNF-α promoter. As expected, interfering with the expression of Bcl-3 restored cell responsiveness to LPS, thus confirming that CyPB acted by inhibiting initiation of TNF-α gene transcription. Finally, we found that CyPA was not efficient in attenuating the production of TNF-α from LPS-stimulated macrophages, which seemed to be due to a modest induction of Bcl-3 expression. Collectively, these findings suggest an unexpected role for CyPB in attenuation of the responses of proinflammatory macrophages.

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

PubMed

Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

2012-12-11

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

PubMed

Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

2007-10-01

Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

PubMed Central

Kilpeläinen, Tuomas O.; Qi, Lu; Brage, Soren; Sharp, Stephen J.; Sonestedt, Emily; Demerath, Ellen; Ahmad, Tariq; Mora, Samia; Kaakinen, Marika; Sandholt, Camilla Helene; Holzapfel, Christina; Autenrieth, Christine S.; Hyppönen, Elina; Cauchi, Stéphane; He, Meian; Kutalik, Zoltan; Kumari, Meena; Stančáková, Alena; Meidtner, Karina; Balkau, Beverley; Tan, Jonathan T.; Mangino, Massimo; Timpson, Nicholas J.; Song, Yiqing; Zillikens, M. Carola; Jablonski, Kathleen A.; Garcia, Melissa E.; Johansson, Stefan; Bragg-Gresham, Jennifer L.; Wu, Ying; van Vliet-Ostaptchouk, Jana V.; Onland-Moret, N. Charlotte; Zimmermann, Esther; Rivera, Natalia V.; Tanaka, Toshiko; Stringham, Heather M.; Silbernagel, Günther; Kanoni, Stavroula; Feitosa, Mary F.; Snitker, Soren; Ruiz, Jonatan R.; Metter, Jeffery; Larrad, Maria Teresa Martinez; Atalay, Mustafa; Hakanen, Maarit; Amin, Najaf; Cavalcanti-Proença, Christine; Grøntved, Anders; Hallmans, Göran; Jansson, John-Olov; Kuusisto, Johanna; Kähönen, Mika; Lutsey, Pamela L.; Nolan, John J.; Palla, Luigi; Pedersen, Oluf; Pérusse, Louis; Renström, Frida; Scott, Robert A.; Shungin, Dmitry; Sovio, Ulla; Tammelin, Tuija H.; Rönnemaa, Tapani; Lakka, Timo A.; Uusitupa, Matti; Rios, Manuel Serrano; Ferrucci, Luigi; Bouchard, Claude; Meirhaeghe, Aline; Fu, Mao; Walker, Mark; Borecki, Ingrid B.; Dedoussis, George V.; Fritsche, Andreas; Ohlsson, Claes; Boehnke, Michael; Bandinelli, Stefania; van Duijn, Cornelia M.; Ebrahim, Shah; Lawlor, Debbie A.; Gudnason, Vilmundur; Harris, Tamara B.; Sørensen, Thorkild I. A.; Mohlke, Karen L.; Hofman, Albert; Uitterlinden, André G.; Tuomilehto, Jaakko; Lehtimäki, Terho; Raitakari, Olli; Isomaa, Bo; Njølstad, Pål R.; Florez, Jose C.; Liu, Simin; Ness, Andy; Spector, Timothy D.; Tai, E. Shyong; Froguel, Philippe; Boeing, Heiner; Laakso, Markku; Marmot, Michael; Bergmann, Sven; Power, Chris; Khaw, Kay-Tee; Chasman, Daniel; Ridker, Paul; Hansen, Torben; Monda, Keri L.; Illig, Thomas; Järvelin, Marjo-Riitta; Wareham, Nicholas J.; Hu, Frank B.; Groop, Leif C.; Orho-Melander, Marju; Ekelund, Ulf; Franks, Paul W.; Loos, Ruth J. F.

2011-01-01

Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings All studies identified to have data on the FTO rs9939609 variant (or any proxy [r 2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p interaction  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents. Conclusions The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors' Summary PMID:22069379

Contaminant Attenuation Processes at Mining Sites

EPA Science Inventory

Monitored natural attenuation is sometimes used in combination with active treatment technologies to achieve site-specific remediation objectives. The global imprint of acid drainage problems at mining sites, however, is a clear reminder that in most cases natural processes are ...

Mark Tracking: Position/orientation measurements using 4-circle mark and its tracking experiments

NASA Technical Reports Server (NTRS)

Kanda, Shinji; Okabayashi, Keijyu; Maruyama, Tsugito; Uchiyama, Takashi

1994-01-01

Future space robots require position and orientation tracking with visual feedback control to track and capture floating objects and satellites. We developed a four-circle mark that is useful for this purpose. With this mark, four geometric center positions as feature points can be extracted from the mark by simple image processing. We also developed a position and orientation measurement method that uses the four feature points in our mark. The mark gave good enough image measurement accuracy to let space robots approach and contact objects. A visual feedback control system using this mark enabled a robot arm to track a target object accurately. The control system was able to tolerate a time delay of 2 seconds.

Marking Time

ERIC Educational Resources Information Center

Foster, Colin

2011-01-01

Teachers say that they would gladly teach a day in the classroom if at the end of the day they could leave and have no marking. There is a common staffroom perception that mathematics teachers have it easy when it comes to marking. In arts subjects, setting an essay can be a fairly straightforward matter--a one-line question may suffice--but…

Bioturbation delays attenuation of DDT by clean sediment cap but promotes sequestration by thin-layered activated carbon.

PubMed

Lin, Diana; Cho, Yeo-Myoung; Werner, David; Luthy, Richard G

2014-01-21

The effects of bioturbation on the performance of attenuation by sediment deposition and activated carbon to reduce risks from DDT-contaminated sediment were assessed for DDT sediment-water flux, biouptake, and passive sampler (PE) uptake in microcosm experiments with a freshwater worm, Lumbriculus variegatus. A thin-layer of clean sediment (0.5 cm) did not reduce the DDT flux when bioturbation was present, while a thin (0.3 cm) AC cap was still capable of reducing the DDT flux by 94%. Bioturbation promoted AC sequestration by reducing the 28-day DDT biouptake (66%) and DDT uptake into PE (>99%) compared to controls. Bioturbation further promoted AC-sediment contact by mixing AC particles into underlying sediment layers, reducing PE uptake (55%) in sediment compared to the AC cap without bioturbation. To account for the observed effects from bioturbation, a mass transfer model together with a biodynamic model were developed to simulate DDT flux and biouptake, respectively, and models confirmed experimental results. Both experimental measurements and modeling predictions imply that thin-layer activated carbon placement on sediment is effective in reducing the risks from contaminated sediments in the presence of bioturbation, while natural attenuation process by clean sediment deposition may be delayed by bioturbation.

Improving Marking Quality through a Taxonomy of Mark Schemes

ERIC Educational Resources Information Center

Ahmed, Ayesha; Pollitt, Alastair

2011-01-01

At the heart of most assessments lies a set of questions, and those who write them must achieve "two" things. Not only must they ensure that each question elicits the kind of performance that shows how "good" pupils are at the subject, but they must also ensure that each mark scheme gives more marks to those who are…

Strong Lg-wave attenuation in the Middle East continental collision orogenic belt

NASA Astrophysics Data System (ADS)

Zhao, Lian-Feng; Xie, Xiao-Bi

2016-04-01

Using Lg-wave Q tomography, we construct a broadband crustal attenuation model for the Middle East. The QLg images reveal a relationship between attenuation and geological structures. Strong attenuation is found in the continental collision orogenic belt that extends from the Turkish and Iranian plateau to the Pamir plateau. We investigate the frequency dependence of QLg in different geologic formations. The results illustrate that QLg values generally increase with increasing frequency but exhibit complex relationships both with frequency and between regions. An average QLg value between 0.2 and 2.0 Hz, QLg (0.2-2.0 Hz), may be a critical index for crustal attenuation and is used to infer the regional geology. Low-QLg anomalies are present in the eastern Turkish plateau and correlate well with low Pn-velocities and Cenozoic volcanic activity, thus indicating possible partial melting within the crust in this region. Very strong attenuation is also observed in central Iran, the Afghanistan block, and the southern Caspian Sea. This in line with the previously observed high crustal temperature, high-conductivity layers, and thick marine sediments in these areas, suggests the high Lg attenuation is caused by abnormally high tectonic and thermal activities.

Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.

PubMed

Lindsay, Angus; Othman, Mohd Izani; Prebble, Hannah; Davies, Sian; Gieseg, Steven P

2016-07-01

What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P < 0.001) reduced total neopterin production from the mixed cell culture, whereas cold water immersion significantly (P < 0.05) attenuated urinary neopterin and total neopterin during the training camp without having any effect on physical performance parameters. Soreness and fatigue showed little variation between the groups, whereas training session performance was significantly (P < 0.05) elevated in the cold water immersion group. The data suggest that acute and repetitive cryotherapy

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein

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

Li, Zhijuan, E-mail: zjlee038@163.com; Cheng, Jianxin; Wang, Liping

2015-10-30

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuatedmore » the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. - Highlights: • Edaravone reduces oxLDL-induced monocyte adhesion to HUVECs. • Edaravone attenuates oxLDL-induced expression of MCP-1, VCAM-1, and ICAM-1. • Edaravone reduces NF-κB transcriptional activity and p65 nuclear translocation.« less

Elemental marking of arthropod pests in agricultural systems: single and multigenerational marking

Treesearch

Jane Leslie Hayes

1991-01-01

Use of elemental markers to study movement of arthropod pests of field crops is reviewed. Trace elements, rubidium (Rb) and cesium (Cs), have provided a nondisruptive method of marking natural adult populations via developmental stage consumption of treated host plants. Multigenerational marking occurs with the transfer of elemental markers from marked adults to...

Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models.

PubMed

Shin, Woo-Young; Shim, Do-Wan; Kim, Myong-Ki; Sun, Xiao; Koppula, Sushruta; Yu, Sang-Hyeun; Kim, Han-Bi; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

2017-06-09

Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1β secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders. Copyright © 2017. Published by Elsevier B.V.

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.10 Marking. No person may mark a product or article...

Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

PubMed Central

Hsieh, Yow-Wen; Huang, Ching-Ya; Yang, Shih-Ying; Peng, Yu-Hsuan; Yu, Chung-Ping; Chao, Pei-Dawn Lee; Hou, Yu-Chi

2014-01-01

Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window. EVL is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effect of coadministration of curcumin on the pharmacokinetics of EVL in rats and the underlying mechanisms. EVL (0.5 mg/kg) was orally administered without and with 50 and 100 mg/kg of curcumin, respectively, in rats. Blood samples were collected at specific time points and EVL concentrations in blood were determined by QMS® immunoassay. The underlying mechanisms were evaluated using cell model and recombinant CYP 3A4 isozyme. The results indicated that 50 and 100 mg/kg of curcumin significantly decreased the AUC0-540 of EVL by 70.6% and 71.5%, respectively, and both dosages reduced the Cmax of EVL by 76.7%. Mechanism studies revealed that CYP3A4 was markedly activated by curcumin metabolites, which apparently overrode the inhibition effects of curcumin on P-gp. In conclusion, oral intake of curcumin significantly decreased the bioavailability of EVL, a probe substrate of P-gp/CYP 3A4, mainly through marked activation on CYP 3A4. PMID:25300360

UID.. .Now That's Gonna Leave A Mark

NASA Technical Reports Server (NTRS)

Schramm, Fred

2006-01-01

Since 1975 bar codes on products at the retail counter have been accepted as the standard for entering product identity for price determination. Since the beginning of the 21st century, the Data Matrix symbol has become accepted as the bar code format that is marked directly on a part, assembly or product that is durable enough to identify that item for its lifetime. NASA began the studies for direct part marking Data Matrix symbols on parts during the Return to Flight activities after the Challenger Accident. Over the 20 year period that has elapsed since Challenger, a mountain of studies, analyses and focused problem solutions developed by and for NASA have brought about world changing results. NASA Technical Standard 6002 and NASA Handbook 6003 for Direct Part Marking Data Matrix Symbols on Aerospace Parts have formed the basis for most other standards on part marking internationally. NASA and its commercial partners have developed numerous products and methods that addressed the difficulties of collecting part identification in aerospace operations. These products enabled the marking of Data Matrix symbols in virtually every situation and the reading of symbols at great distances, severe angles, under paint and in the dark without a light. Even unmarkable delicate parts now have a process to apply a chemical mixture, recently trademarked as Nanocodes, that can be converted to Data Matrix information through software. The accompanying intellectual property is protected by ten patents, several of which are licensed. Direct marking Data Matrix on NASA parts dramatically decreases data entry errors and the number of parts that go through their life cycle marked, two major threats to sound configuration management and flight safety. NASA is said to only have people and stuff with information connecting them. Data Matrix is one of the most significant improvements since Challenger to the safety and reliability of that connection.

Activation and overexpression of Sirt1 attenuates lung fibrosis via P300.

PubMed

Zeng, Zhilin; Cheng, Sheng; Chen, Huilong; Li, Qinghai; Hu, Yinan; Wang, Qi; Zhu, Xianying; Wang, Jun

2017-05-13

Persistent fibroblast activation is a predominant feature of idiopathic pulmonary fibrosis (IPF), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. Silent information regulator type-1 (Sirt1) is a member of class Ⅲ histone deacetylase with important regulatory roles in a variety of pathophysiologic processes, but its role in fibrotic lung diseases is not clearly elucidated. Sirt1 expression in lung tissues of IPF patients and in a mouse model of bleomycin (BLM)-induced lung fibrosis were evaluated by immunofluorescence. The function of Sirt1 in BLM-induced lung fibrosis in the mouse model or transforming growth factor β1 (TGF-β1)-mediated lung fibroblast cellular model was investigated by Sirt1 activation, overexpression and knockdown of Sirt1. Finally, the involvement of p300 signaling pathways was assessed. In this study, we found up-regulation of Sirt1 in BLM-induced lung fibrosis, as well as in the lungs of IPF patients, including in the aggregated pulmonary fibroblasts of fibrotic foci. Activation or overexpression of Sirt1 attenuated TGF-β1-mediated lung fibroblast differentiation and activation and diminished the severity of experimental lung fibrosis in mice. Whereas knockdown of Sirt1 promoted the pro-fibrogenic activity of TGF-β1 in lung fibroblasts. A potential mechanism for the role of Sirt1 in lung fibrosis was through regulating the expression of p300. Thus, we characterized Sirt1 as an important regulator of lung fibrosis and provides a proof of principle for activation or overexpression of Sirt1 as a potential novel therapeutic strategy for IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Control algorithms for dynamic attenuators

PubMed Central

Hsieh, Scott S.; Pelc, Norbert J.

2014-01-01

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators.

PubMed

Hsieh, Scott S; Pelc, Norbert J

2014-06-01

The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

Cyclopropanyldehydrocostunolide LJ attenuates high glucose-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways.

PubMed

Chen, Xiao-Wen; Liu, Wen-Ting; Wang, Yu-Xian; Chen, Wen-Jing; Li, Hong-Yu; Chen, Yi-Hua; Du, Xiao-Yan; Peng, Fen-Fen; Zhou, Wei-Dong; Xu, Zhao-Zhong; Long, Hai-Bo

2016-07-01

The aim of this research was to investigate the effects of cyclopropanyldehydrocostunolide (also named LJ), a derivative of sesquiterpene lactones (SLs), on high glucose (HG)-induced podocyte injury and the associated molecular mechanisms. Differentiated mouse podocytes were incubated in different treatments. The migration and albumin filtration of podocytes were examined by Transwell filters. The protein and mRNA levels of MCP-1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (q-PCR). Protein expression and phosphorylation were detected by western blot, and the nuclear translocation of NF-κB was performed with a confocal microscope. The gene expression of the receptor activator for NF-κB (RANK) was silenced by small interfering RNA (siRNA). Our results showed that HG enhanced migration, albumin filtration and MCP-1 expression in podocytes. At the molecular level, HG promoted the phosphorylation of NF-κB/p65, IKKβ, IκBα, mitogen-activated protein kinase (MAPK) and the nuclear translocation of p65. LJ reversed the effects of HG in a dose-dependent manner. Furthermore, our data provided the first demonstration that the receptor activator for NF-κB ligand (RANKL) and its cognate receptor RANK were overexpressed in HG-induced podocytes and were downregulated by LJ. RANK siRNA also attenuated HG-induced podocyte injury and markedly inhibited the activation of NF-κB and MAPK signaling pathways. LJ attenuates HG-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots

PubMed Central

Wu, Zhen; Fallahi, Mohammad; Ouizem, Souad; Liu, Qin; Li, Weimin; Costi, Roberta; Roush, William R.; Bois, Philippe R. J.

2016-01-01

ABSTRACT Meiotic recombination initiates following the formation of DNA double-strand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined “hot spots.” In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these open chromatin-associated histone marks is dynamic and is manifest at spermatogonia and/or pre-leptotene-stage cells, which facilitates PRDM9 binding and access for Spo11 to direct the formation of DSBs, which are initiated at the leptotene stage. Importantly, manipulating histone acetylase and deacetylase activities established that histone acetylation marks are necessary for both hot spot activity and crossover resolution. We conclude that there are functional roles for histone acetylation marks at mammalian meiotic recombination hot spots. PMID:27821479

Effects of light attenuation on the sponge holobiont- implications for dredging management

PubMed Central

Pineda, Mari-Carmen; Strehlow, Brian; Duckworth, Alan; Doyle, Jason; Jones, Ross; Webster, Nicole S.

2016-01-01

Dredging and natural sediment resuspension events can cause high levels of turbidity, reducing the amount of light available for photosynthetic benthic biota. To determine how marine sponges respond to light attenuation, five species were experimentally exposed to a range of light treatments. Tolerance thresholds and capacity for recovery varied markedly amongst species. Whilst light attenuation had no effect on the heterotrophic species Stylissa flabelliformis and Ianthella basta, the phototrophic species Cliona orientalis and Carteriospongia foliascens discoloured (bleached) over a 28 day exposure period to very low light (<0.8 mol photons m−2 d−1). In darkness, both species discoloured within a few days, concomitant with reduced fluorescence yields, chlorophyll concentrations and shifts in their associated microbiomes. The phototrophic species Cymbastela coralliophila was less impacted by light reduction. C. orientalis and C. coralliophila exhibited full recovery under normal light conditions, whilst C. foliascens did not recover and showed high levels of mortality. The light treatments used in the study are directly relevant to conditions that can occur in situ during dredging projects, indicating that light attenuation poses a risk to photosynthetic marine sponges. Examining benthic light levels over temporal scales would enable dredging proponents to be aware of conditions that could impact on sponge physiology. PMID:27958345

Effects of light attenuation on the sponge holobiont- implications for dredging management.

PubMed

Pineda, Mari-Carmen; Strehlow, Brian; Duckworth, Alan; Doyle, Jason; Jones, Ross; Webster, Nicole S

2016-12-13

Dredging and natural sediment resuspension events can cause high levels of turbidity, reducing the amount of light available for photosynthetic benthic biota. To determine how marine sponges respond to light attenuation, five species were experimentally exposed to a range of light treatments. Tolerance thresholds and capacity for recovery varied markedly amongst species. Whilst light attenuation had no effect on the heterotrophic species Stylissa flabelliformis and Ianthella basta, the phototrophic species Cliona orientalis and Carteriospongia foliascens discoloured (bleached) over a 28 day exposure period to very low light (<0.8 mol photons m -2 d -1 ). In darkness, both species discoloured within a few days, concomitant with reduced fluorescence yields, chlorophyll concentrations and shifts in their associated microbiomes. The phototrophic species Cymbastela coralliophila was less impacted by light reduction. C. orientalis and C. coralliophila exhibited full recovery under normal light conditions, whilst C. foliascens did not recover and showed high levels of mortality. The light treatments used in the study are directly relevant to conditions that can occur in situ during dredging projects, indicating that light attenuation poses a risk to photosynthetic marine sponges. Examining benthic light levels over temporal scales would enable dredging proponents to be aware of conditions that could impact on sponge physiology.

Attenuation of reflected waves in man during retrograde propagation from femoral artery to proximal aorta.

PubMed

Baksi, A John; Davies, Justin E; Hadjiloizou, Nearchos; Baruah, Resham; Unsworth, Beth; Foale, Rodney A; Korolkova, Olga; Siggers, Jennifer H; Francis, Darrel P; Mayet, Jamil; Parker, Kim H; Hughes, Alun D

2016-01-01

Wave reflection may be an important influence on blood pressure, but the extent to which reflections undergo attenuation during retrograde propagation has not been studied. We quantified retrograde transmission of a reflected wave created by occlusion of the left femoral artery in man. 20 subjects (age 31-83 years; 14 male) underwent invasive measurement of pressure and flow velocity with a sensor-tipped intra-arterial wire at multiple locations distal to the proximal aorta before, during and following occlusion of the left femoral artery by thigh cuff inflation. A numerical model of the circulation was also used to predict reflected wave transmission. Wave reflection was measured as the ratio of backward to forward wave energy (WRI) and the ratio of peak backward to forward pressure (Pb/Pf). Cuff inflation caused a marked reflection which was largest at 5-10 cm from the cuff (change (Δ) in WRI=0.50 (95% CI 0.38, 0.62); p<0.001, ΔPb/Pf=0.23 (0.18-0.29); p<0.001). The magnitude of the cuff-induced reflection decreased progressively at more proximal locations and was barely discernible at sites>40 cm from the cuff including in the proximal aorta. Numerical modelling gave similar predictions to those observed experimentally. Reflections due to femoral artery occlusion are markedly attenuated by the time they reach the proximal aorta. This is due to impedance mismatches of bifurcations traversed in the backward direction. This degree of attenuation is inconsistent with the idea of a large discrete reflected wave arising from the lower limb and propagating back into the aorta. Copyright © 2015. Published by Elsevier Ireland Ltd.

Activating PXR by Imperatorin Attenuates Dextran Sulphate Sodium-Induced Colitis in Mice.

PubMed

Liu, Meijing; Zhang, Guohui; Zheng, Chunge; Song, Meng; Liu, Fangle; Huang, Xiaotao; Bai, Shasha; Huang, Xinan; Lin, Chaozhan; Zhu, Chenchen; Hu, Yingjie; Mi, Suiqing; Liu, Changhui

2018-06-26

The activation of human pregnane X receptor (PXR) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally-occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD. The effects of IMP on PXR-modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis of CYP3A4 mRNA and protein expression levels, and measurement of CYP3A4 activity using a cell-based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF-κB activity was evaluated by a reporter assay and NF-κB p65 nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines were assessed by ELISA. IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 (SRC-1) to the ligand-binding domain of PXR, and increased the expression and activity of CYP3A4. However, PXR knockdown substantially reduced PXR-mediated CYP3A4 expression. Furthermore, IMP-mediated PXR activation suppressed NF-κB nuclear translocation and downregulated lipopolysaccharide-induced proinflammatory gene expression. Nevertheless, PXR knockdown partially reduced the IMP-mediated inhibition of NF-κB. IMP ameliorated DSS-induced colitis by PXR/NF-κB signalling. IMP serves as a PXR agonist to attenuate DSS-induced colitis by the suppression of the NF-κB-mediated proinflammatory response in a PXR/NF-κB- dependent manner. This article is protected by copyright. All rights reserved.

Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

PubMed Central

Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

2015-01-01

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

Active Recovery After High-Intensity Interval-Training Does Not Attenuate Training Adaptation.

PubMed

Wiewelhove, Thimo; Schneider, Christoph; Schmidt, Alina; Döweling, Alexander; Meyer, Tim; Kellmann, Michael; Pfeiffer, Mark; Ferrauti, Alexander

2018-01-01

Objective: High-intensity interval training (HIIT) can be extremely demanding and can consequently produce high blood lactate levels. Previous studies have shown that lactate is a potent metabolic stimulus, which is important for adaptation. Active recovery (ACT) after intensive exercise, however, enhances blood lactate removal in comparison with passive recovery (PAS) and, consequently, may attenuate endurance performance improvements. Therefore, the aim of this study was to examine the influence of regular ACT on training adaptations during a HIIT mesocycle. Methods: Twenty-six well-trained male intermittent sport athletes (age: 23.5 ± 2.5 years; O 2 max: 55.36 ± 3.69 ml min kg -1 ) participated in a randomized controlled trial consisting of 4 weeks of a running-based HIIT mesocycle with a total of 12 HIIT sessions. After each training session, participants completed 15 min of either moderate jogging (ACT) or PAS. Subjects were matched to the ACT or PAS groups according to age and performance. Before the HIIT program and 1 week after the last training session, the athletes performed a progressive incremental exercise test on a motor-driven treadmill to determine O 2 max, maximum running velocity (vmax), the running velocity at which O 2 max occurs (vO 2 max), and anaerobic lactate threshold (AT). Furthermore, repeated sprint ability (RSA) were determined. Results: In the whole group the HIIT mesocycle induced significant or small to moderate changes in vmax ( p < 0.001, effect size [ES] = 0.65,), vO 2 max ( p < 0.001, ES = 0.62), and AT ( p < 0.001, ES = 0.56) compared with the values before the intervention. O 2 max and RSA remained unchanged throughout the study. In addition, no significant differences in the changes were noted in any of the parameters between ACT and PAS except for AT ( p < 0.05, ES = 0.57). Conclusion: Regular use of individualized ACT did not attenuate training adaptations during a HIIT mesocycle compared to PAS. Interestingly, we found

Active Recovery After High-Intensity Interval-Training Does Not Attenuate Training Adaptation

PubMed Central

Wiewelhove, Thimo; Schneider, Christoph; Schmidt, Alina; Döweling, Alexander; Meyer, Tim; Kellmann, Michael; Pfeiffer, Mark; Ferrauti, Alexander

2018-01-01

Objective: High-intensity interval training (HIIT) can be extremely demanding and can consequently produce high blood lactate levels. Previous studies have shown that lactate is a potent metabolic stimulus, which is important for adaptation. Active recovery (ACT) after intensive exercise, however, enhances blood lactate removal in comparison with passive recovery (PAS) and, consequently, may attenuate endurance performance improvements. Therefore, the aim of this study was to examine the influence of regular ACT on training adaptations during a HIIT mesocycle. Methods: Twenty-six well-trained male intermittent sport athletes (age: 23.5 ± 2.5 years; O2max: 55.36 ± 3.69 ml min kg-1) participated in a randomized controlled trial consisting of 4 weeks of a running-based HIIT mesocycle with a total of 12 HIIT sessions. After each training session, participants completed 15 min of either moderate jogging (ACT) or PAS. Subjects were matched to the ACT or PAS groups according to age and performance. Before the HIIT program and 1 week after the last training session, the athletes performed a progressive incremental exercise test on a motor-driven treadmill to determine O2max, maximum running velocity (vmax), the running velocity at which O2max occurs (vO2max), and anaerobic lactate threshold (AT). Furthermore, repeated sprint ability (RSA) were determined. Results: In the whole group the HIIT mesocycle induced significant or small to moderate changes in vmax (p < 0.001, effect size [ES] = 0.65,), vO2max (p < 0.001, ES = 0.62), and AT (p < 0.001, ES = 0.56) compared with the values before the intervention. O2max and RSA remained unchanged throughout the study. In addition, no significant differences in the changes were noted in any of the parameters between ACT and PAS except for AT (p < 0.05, ES = 0.57). Conclusion: Regular use of individualized ACT did not attenuate training adaptations during a HIIT mesocycle compared to PAS. Interestingly, we found that the ACT group

The alpha (α)-glucosidase inhibitor, acarbose, attenuates the blood pressure and splanchnic blood flow responses to intraduodenal sucrose in older adults.

PubMed

Gentilcore, Diana; Vanis, Lora; Wishart, Judith M; Rayner, Christopher K; Horowitz, Michael; Jones, Karen L

2011-08-01

Postprandial hypotension is an important problem in the elderly and may be triggered by the increase in splanchnic blood flow induced by a meal. Acarbose attenuates the fall in blood pressure (BP) induced by oral sucrose and may be useful in the management of postprandial hypotension. It is not known whether the effect of acarbose on postprandial BP reflects slowing of gastric emptying and/or carbohydrate absorption nor whether acarbose affects splanchnic blood flow. We examined the effects of intraduodenal (ID) acarbose on the BP, heart rate, superior mesenteric artery (SMA) flow, and glycemic and insulin responses to ID sucrose in older participants--this approach excluded any "gastric" effect of acarbose. Eight healthy participants (four male and four female, age 66-77 years) received an ID infusion of sucrose (~6 kcal/min), with or without acarbose (100 mg), over 60 minutes. BP, heart rate, SMA flow, blood glucose, and serum insulin were measured. Acarbose markedly attenuated the falls in systolic (p < .01) and diastolic (p < .05) BP and rises in heart rate (p < .05), SMA flow (p < .05), blood glucose (p < .01), and serum insulin (p < .05). The maximum fall in systolic BP and peak SMA flow was inversely related on the control day (r(2) = -.53, p < .05) but not with acarbose (r(2) = .03, p = .70). We conclude that in healthy older participants receiving ID sucrose, (a) acarbose markedly attenuates the hypotensive response by slowing carbohydrate absorption and attenuating the rise in splanchnic blood flow and (b) the fall in BP is related to the concomitant increase in SMA flow.

Tracer attenuation in groundwater

NASA Astrophysics Data System (ADS)

Cvetkovic, Vladimir

2011-12-01

The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

Mark-recapture and mark-resight methods for estimating abundance with remote cameras: a carnivore case study

USGS Publications Warehouse

Alanso, Robert S.; McClintock, Brett T.; Lyren, Lisa M.; Boydston, Erin E.; Crooks, Kevin R.

2015-01-01

Abundance estimation of carnivore populations is difficult and has prompted the use of non-invasive detection methods, such as remotely-triggered cameras, to collect data. To analyze photo data, studies focusing on carnivores with unique pelage patterns have utilized a mark-recapture framework and studies of carnivores without unique pelage patterns have used a mark-resight framework. We compared mark-resight and mark-recapture estimation methods to estimate bobcat (Lynx rufus) population sizes, which motivated the development of a new "hybrid" mark-resight model as an alternative to traditional methods. We deployed a sampling grid of 30 cameras throughout the urban southern California study area. Additionally, we physically captured and marked a subset of the bobcat population with GPS telemetry collars. Since we could identify individual bobcats with photos of unique pelage patterns and a subset of the population was physically marked, we were able to use traditional mark-recapture and mark-resight methods, as well as the new “hybrid” mark-resight model we developed to estimate bobcat abundance. We recorded 109 bobcat photos during 4,669 camera nights and physically marked 27 bobcats with GPS telemetry collars. Abundance estimates produced by the traditional mark-recapture, traditional mark-resight, and “hybrid” mark-resight methods were similar, however precision differed depending on the models used. Traditional mark-recapture and mark-resight estimates were relatively imprecise with percent confidence interval lengths exceeding 100% of point estimates. Hybrid mark-resight models produced better precision with percent confidence intervals not exceeding 57%. The increased precision of the hybrid mark-resight method stems from utilizing the complete encounter histories of physically marked individuals (including those never detected by a camera trap) and the encounter histories of naturally marked individuals detected at camera traps. This new estimator

Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-Induced Apoptosis and Lung Injury in Mice.

PubMed

Nagamine, Yusuke; Tojo, Kentaro; Yazawa, Takuya; Takaki, Shunsuke; Baba, Yasuko; Goto, Takahisa; Kurahashi, Kiyoyasu

2016-12-01

Alveolar epithelial injury and increased alveolar permeability are hallmarks of acute respiratory distress syndrome. Apoptosis of lung epithelial cells via the Fas/Fas ligand (FasL) pathway plays a critical role in alveolar epithelial injury. Activation of hypoxia-inducible factor (HIF)-1 by inhibition of prolyl hydroxylase domain proteins (PHDs) is a possible therapeutic approach to attenuate apoptosis and organ injury. Here, we investigated whether treatment with dimethyloxalylglycine (DMOG), an inhibitor of PHDs, could attenuate Fas/FasL-dependent apoptosis in lung epithelial cells and lung injury. DMOG increased HIF-1α protein expression in vitro in MLE-12 cells, a murine alveolar epithelial cell line. Treatment of MLE-12 cells with DMOG significantly suppressed cell surface expression of Fas and attenuated FasL-induced caspase-3 activation and apoptotic cell death. Inhibition of the HIF-1 pathway by echinomycin or small interfering RNA transfection abolished these antiapoptotic effects of DMOG. Moreover, intraperitoneal injection of DMOG in mice increased HIF-1α expression and decreased Fas expression in lung tissues. DMOG treatment significantly attenuated caspase-3 activation, apoptotic cell death in lung tissue, and the increase in alveolar permeability in mice instilled intratracheally with FasL. In addition, inflammatory responses and histopathological changes were also significantly attenuated by DMOG treatment. In conclusion, inhibition of PHDs protects lung epithelial cells from Fas/FasL-dependent apoptosis through HIF-1 activation and attenuates lung injury in mice.

Active thermography and post-processing image enhancement for recovering of abraded and paint-covered alphanumeric identification marks

NASA Astrophysics Data System (ADS)

Montanini, R.; Quattrocchi, A.; Piccolo, S. A.

2016-09-01

Alphanumeric marking is a common technique employed in industrial applications for identification of products. However, the realised mark can undergo deterioration, either by extensive use or voluntary deletion (e.g. removal of identification numbers of weapons or vehicles). For recovery of the lost data many destructive or non-destructive techniques have been endeavoured so far, which however present several restrictions. In this paper, active infrared thermography has been exploited for the first time in order to assess its effectiveness in restoring paint covered and abraded labels made by means of different manufacturing processes (laser, dot peen, impact, cold press and scribe). Optical excitation of the target surface has been achieved using pulse (PT), lock-in (LT) and step heating (SHT) thermography. Raw infrared images were analysed with a dedicated image processing software originally developed in Matlab™, exploiting several methods, which include thermographic signal reconstruction (TSR), guided filtering (GF), block guided filtering (BGF) and logarithmic transformation (LN). Proper image processing of the raw infrared images resulted in superior contrast and enhanced readability. In particular, for deeply abraded marks, good outcomes have been obtained by application of logarithmic transformation to raw PT images and block guided filtering to raw phase LT images. With PT and LT it was relatively easy to recover labels covered by paint, with the latter one providing better thermal contrast for all the examined targets. Step heating thermography never led to adequate label identification instead.

Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin.

PubMed

Ando, Masaki; Oku, Naoto; Takeda, Atsushi

2010-11-01

The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CA3 synapse. Zinc is released with glutamate from mossy fiber terminals. However, the role of the zinc in mossy fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of mossy fiber LTP was examined in that induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2), whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced mossy fiber LTP was attenuated by perfusion with 100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre-perfusion did not attenuate mossy fiber LTP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 microM ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 microM ZnCl(2). These results suggest that zinc taken up into mossy fibers attenuates forskolin-induced mossy fiber LTP via inhibition of AC activity. The significance of endogenous zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber LTP. Copyright 2010 Elsevier Ltd. All rights reserved.

Biomass conversion inhibitors furfural and 5-hydroxymethylfurfural induce formation of messenger RNP granules and attenuate translation activity in Saccharomyces cerevisiae.

PubMed

Iwaki, Aya; Kawai, Takao; Yamamoto, Yosuke; Izawa, Shingo

2013-03-01

Various forms of stress can cause an attenuation of bulk translation activity and the accumulation of nontranslating mRNAs into cytoplasmic messenger RNP (mRNP) granules termed processing bodies (P-bodies) and stress granules (SGs) in eukaryotic cells. Furfural and 5-hydroxymethylfurfural (HMF), derived from lignocellulosic biomass, inhibit yeast growth and fermentation as stressors. Since there is no report regarding their effects on the formation of cytoplasmic mRNP granules, here we investigated whether furfural and HMF cause the assembly of yeast P-bodies and SGs accompanied by translational repression. We found that furfural and HMF cause the attenuation of bulk translation activity and the assembly of cytoplasmic mRNP granules in Saccharomyces cerevisiae. Notably, a combination of furfural and HMF induced the remarkable repression of translation initiation and SG formation. These findings provide new information about the physiological effects of furfural and HMF on yeast cells, and also suggest the potential usefulness of cytoplasmic mRNP granules as a warning sign or index of the deterioration of cellular physiological status in the fermentation of lignocellulosic hydrolysates.

Biomass Conversion Inhibitors Furfural and 5-Hydroxymethylfurfural Induce Formation of Messenger RNP Granules and Attenuate Translation Activity in Saccharomyces cerevisiae

PubMed Central

Iwaki, Aya; Kawai, Takao; Yamamoto, Yosuke

2013-01-01

Various forms of stress can cause an attenuation of bulk translation activity and the accumulation of nontranslating mRNAs into cytoplasmic messenger RNP (mRNP) granules termed processing bodies (P-bodies) and stress granules (SGs) in eukaryotic cells. Furfural and 5-hydroxymethylfurfural (HMF), derived from lignocellulosic biomass, inhibit yeast growth and fermentation as stressors. Since there is no report regarding their effects on the formation of cytoplasmic mRNP granules, here we investigated whether furfural and HMF cause the assembly of yeast P-bodies and SGs accompanied by translational repression. We found that furfural and HMF cause the attenuation of bulk translation activity and the assembly of cytoplasmic mRNP granules in Saccharomyces cerevisiae. Notably, a combination of furfural and HMF induced the remarkable repression of translation initiation and SG formation. These findings provide new information about the physiological effects of furfural and HMF on yeast cells, and also suggest the potential usefulness of cytoplasmic mRNP granules as a warning sign or index of the deterioration of cellular physiological status in the fermentation of lignocellulosic hydrolysates. PMID:23275506

Lujan Mark-4

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

Mocko, Michael Jeffrey; Zavorka, Lukas; Koehler, Paul E.

2017-11-13

This is a review of Mark-IV target neutronics design. It involved the major redesign of the upper tier, offering harder neutron spectra for upper-tier FPs; a redesign of the high-resolution (HR) moderator; and a preservation of the rest of Mark-III features.

Minimal Marking: A Success Story

ERIC Educational Resources Information Center

McNeilly, Anne

2014-01-01

The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

14 CFR 45.10 - Marking.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Marking. 45.10 Section 45.10 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Identification of Aircraft and Related Products § 45.10 Marking. No person may mark a...

The utility of harvest recoveries of marked individuals to assess polar bear (Ursus maritimus) survival

USGS Publications Warehouse

Peacock, Elizabeth; Laake, Jeff; Laidre, Kristin L.; Born, Erik W.; Atkinson, Stephen N.

2012-01-01

Management of polar bear (Ursus maritimus) populations requires the periodic assessment of life history metrics such as survival rate. This information is frequently obtained during short-term capture and marking efforts (e.g., over the course of three years) that result in hundreds of marked bears remaining in the population after active marking is finished. Using 10 additional years of harvest recovery subsequent to a period of active marking, we provide updated estimates of annual survival for polar bears in the Baffin Bay population of Greenland and Canada. Our analysis suggests a decline in survival of polar bears since the period of active marking that ended in 1997; some of the decline in survival can likely be attributed to a decline in springtime ice concentration over the continental shelf of Baffin Island. The variance around the survival estimates is comparatively high because of the declining number of marks available; therefore, results must be interpreted with caution. The variance of the estimates of survival increased most substantially in the sixth year post-marking. When survival estimates calculated with recovery-only and recapture-recovery data sets from the period of active marking were compared, survival rates were indistinguishable. However, for the period when fewer marks were available, survival estimates were lower using the recovery-only data set, which indicates that part of the decline we detected for 2003 – 09 may be due to using only harvest recovery data. Nevertheless, the decline in the estimates of survival is consistent with population projections derived from harvest numbers and earlier vital rates, as well as with an observed decline in the extent of sea ice habitat.

Attenuation of near-IR light through dentin at wavelengths from 1300–1650-nm

PubMed Central

Chan, Andrew C.; Darling, Cynthia L.; Chan, Kenneth H.; Fried, Daniel

2014-01-01

Light scattering in dental enamel decreases markedly from the UV to the near-IR and recent studies employing near-IR transillumination and reflectance imaging including optical coherence tomography indicate that this wavelength region is ideally suited for imaging dental caries due to the high transparency of enamel. The opacity of dentin is an important factor in optimizing the contrast of demineralization in reflectance measurements. It also influences the contrast of occlusal lesions in transillumination. Light scattering in dentin is an order of magnitude larger than in enamel, it is highly anisotropic and has a different spectral light scattering dependence than enamel. The objective of this study was to measure the optical attenuation of near-IR light through dentin at near-IR wavelengths from 1300–1650-nm. In this study the collimated transmission of near-IR light through polished thin sections of dentin of 0.05 to 0.6 mm thickness was measured. Beer-Lambert plots show that the attenuation coefficients range in magnitude from 20 to 40 cm−1. Attenuation increased significantly with increasing wavelength and the increases were not entirely consistent with increased water absorption. PMID:24839373

Propofol inhibits gap junctions by attenuating sevoflurane-induced cytotoxicity against rat liver cells in vitro.

PubMed

Huang, Fei; Li, Shangrong; Gan, Xiaoliang; Wang, Ren; Chen, Zhonggang

2014-04-01

Liver abnormalities are seen in a small proportion of patients following anaesthesia with sevoflurane. To investigate whether the cytotoxicity of sevoflurane against rat liver cells was mediated by gap junction intercellular communications, and the effect of propofol on sevoflurane-induced cytotoxicity. Experimental study. The study was carried out in the central laboratory of The Third Affiliated Hospital, Sun Yat-sen University. BRL-3A rat liver cells. Immortal rat liver cells BRL-3A were grown at low and high density. Colony-forming assays were performed to determine clonogenic growth of these cells. To investigate the effect of oleamide and propofol on gap junction function, we measured fluorescence transmission between cells using parachute dye-coupling assays. Immunoblotting assays were performed to determine connexin32 and connexin43 expression. Our colony formation assays revealed that, in low-density culture, sevoflurane caused no apparent inhibition of clonogenic growth of BRL-3A cells. In high-density culture, 2.2 to 4.4% sevoflurane markedly inhibited clonogenic growth of BRL-3A cells with 67.6 (0.34)% and 61.2 (0.17)% of the cells being viable, respectively (P = 0.003 vs. low-density culture), suggesting cell density dependency of sevoflurane-induced cytotoxicity. Our colony formation assays revealed that propofol markedly attenuated the suppression by sevoflurane of the clonogenic growth of BRL-3A cells (viability: propofol and sevoflurane, 91.5 (0.014)% vs. sevoflurane, 56.6 (0.019)%; P <0.01). Blocking gap junctions with 10 μmol l oleamide significantly attenuated 4.4% sevoflurane-induced suppression with a viability of 83.6 ± 0.138% (oleamide and sevoflurane vs. sevoflurane, P < 0.01). Immunoblotting assays further showed that propofol (3.2 μg ml) markedly reduced CX32 levels and significantly inhibited gap junctional intercellular communications as revealed by parachute dye-coupling assays. Values are mean (SD). This study

Variable laser attenuator

DOEpatents

Foltyn, Stephen R.

1988-01-01

The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

Marking cell lineages in living tissues.

PubMed

Kurup, Smita; Runions, John; Köhler, Uwe; Laplaze, Laurent; Hodge, Sarah; Haseloff, Jim

2005-05-01

We have generated a novel genetic system to visualize cell lineages in living tissues at high resolution. Heat shock was used to trigger the excision of a specific transposon and activation of a fluorescent marker gene. A histone-YFP marker was used to allow identification of cell lineages and easy counting of cells. Constitutive expression of a green fluorescent membrane protein was used to provide a precise outline of all surrounding cells. Marked lineages can be induced from specific cells within the organism by targeted laser irradiation, and the fate of the marked cells can be followed non-invasively. We have used the system to map cell lineages originating from the initials of primary and lateral roots in Arabidopsis. The lineage marking technique enabled us to measure the differential contribution of primary root pericycle cell files to developing lateral root primordia. The majority of cells in an emerging lateral root primordium derive from the central file of pericycle founder cells while off-centre founder cells contribute only a minor proliferation of tissue near the base of the root. The system shows great promise for the detailed study of cell division during morphogenesis.

D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury

PubMed Central

Miyahara, Takuya; Runge, Sara; Chatterjee, Anuran; Chen, Mian; Mottola, Giorgio; Fitzgerald, Jonathan M.; Serhan, Charles N.; Conte, Michael S.

2013-01-01

Recent evidence suggests that specialized lipid mediators derived from polyunsaturated fatty acids control resolution of inflammation, but little is known about resolution pathways in vascular injury. We sought to determine the actions of D-series resolvin (RvD) on vascular smooth muscle cell (VSMC) phenotype and vascular injury. Human VSMCs were treated with RvD1 and RvD2, and phenotype was assessed by proliferation, migration, monocyte adhesion, superoxide production, and gene expression assays. A rabbit model of arterial angioplasty with local delivery of RvD2 (10 nM vs. vehicle control) was employed to examine effects on vascular injury in vivo. Local generation of proresolving lipid mediators (LC-MS/MS) and expression of RvD receptors in the vessel wall were assessed. RvD1 and RvD2 produced dose-dependent inhibition of VSMC proliferation, migration, monocyte adhesion, superoxide production, and proinflammatory gene expression (IC50≈0.1–1 nM). In balloon-injured rabbit arteries, cell proliferation (51%) and leukocyte recruitment (41%) were reduced at 3 d, and neointimal hyperplasia was attenuated (29%) at 28 d by RvD2. We demonstrate endogenous biosynthesis of proresolving lipid mediators and expression of receptors for RvD1 in the artery wall. RvDs broadly reduce VSMC responses and modulate vascular injury, suggesting that local activation of resolution mechanisms expedites vascular homeostasis.—Miyahara, T., Runge, S., Chatterjee, A., Chen, M., Mottola, G., Fitzgerald, J. M., Serhan, C. N., Conte, M. S. D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. PMID:23407709

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development.

PubMed

Sakai, Hiroyasu; Tabata, Shoko; Kimura, Minami; Yabe, Saori; Isa, Yosuke; Kai, Yuki; Sato, Fumiaki; Yumoto, Tetsuro; Miyano, Kanako; Narita, Minoru; Uezono, Yasuhito

2017-01-01

5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

Laser marking as environment technology

NASA Astrophysics Data System (ADS)

Sobotova, Lydia; Badida, Miroslav

2017-11-01

The contribution deals with the laser marking as one of the progressive and environment friendly technologies with utilisation in many branches of industry. Engraving and other types of laser marking of different types of materials are very actual technologies these days. Laser marking decreases the waste creation in comparison with the other classical marking technologies, which use paintings or created chips. In this experimental investigation the laser marking surface texturing of material AL99,7 according to STN 42 4003:1993-08 (STN EN 573) has been conducted. The laser marking machine TruMark 6020 and software TruTops Mark were used. Laser surface texturing after laser marking has been realised under different combinations of process parameters: pulse frequency, pulse energy and laser beam scanning speed. The morphological characterization of engraving or annealing surfaces has been performed using scanning electron microscopy (SEM) technique. The evaluation of roughness of engraved surfaces has been realized according to STN EN ISO 4287 by using Surftest SJ 301. The aim of the contribution was to show how different laser parameters affect the surface texture and colour change of metallic materials while creating minimal waste.

A description of shock attenuation for children running.

PubMed

Mercer, John A; Dufek, Janet S; Mangus, Brent C; Rubley, Mack D; Bhanot, Kunal; Aldridge, Jennifer M

2010-01-01

A growing number of children are participating in organized sport activities, resulting in a concomitant increase in lower extremity injuries. Little is known about the impact generated when children are running or how this impact is attenuated in child runners. To describe shock attenuation characteristics for children running at different speeds on a treadmill and at a single speed over ground. Prospective cohort study. Biomechanics laboratory. Eleven boys (age = 10.5 +/- 0.9 years, height = 143.7 +/- 8.3 cm, mass = 39.4 +/- 10.9 kg) and 7 girls (age = 9.9 +/- 1.1 years, height = 136.2 +/- 7.7 cm, mass = 35.1 +/- 9.6 kg) participated. Participants completed 4 running conditions, including 3 treadmill (TM) running speeds (preferred, fast [0.5 m/s more than preferred], and slow [0.5 m/s less than preferred]) and 1 overground (OG) running speed. We measured leg peak impact acceleration (LgPk), head peak impact acceleration (HdPk), and shock attenuation (ratio of LgPk to HdPk). Shock attenuation (F(2,16) = 4.80, P = .01) was influenced by the interaction of speed and sex. Shock attenuation increased across speeds (slow, preferred, fast) for boys (P < .05) but not for girls (P > .05). Both LgPk (F(1,16) = 5.04, P = .04) and HdPk (F(1,16) = 6.04, P = .03) were different across speeds, and both were greater for girls than for boys. None of the dependent variables were influenced by the interaction of setting (TM, OG) and sex (P >or= .05). Shock attenuation (F(1,16) = 33.51, P < .001) and LgPk (F(1,16) = 31.54, P < .001) were different between TM and OG, and each was greater when running OG than on the TM, regardless of sex. Shock attenuation was between 66% and 76% for children running under a variety of conditions. Girls had greater peak impact accelerations at the leg and head levels than boys but achieved similar shock attenuation. We do not know how these shock attenuation characteristics are related to overuse injuries.

Ketoconazole attenuates radiation-induction of tumor necrosis factor

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

Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.

1994-07-01

Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2more » inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.« less

Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

PubMed Central

Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

2013-01-01

Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

Coupling of Realistic Rate Estimates with Genomics for Assessing Contaminant Attenuation and Long-Term Plume Containment

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

Colwell, F. S.; Crawford, R. L.; Sorenson, K.

2005-09-01

Acceptance of monitored natural attenuation (MNA) as a preferred treatment technology saves significant site restoration costs for DOE. However, in order to be accepted MNA requires direct evidence of which processes are responsible for the contaminant loss and also the rates of the contaminant loss. Our proposal aims to: 1) provide evidence for one example of MNA, namely the disappearance of the dissolved trichloroethylene (TCE) from the Snake River Plain aquifer (SRPA) at the Idaho National Laboratory’s Test Area North (TAN) site, 2) determine the rates at which aquifer microbes can co-metabolize TCE, and 3) determine whether there are othermore » examples of natural attenuation of chlorinated solvents occurring at DOE sites. To this end, our research has several objectives. First, we have conducted studies to characterize the microbial processes that are likely responsible for the co-metabolic destruction of TCE in the aquifer at TAN (University of Idaho and INL). Second, we are investigating realistic rates of TCE co-metabolism at the low catabolic activities typical of microorganisms existing under aquifer conditions (INL). Using the co-metabolism rate parameters derived in low-growth bioreactors, we will complete the models that predict the time until background levels of TCE are attained in the aquifer at TAN and validate the long-term stewardship of this plume. Coupled with the research on low catabolic activities of co-metabolic microbes we are determining the patterns of functional gene expression by these cells, patterns that may be used to diagnose the co-metabolic activity in the SRPA or other aquifers. Third, we have systematically considered the aquifer contaminants at different locations in plumes at other DOE sites in order to determine whether MNA is a broadly applicable remediation strategy for chlorinated hydrocarbons (North Wind Inc.). Realistic terms for co-metabolism of TCE will provide marked improvements in DOE’s ability to predict

Preoperative Site Marking: Are We Adhering to Good Surgical Practice?

PubMed

Bathla, Sonia; Chadwick, Michael; Nevins, Edward J; Seward, Joanna

2017-06-29

Wrong-site surgery is a never event and a serious, preventable patient safety incident. Within the United Kingdom, national guidance has been issued to minimize the risk of such events. The mandate includes preoperative marking of all surgical patients. This study aimed to quantify regional variation in practice within general surgery and opinions of the surgeons, to help guide the formulation and implementation of a regional general surgery preoperative marking protocol. A SurveyMonkey questionnaire was designed and distributed to 120 surgeons within the Mersey region, United Kingdom. This included all surgical trainees in Mersey (47 registrars, 56 core trainees), 15 consultants, and 2 surgical care practitioners. This sought to ascertain their routine practice and how they would choose to mark for 12 index procedures in general surgery, if mandated to do so. A total of 72 responses (60%) were obtained to the SurveyMonkey questionnaire. Only 26 (36.1%) said that they routinely marked all of their patients preoperatively. The operating surgeon marked the patient in 69% of responses, with the remainder delegating this task. Markings were visible after draping in only 55.6% of marked cases. Based on our findings, surgeons may not be adhering to "Good Surgical Practice"; practice is widely variable and surgeons are largely opposed and resistant to marking patients unless laterality is involved. We suggest that all surgeons need to be actively engaged in the design of local marking protocols to gain support, change practice, and reduce errors.

Variable laser attenuator

DOEpatents

Foltyn, S.R.

1987-05-29

The disclosure relates to low loss, high power variable attenuators comprising one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength. 9 figs.

Melanocortin 4 Receptor Activation Attenuates Mitochondrial Dysfunction in Skeletal Muscle of Diabetic Rats.

PubMed

Zhang, Hao-Hao; Liu, Jiao; Qin, Gui-Jun; Li, Xia-Lian; Du, Pei-Jie; Hao, Xiao; Zhao, Di; Tian, Tian; Wu, Jing; Yun, Meng; Bai, Yan-Hui

2017-11-01

A previous study has confirmed that the central melanocortin system was able to mediate skeletal muscle AMP-activated protein kinase (AMPK) activation in mice fed a high-fat diet, while activation of the AMPK signaling pathway significantly induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor (MC4R) was involved in the development of skeletal muscle injury in diabetic rats. In this study, we treated diabetic rats intracerebroventricularly with MC4R agonist R027-3225 or antagonist SHU9119, respectively. Then, we measured the production of reactive oxygen species (ROS), the levels of malondialdehyde (MDA) and glutathione (GSH), the mitochondrial DNA (mtDNA) content and mitochondrial biogenesis, and the protein levels of p-AMPK, AMPK, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), sirtuin 1 (SIRT1), and manganese superoxide dismutase (MnSOD) in the skeletal muscle of diabetic rats. The results showed that there was significant skeletal muscle injury in the diabetic rats along with serious oxidative stress and decreased mitochondrial biogenesis. Treatment with R027-3225 reduced oxidative stress and induced mitochondrial biogenesis in skeletal muscle, and also activated the AMPK-SIRT1-PGC-1α signaling pathway. However, diabetic rats injected with MC4R antagonist SHU9119 showed an aggravated oxidative stress and mitochondrial dysfunction in skeletal muscle. In conclusion, our results revealed that MC4R activation was able to attenuate oxidative stress and mitochondrial dysfunction in skeletal muscle induced by diabetes partially through activating the AMPK-SIRT1-PGC-1α signaling pathway. J. Cell. Biochem. 118: 4072-4079, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantitative analysis of MRI-guided attenuation correction techniques in time-of-flight brain PET/MRI.

PubMed

Mehranian, Abolfazl; Arabi, Hossein; Zaidi, Habib

2016-04-15

In quantitative PET/MR imaging, attenuation correction (AC) of PET data is markedly challenged by the need of deriving accurate attenuation maps from MR images. A number of strategies have been developed for MRI-guided attenuation correction with different degrees of success. In this work, we compare the quantitative performance of three generic AC methods, including standard 3-class MR segmentation-based, advanced atlas-registration-based and emission-based approaches in the context of brain time-of-flight (TOF) PET/MRI. Fourteen patients referred for diagnostic MRI and (18)F-FDG PET/CT brain scans were included in this comparative study. For each study, PET images were reconstructed using four different attenuation maps derived from CT-based AC (CTAC) serving as reference, standard 3-class MR-segmentation, atlas-registration and emission-based AC methods. To generate 3-class attenuation maps, T1-weighted MRI images were segmented into background air, fat and soft-tissue classes followed by assignment of constant linear attenuation coefficients of 0, 0.0864 and 0.0975 cm(-1) to each class, respectively. A robust atlas-registration based AC method was developed for pseudo-CT generation using local weighted fusion of atlases based on their morphological similarity to target MR images. Our recently proposed MRI-guided maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm was employed to estimate the attenuation map from TOF emission data. The performance of the different AC algorithms in terms of prediction of bones and quantification of PET tracer uptake was objectively evaluated with respect to reference CTAC maps and CTAC-PET images. Qualitative evaluation showed that the MLAA-AC method could sparsely estimate bones and accurately differentiate them from air cavities. It was found that the atlas-AC method can accurately predict bones with variable errors in defining air cavities. Quantitative assessment of bone extraction accuracy based on

Eurasian beaver activity increases water storage, attenuates flow and mitigates diffuse pollution from intensively-managed grasslands.

PubMed

Puttock, Alan; Graham, Hugh A; Cunliffe, Andrew M; Elliott, Mark; Brazier, Richard E

2017-01-15

Beavers are the archetypal keystone species, which can profoundly alter ecosystem structure and function through their ecosystem engineering activity, most notably the building of dams. This can have a major impact upon water resource management, flow regimes and water quality. Previous research has predominantly focused on the activities of North American beaver (Castor canadensis) located in very different environments, to the intensive lowland agricultural landscapes of the United Kingdom and elsewhere in Europe. Two Eurasian beavers (Castor fiber) were introduced to a wooded site, situated on a first order tributary, draining from intensively managed grassland. The site was monitored to understand impacts upon water storage, flow regimes and water quality. Results indicated that beaver activity, primarily via the creation of 13 dams, has increased water storage within the site (holding ca. 1000m 3 in beaver ponds) and beavers were likely to have had a significant flow attenuation impact, as determined from peak discharges (mean 30±19% reduction), total discharges (mean 34±9% reduction) and peak rainfall to peak discharge lag times (mean 29±21% increase) during storm events. Event monitoring of water entering and leaving the site showed lower concentrations of suspended sediment, nitrogen and phosphate leaving the site (e.g. for suspended sediment; average entering site: 112±72mgl -1 , average leaving site: 39±37mgl -1 ). Combined with attenuated flows, this resulted in lower diffuse pollutant loads in water downstream. Conversely, dissolved organic carbon concentrations and loads downstream were higher. These observed changes are argued to be directly attributable to beaver activity at the site which has created a diverse wetland environment, reducing downstream hydrological connectivity. Results have important implications for beaver reintroduction programs which may provide nature based solutions to the catchment-scale water resource management issues

UID...Leaving Its Mark on the Universe

NASA Technical Reports Server (NTRS)

Schramm, Harry F., Jr.

2008-01-01

Since 1975 bar codes on products at the retail counter have been accepted as the standard for entering product identity for price determination. Since the beginning of the 21 st century, the Data Matrix symbol has become accepted as the bar code format that is marked directly on a part, assembly or product that is durable enough to identify that item for its lifetime. NASA began the studies for direct part marking Data Matrix symbols on parts during the Return to Flight activities after the Challenger Accident. Over the 20 year period that has elapsed since Challenger, a mountain of studies, analyses and focused problem solutions developed by and for NASA have brought about world changing results. NASA Technical Standard 6002 and NASA Handbook 6003 for Direct Part Marking Data Matrix Symbols on Aerospace Parts have formed the basis for most other standards on part marking internationally. NASA and its commercial partners have developed numerous products and methods that addressed the difficulties of collecting part identification in aerospace operations. These products enabled the marking of Data Matrix symbols in virtually every situation and the reading of symbols at great distances, severe angles, under paint and in the dark without a light. Even unmarkable delicate parts now have a process to apply a chemical mixture, recently trademarked as Nanocodes, that can be converted to Data Matrix information through software. The accompanying intellectual property is protected by ten patents, several of which are licensed. Direct marking Data Matrix on NASA parts dramatically decreases data entry errors and the number of parts that go through their life cycle unmarked, two major threats to sound configuration management and flight safety. NASA is said to only have people and stuff with information connecting them. Data Matrix is one of the most significant improvements since Challenger to the safety and reliability of that connection.

UID...Now That's Gonna Leave A Mark

NASA Technical Reports Server (NTRS)

Schramm, Harry F., Jr.

2007-01-01

Since 1975 bar codes on products at the retail counter have been accepted as the standard for entering product identity for price determination. Since the beginning of the 21st century, the Data Matrix symbol has become accepted as the bar code format that is marked directly on a part, assembly or product that is durable enough to identify that item for its lifetime. NASA began the studies for direct part marking Data Matrix symbols on parts during the Return to Flight activities after the Challenger Accident. Over the 20 year period that has elapsed since Challenger, a mountain of studies, analyses and focused problem solutions developed by and for NASA have brought about world changing results. NASA Technical Standard 6002 and NASA Handbook 6003 for Direct Part Marking Data Matrix Symbols on Aerospace Parts have formed the basis for most other standards on part marking internationally. NASA and its commercial partners have developed numerous products and methods that addressed the difficulties of collecting part identification in aerospace operations. These products enabled the marking of Data Matrix symbols in virtually every situation and the reading of symbols at great distances, severe angles, under paint and in the dark without a light. Even unmarkable delicate parts now have a process to apply a chemical mixture, recently trademarked as Nanocodes, that can be converted to Data Matrix information through software. The accompanying intellectual property is protected by ten patents, several of which are licensed. Direct marking Data Matrix on NASA parts dramatically decreases data entry errors and the number ofparts that go through their life cycle unmarked, two major threats to sound configuration management and flight safety. NASA is said to only have people and stuff with information connecting them. Data Matrix is one of the most significant improvements since Challenger to the safety and reliability of that connection.

UID...Now That's Gonna Leave a Mark

NASA Technical Reports Server (NTRS)

Schramm, Harry F.

2008-01-01

Since 1975 bar codes on products at the retail counter have been accepted as the standard for entering product identity for price determination. Since the beginning of the 21st century, the Data Matrix symbol has become accepted as the bar code format that is marked directly on a part, assembly or product that is durable enough to identify that item for its lifetime. NASA began the studies for direct part marking Data Matrix symbols on parts during the Return to Flight activities after the Challenger Accident. Over the 20 year period that has elapsed since Challenger, a mountain of studies, analyses and focused problem solutions developed by and for NASA have brought about world changing results. NASA Technical Standard 6002 and NASA Handbook 6003 for Direct Part Marking Data Matrix Symbols on Aerospace Parts have formed the basis for most other standards on part marking internationally. NASA and its commercial partners have developed numerous products and methods that addressed the difficulties of collecting part identification in aerospace operations. These products enabled the marking of Data Matrix symbols in virtually every situation and the reading of symbols at great distances, severe angles, under paint and in the dark without a light. Even unmarkable delicate parts now have a process to apply a chemical mixture, recently trademarked as Nanocodes, that can be converted to Data Matrix information through software. The accompanying intellectual property is protected by ten patents, several of which are licensed. Direct marking Data Matrix on NASA parts dramatically decreases data entry errors and the number of parts that go through their life cycle unmarked, two major threats to sound configuration management and flight safety. NASA is said to only have people and stuff with information connecting them. Data Matrix is one of the most significant improvements since Challenger to the safety and reliability of that connection.

UID....Now That's Gonna Leave A Mark

NASA Technical Reports Server (NTRS)

Schramm, Harry F., Jr.

2008-01-01

Since 1975 bar codes on products at the retail counter have been accepted as the standard for entering product identity for price determination. Since the beginning of the 21 st century, the Data Matrix symbol has become accepted as the bar code format that is marked directly on a part, assembly or product that is durable enough to identify that item for its lifetime. NASA began the studies for direct part marking Data Matrix symbols on parts during the Return to Flight activities after the Challenger Accident. Over the 20 year period that has elapsed since Challenger, a mountain of studies, analyses and focused problem solutions developed by and for NASA have brought about world changing results. NASA Technical Standard 6002 and NASA Handbook 6003 for Direct Part Marking Data Matrix Symbols on Aerospace Parts have formed the basis for most other standards on part marking internationally. NASA and its commercial partners have developed numerous products and methods that addressed the difficulties of collecting part identification in aerospace operations. These products enabled the marking of Data Matrix symbols in virtually every situation and the reading of symbols at great distances, severe angles, under paint and in the dark without a light. Even unmarkable delicate parts now have a process to apply a chemical mixture, recently trademarked as Nanocodes, that can be converted to Data Matrix information through software. The accompanying intellectual property is protected by ten patents, several of which are licensed. Direct marking Data Matrix on NASA parts dramatically decreases data entry errors and the number of parts that go through their life cycle unmarked, two major threats to sound configuration management and flight safety. NASA is said to only have people and stuff with information connecting them. Data Matrix is one of the most significant improvements since Challenger to the safety and reliability of that connection.

Attenuation of MUC4 potentiates the anticancer activity of auranofin via regulation of the Her2/Akt/FOXO3 pathway in ovarian cancer cells.

PubMed

Bae, Jun Sang; Lee, Jongsung; Park, Yoonkook; Park, Kyungmoon; Kim, Jung Ryul; Cho, Dong Hyu; Jang, Kyu Yun; Park, See-Hyoung

2017-10-01

Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus. Notably, auranofin treatment in SKOV3 cells also resulted in the downregulation of the expression levels of both Her2 and phosphorylated Akt. Thus, Her2 was identified as the common molecular target protein by siRNA transfection against MUC4. Western blot analysis of total and nuclear fraction lysates from SKOV3 cells revealed that attenuation of MUC4 combined with auranofin treatment in SKOV3 cells synergistically activated FOXO3 translocation from the cytoplasm to the nucleus through the regulation of the Her2/Akt/FOXO3 pathway. Attenuation of MUC4 by siRNA transfection potentiated the antitumor effect of auranofin which was examined by performing in vitro assays such as WST-1, cell counting, colony formation, TUNEL and Annexin V staining. In addition, western blot analysis of the apoptosis‑related proteins such as PARP1, caspase-3, Bim extra large (EL), Bax and Bcl2 revealed that the attenuation of MUC4 by siRNA transfection potentiates the pro-apoptotic activity of auranofin in SKOV3 cells. Collectively, auranofin could regulate the Her2/Akt/FOXO3 signaling pathway in SKOV3 cells and be used as a potential antitumor agent considering the expression of MUC4 in ovarian cancer patients.

Depressive symptoms and attenuated physiological reactivity to laboratory stressors.

PubMed

Schwerdtfeger, Andreas; Rosenkaimer, Ann-Kathrin

2011-07-01

There is evidence that depressive symptoms are associated with attenuated physiological reactivity to active stressors. However, it is not known whether blunted reactivity in depressed individuals is stressor-specific. We examined cardiovascular and electrodermal reactivity in non-clinical participants with varying levels of depressive symptoms to different active and passive stressors. Depressive symptoms were inversely related to both blood pressure and skin conductance reactivity during a public speaking task and the viewing of the speech video. However, no effects were found during a cold pressor task. Together these findings suggest that depressive symptoms are related to attenuated sympathetic nervous system reactivity in response to self-relevant stressors. Copyright © 2011 Elsevier B.V. All rights reserved.

Marking as Judgment

ERIC Educational Resources Information Center

Brooks, Val

2012-01-01

An aspect of assessment which has received little attention compared with perennial concerns, such as standards or reliability, is the role of judgment in marking. This paper explores marking as an act of judgment, paying particular attention to the nature of judgment and the processes involved. It brings together studies which have explored…

Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

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

Li, Ying; Li, Jia; Li, Shanshan

2015-07-01

Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for themore » suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.« less

9 CFR 316.9 - Products to be marked with official marks.

Code of Federal Regulations, 2010 CFR

2010-01-01

... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

9 CFR 316.9 - Products to be marked with official marks.

Code of Federal Regulations, 2012 CFR

2012-01-01

... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

9 CFR 316.9 - Products to be marked with official marks.

Code of Federal Regulations, 2011 CFR

2011-01-01

... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

9 CFR 316.9 - Products to be marked with official marks.

Code of Federal Regulations, 2014 CFR

2014-01-01

... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

9 CFR 316.9 - Products to be marked with official marks.

Code of Federal Regulations, 2013 CFR

2013-01-01

... marks. 316.9 Section 316.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... liver, beef tongue, and beef heart which has been inspected and passed shall be marked with the official... round, flank, loin, rib, plate, brisket, chuck, and shank are primal parts of beef carcasses. Veal...

The Bionic Clicker Mark I & II.

PubMed

Magee, Elliott G; Ourselin, S; Nikitichev, Daniil; Vercauteren, T; Vanhoestenberghe, Anne

2017-08-14

In this manuscript, we present two 'Bionic Clicker' systems, the first designed to demonstrate electromyography (EMG) based control systems for educational purposes and the second for research purposes. EMG based control systems pick up electrical signals generated by muscle activation and use these as inputs for controllers. EMG controllers are widely used in prosthetics to control limbs. The Mark I (MK I) clicker allows the wearer to change the slide of a presentation by raising their index finger. It is built around a microcontroller and a bio-signals shield. It generated a lot of interest from both the public and research community. The Mark II (MK II) device presented here was designed to be a cheaper, sleeker, and more customizable system that can be easily modified and directly transmit EMG data. It is built using a wireless capable microcontroller and a muscle sensor.

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

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

Cai, Yujun; Li, Jian-Dong; Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatorymore » agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.« less

Attenuation of midinfrared free electron laser energy with eyewear

NASA Astrophysics Data System (ADS)

Joos, Karen M.; Gabella, William

2005-04-01

Purpose: To determine the attenuation of free electron laser (FEL) energy at several wavelengths through microscope objective and eyeglass lenses. Materials and Methods: The FEL at wavelengths of 2.3 um, 2.5 um, 3.0 um, 3.5 um, 4.0 um, 4.5 um, 5.0 um, 6.45 um, 7.0 um, 7.5 um, and 8.0 um was telescoped using a 500 mm nominal focal length lens and a 200 mm focal length lens. The beam had a final spot of about 3 mm and was passed through a 3 mm aperture and onto the 8 mm active area of a J9LP Molectron detector. The eyeglass sample was placed 3 cm in front of the detector. Energy readings were averaged over multiple pulses. Results: Attenuation varied greatly with wavelength and sample from a low attenuation of 0.46 dB, 90% transmission, for short wavelengths through common glass to greater than 60 dB attenuation (transmission at the detector noise level) for IR safe glass by Aura, Inc. Conclusion: Only the designated laser safety goggles effectively attenuate free electron laser energy at 2.3 um and 2.5 um. A microscope objective lens, polycarbonate, and silica glass eyewear is capable of effectively attenuating FEL energy at wavelengths greater than 4.5 um, but the polycarbonate lenses demonstrated material damage.

Attenuated geophysical signatures associated with ongoing remediation efforts at Wurtsmith Air Force Base, Oscoda, Michigan

NASA Astrophysics Data System (ADS)

Che-Alota, V.; Atekwana, E. A.; Sauck, W. A.; Nolan, J. T.; Slater, L. D.

2007-12-01

Previous geophysical investigations (1996, 1997, 2003, and 2004) conducted at the decommissioned Wurtsmith Air Force Base former Fire Training Cell (FT-02) showed a clearly defined high conductivity anomaly associated with hydrocarbon contaminants in the vadose zone and ground water near the source area. The source of the geophysical anomalies was attributed to biogeochemical modifications of the contaminated zone resulting from intrinsic bioremediation. During these previous surveys, ground penetrating radar (GPR) data showed a zone of attenuated GPR reflections extending from the vadose zone to below the water table. Self potential data (SP) data defined a positive anomaly coincident with the hydrochemically defined plume, while electrical resistivity data showed anomalously high conductivity within the zone of impact. In 2007, another integrated geophysical study of the site was conducted. GPR, SP, electrical resistivity, and induced polarization surveys were conducted with expectations of achieving similar results as the past surveys. However, preliminary assessment of the data shows a marked decrease in electrical conductivity and SP response over the plume. GPR data still showed the attenuated signals, but the zone of attenuation was only observed below the water table. We attribute the attenuation of the observed geophysical anomalies to ongoing soil vapor extraction initiated in 2003. Significant removal of the contaminant mass by the vapor extraction system has altered the subsurface biogeochemical conditions and these changes were documented by the 2007 geophysical and geochemical data. The results of this study show that the attenuation of the contaminant plume is detectable with geophysical methods.

Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.

PubMed

Liu, Norika Mengchia; Siu, Kin Lung; Youn, Ji Youn; Cai, Hua

2017-03-01

Restenosis after angioplasty is a serious clinical problem that can result in re-occlusion of the coronary artery. Although current drug-eluting stents have proved to be more effective in reducing restenosis, they have drawbacks of inhibiting reendothelialization to promote thrombosis. New treatment options are in urgent need. We have shown that netrin-1, an axon-guiding protein, promotes angiogenesis and cardioprotection via production of nitric oxide (NO). The present study examined whether and how netrin-1 attenuates neointimal formation in a femoral wire injury model. Infusion of netrin-1 into C57BL/6 mice markedly attenuated neointimal formation following wire injury of femoral arteries, measured by intimal to media ratio (from 1.94 ± 0.55 to 0.45 ± 0.86 at 4 weeks). Proliferation of VSMC in situ was largely reduced. This protective effect was absent in DCC +/- animals. NO production was increased by netrin-1 in both intact and injured femoral arteries, indicating netrin-1 stimulation of endogenous NO production from intact endothelium and remaining endothelial cells post-injury. VSMC migration was abrogated by netrin-1 via a NO/cGMP/p38 MAPK pathway, while timely EPC homing was induced. Injection of netrin-1 preconditioned wild-type EPCs, but not EPCs of DCC +/- animals, substantially attenuated neointimal formation. EPC proliferation, NO production, and resistance to oxidative stress induced apoptosis were augmented by netrin-1 treatment. In conclusion, our data for the first time demonstrate that netrin-1 is highly effective in reducing neointimal formation following vascular endothelial injury, which is dependent on DCC, and attributed to inhibition of VSMC proliferation and migration, as well as improved EPC function. These data may support usage of netrin-1 and netrin-1 preconditioned EPCs as novel therapies for post angioplasty restenosis. Netrin-1 attenuates neointimal formation following post endothelial injury via DCC and NO. Netrin-1 inhibits

Ultrasonic attenuation in pearlitic steel.

PubMed

Du, Hualong; Turner, Joseph A

2014-03-01

Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes. Copyright © 2013 Elsevier B.V. All rights reserved.

LINE-ABOVE-GROUND ATTENUATOR

DOEpatents

Wilds, R.B.; Ames, J.R.

1957-09-24

The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

Compound K Attenuates the Development of Atherosclerosis in ApoE−/− Mice via LXRα Activation

PubMed Central

Zhou, Li; Zheng, Yu; Li, Zhuoying; Bao, Lingxia; Dou, Yin; Tang, Yuan; Zhang, Jianxiang; Zhou, Jianzhi; Liu, Ya; Jia, Yi; Li, Xiaohui

2016-01-01

Background: Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti-antherosclerosis roles of compound K. Methods: We treated the atherosclerotic model animals (apoE−/− mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments. Results: Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRα may contribute to the athero-protective effects of compound K. Conclusion: These observations provide evidence for an athero-protective effect of compound K via LXRα activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis. PMID:27399689

Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

PubMed Central

Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

2006-01-01

Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells. PMID:16651609

Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

PubMed

Quan-Jun, Yang; Yan, Huo; Yong-Long, Han; Li-Li, Wan; Jie, Li; Jin-Lu, Huang; Jin, Lu; Peng-Guo, Chen; Run, Gan; Cheng, Guo

2017-02-01

Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence

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

Zheng, H.; Crowley, J.J.; Chan, J.C.

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents thatmore » attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.« less

Attenuator And Conditioner

DOEpatents

Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

2006-04-04

An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

49 CFR 221.13 - Marking device display.

Code of Federal Regulations, 2010 CFR

2010-10-01

... visibility that the end silhouette of a standard box car cannot be seen from 1/2 mile on tangent track by a... with, (2) display on the trailing end of the rear car of that train, and (3) continuously illuminate or... cell activation mechanism complying with paragraph (c) of this section, the marking devices prescribed...

Attenuation - The Ugly Stepsister of Velocity in the Noise Correlation Family

NASA Astrophysics Data System (ADS)

Lawrence, J. F.; Prieto, G.; Denolle, M.; Seats, K. J.

2012-12-01

Noise correlation functions and noise transfer functions have shown in practice to preserve the relative amplitude information, despite the challenge to reliably resolve it compared to phase information. Yet amplitude contains important information about wavefield interactions with the subsurface structure, including focusing/defocusing and seismic attenuation. To focus on the anelastic effects, or attenuation, we measure amplitude decay with increased station separation (distance). We present numerical results showing that the noise correlation functions (NCFs) preserve the relative amplitude information and properly retrieve seismic attenuation for sufficient noise source distribution and appropriate processing. Attenuation is only preserved through the relative decay of distinct waves from multiple simultaneous source locations. With appropriate whitening (and no time domain normalization), the coherency preserves correlation amplitudes proportional to the relative decay expected with all the inter-station spacing. We present new attenuation results for the United States, and particularly the Yellowstone region that illustrate lateral variations that strongly correlate with known geological features such as sedimentary basins, crustal blocks and active volcanism.

β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia.

PubMed

Aversa, Zaira; Bonetto, Andrea; Costelli, Paola; Minero, Valerio Giacomo; Penna, Fabio; Baccino, Francesco Maria; Lucia, Simone; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

2011-03-01

β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMB-enriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2α, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2α markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2α levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.

Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats.

PubMed

Zhang, Juan; Tucker, Lorelei Donovan; DongYan; Lu, Yujiao; Yang, Luodan; Wu, Chongyun; Li, Yong; Zhang, Quanguang

2018-06-01

Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

Pavement marking performance analysis

DOT National Transportation Integrated Search

2009-06-30

This research evaluated pavement marking performance and developed useful degradation models for thermoplastic : and paint pavement markings which can help North Carolina meet the pending FHWA minimum retroreflectivity : requirements. The impacts of ...

The Bionic Clicker Mark I & II

PubMed Central

Magee, Elliott G.; Ourselin, S.; Nikitichev, Daniil; Vercauteren, T.; Vanhoestenberghe, Anne

2017-01-01

In this manuscript, we present two 'Bionic Clicker' systems, the first designed to demonstrate electromyography (EMG) based control systems for educational purposes and the second for research purposes. EMG based control systems pick up electrical signals generated by muscle activation and use these as inputs for controllers. EMG controllers are widely used in prosthetics to control limbs. The Mark I (MK I) clicker allows the wearer to change the slide of a presentation by raising their index finger. It is built around a microcontroller and a bio-signals shield. It generated a lot of interest from both the public and research community. The Mark II (MK II) device presented here was designed to be a cheaper, sleeker, and more customizable system that can be easily modified and directly transmit EMG data. It is built using a wireless capable microcontroller and a muscle sensor. PMID:28829413

GCF Mark IV development

NASA Technical Reports Server (NTRS)

Mortensen, L. O.

1982-01-01

The Mark IV ground communication facility (GCF) as it is implemented to support the network consolidation program is reviewed. Changes in the GCF are made in the area of increased capacity. Common carrier circuits are the medium for data transfer. The message multiplexing in the Mark IV era differs from the Mark III era, in that all multiplexing is done in a GCF computer under GCF software control, which is similar to the multiplexing currently done in the high speed data subsystem.

Korean Red Ginseng Saponin Fraction Rich in Ginsenoside-Rb1, Rc and Rb2 Attenuates the Severity of Mouse Collagen-Induced Arthritis

PubMed Central

Endale, Mehari; Im, Eun Ju; Lee, Joo Young; Kim, Sung Dae; Song, Yong-Bum; Kwak, Yi-Seong; Kim, Chaekyun; Kim, Seung-Hyung; Roh, Seong-Soo; Rhee, Man Hee

2014-01-01

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3+/CD69+, CD4+/CD25+, CD8+ T-cell, CD19+, B220/CD23+ B-cell, MHCII+/CD11c+, and Gr-1+/CD11b+ cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice. PMID:24833816

Muscarinic receptor stimulation of D-aspartate uptake into human SH-SY5Y neuroblastoma cells is attenuated by hypoosmolarity.

PubMed

Foster, Daniel J; Heacock, Anne M; Fisher, Stephen K

2010-04-01

In addition to its function as an excitatory neurotransmitter, glutamate plays a major role as an osmolyte within the central nervous system (CNS). Accordingly, mechanisms that regulate glutamate release and uptake are of physiological importance not only during conditions in which cell volume remains constant but also when cells are subjected to hypoosmotic stress. In the present study, the ability of muscarinic cholinergic receptors (mAChRs) to regulate the uptake of glutamate (monitored as D-aspartate) into human SH-SY5Y neuroblastoma cells under isotonic or hypotonic conditions has been examined. In isotonic media, agonist activation of mAChRs resulted in a significant increase (250-300% of control) in the uptake of D-aspartate and, concurrently, a cellular redistribution of the excitatory amino acid transporter 3 (EAAT3) to the plasma membrane. mAChR-mediated increases in d-aspartate uptake were potently blocked by the EAAT3 inhibitor l-beta-threo-benzyl-aspartate. In hypotonic media, the ability of mAChR activation to facilitate D-aspartate uptake was significantly attenuated (40-50%), and the cellular distribution of EAAT3 was disrupted. Reduction of mAChR-stimulated D-aspartate uptake under hypoosmotic conditions could be fully reversed upon re-exposure of the cells to isotonic media. Under both isotonic and hypotonic conditions, mAChR-mediated increases in D-aspartate uptake depended on cytoskeletal integrity, protein kinase C and phosphatidylinositol 3-kinase activities, and the availability of intracellular Ca2+. In contrast, dependence on extracellular Ca2+ was observed only under isotonic conditions. The results suggest that, although the uptake of D-aspartate into SH-SY5Y cells is enhanced after mAChR activation, this process is markedly attenuated by hypoosmolarity.

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

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

Genz, Berit; Thomas, Maria; Pützer, Brigitte M.

2014-11-01

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluatedmore » an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells.« less

Fucoxanthin enhances HO-1 and NQO1 expression in murine hepatic BNL CL.2 cells through activation of the Nrf2/ARE system partially by its pro-oxidant activity.

PubMed

Liu, Cheng-Ling; Chiu, Yu-Ting; Hu, Miao-Lin

2011-10-26

To determine whether fucoxanthin, a major carotenoid in brown sea algae, may activate cellular antioxidant enzymes via up-regulation of the Nrf2/antioxidant-response element (ARE) pathway, we incubated mouse hepatic BNL CL.2 cells with fucoxanthin (0.5-20 μM) for 0-24 h. We found that fucoxanthin (≥5 μM) significantly increased cellular reactive oxygen species (ROS) at 6 h of incubation, whereas preincubation with α-d-tocopherol (30 μM) significantly attenuated the increase of ROS, indicating the pro-oxidant nature of fucoxanthin. Fucoxanthin significantly increased the phosphorylation of ERK and p38 and markedly increased nuclear Nrf2 protein accumulation after incubation for 12 h. Moreover, fucoxanthin significantly enhanced binding activities of nuclear Nrf2 with ARE and increased mRNA and protein expression of HO-1 and NQO1 after incubation for 12 h. siRNA inhibition of Nrf2 led to markedly decreased HO-1 and NQO1 protein expression. Thus, fucoxanthin may exert its antioxidant activity, at least partly, through its pro-oxidant actions.

RANK-c attenuates aggressive properties of ER-negative breast cancer by inhibiting NF-κB activation and EGFR signaling.

PubMed

Sirinian, Chaido; Papanastasiou, Anastasios D; Schizas, Michail; Spella, Magda; Stathopoulos, Georgios T; Repanti, Maria; Zarkadis, Ioannis K; King, Tari A; Kalofonos, Haralabos P

2018-05-29

The RANK/RANKL axis emerges as a key regulator of breast cancer initiation, progression, and metastasis. RANK-c is a RANK receptor isoform produced through alternative splicing of the TNFRSF11A (RANK) gene and a dominant-negative regulator of RANK-induced nuclear factor-κB (NF-κB) activation. Here we report that RANK-c transcript is expressed in 3.2% of cases in The Cancer Genome Atlas breast cancer cohort evenly between ER-positive and ER-negative cases. Nevertheless, the ratio of RANK to RANK-c (RANK/RANK-c) is increased in ER-negative breast cancer cell lines compared to ER-positive breast cancer cell lines. In addition, forced expression of RANK-c in ER-negative breast cancer cell lines inhibited stimuli-induced NF-κB activation and attenuated migration, invasion, colony formation, and adhesion of cancer cells. Further, RANK-c expression in MDA-MB-231 cells inhibited lung metastasis and colonization in vivo. The RANK-c-mediated inhibition of cancer cell aggressiveness and nuclear factor-κB (NF-κB) activation in breast cancer cells seems to rely on a RANK-c/TNF receptor-associated factor-2 (TRAF2) protein interaction. This was further confirmed by a mutated RANK-c that is unable to interact with TRAF2 and abolishes the ability to attenuate NF-κB activation, migration, and invasion. Additional protein interaction characterization revealed epidermal growth factor receptor (EGFR) as a novel interacting partner for RANK-c in breast cancer cells with a negative effect on EGFR phosphorylation and EGF-dependent downstream signaling pathway activation. Our findings further elucidate the complex molecular biology of the RANKL/RANK system in breast cancer and provide preliminary data for RANK-c as a possible marker for disease progression and aggressiveness.

Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors

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

Katz, Jason D.; Haidle, Andrew; Childers, Kaleen K.

2017-01-01

The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer’s disease.

Postnatal growth hormone deficiency in growing rats causes marked decline in the activity of spinal cord acetylcholinesterase but not butyrylcholinesterase.

PubMed

Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail

2012-11-01

The effects of growth hormone (GH) deficiency on the developmental changes in the abundance and activity of cholinesterase enzymes were studied in the developing spinal cord (SC) of postnatal rats by measuring the specific activity of acetylcholinesterase (AChE), a marker for cholinergic neurons and their synaptic compartments, and butyrylcholinesterase (BuChE), a marker for glial cells and neurovascular cells. Specific activities of these two enzymes were measured in SC tissue of 21- and 90 day-old (P21, weaning age; P90, young adulthood) GH deficient spontaneous dwarf (SpDwf) mutant rats which lack anterior pituitary and circulating plasma GH, and were compared with SC tissue of normal age-matched control animals. Assays were carried out for AChE and BuChE activity in the presence of their specific chemical inhibitors, BW284C51 and iso-OMPA, respectively. Results revealed that mean AChE activity was markedly and significantly reduced [28% at P21, 49% at P90, (p<0.01)] in the SC of GH deficient rats compared to age-matched controls. GH deficiency had a higher and more significant effect on AChE activity of the older (P90) rats than the younger ones (P21) ones. In contrast, BuChE activity in SC showed no significant changes in GH deficient rats at either of the two ages studied. Results imply that, in the absence of pituitary GH, the postnatal proliferation of cholinergic synapses in the rat SC, a CNS structure, where AChE activity is abundant, is markedly reduced during both the pre- and postweaning periods; more so in the postweaning than preweaning ages. In contrast, the absence of any effects on BuChE activity implies that GH does not affect the development of non-neuronal elements, e.g., glia, as much as the neuronal and synaptic compartments of the developing rat SC. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Foley, C. M.; Schadt, J. C.; Laughlin, M. H.; Hasser, E. M.

1998-01-01

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

Human thioredoxin-1 attenuates the rate of lipopolysaccharide-induced preterm delivery in mice in association with its anti-inflammatory effect.

PubMed

Namba, Fumihiko; Kobayashi-Miura, Mikiko; Goda, Taro; Nakura, Yukiko; Nishiumi, Fumiko; Son, Aoi; Kubota, Akio; Yodoi, Junji; Yanagihara, Itaru

2016-09-01

Maternal intrauterine infection/inflammation represents the major etiology of preterm delivery and the leading cause of neonatal mortality and morbidity. The aim of this study was to investigate the anti-inflammatory properties of thioredoxin-1 in vivo and its potential ability to attenuate the rate of inflammation-induced preterm delivery. Two intraperitoneal injections of lipopolysaccharide from Escherichia coli were administered in pregnant mice on gestational day 15, with a 3-h interval between the injections. From either 1 h before or 1 h after the first lipopolysaccharide injection, mice received three intravenous injections of either recombinant human thioredoxin-1, ovalbumin, or vehicle, with a 3-h interval between injections. Intraperitoneal injection of lipopolysaccharide induced a rise of tumor necrosis factor-α, interferon-γ, monocyte chemotactic protein 1, and interleukin-6 in maternal serum levels and provoked preterm delivery. Recombinant human thoredoxin-1 prevented the rise in these proinflammatory cytokine levels. After the inflammatory challenge, placentas exhibited severe maternal vascular dilatation and congestion and a marked decidual neutrophil activation. These placental pathological findings were ameliorated by recombinant human thioredoxin-1, and the rate of inflammation-induced preterm delivery was attenuated. Thioredoxin-1 may thus represent a novel effective treatment to delay inflammation-induced preterm delivery.

Overactivation of Mitogen-Activated Protein Kinase and Suppression of Mitofusin-2 Expression Are Two Independent Events in High Mobility Group Box 1 Protein–Mediated T Cell Immune Dysfunction

PubMed Central

Tang, Lu-ming; Zhao, Guang-ju; Zhu, Xiao-mei; Dong, Ning; Yu, Yan

2013-01-01

High mobility group box 1 protein (HMGB1), a critical proinflammatory cytokine, has recently been identified to be an immunostimulatory signal involved in sepsis-related immune dysfunction when released extracellularly, but the potential mechanism involved remains elusive. Here, we showed that the treatment with HMGB1 in vitro inhibited T lymphocyte immune response and expression of mitofusin-2 (Mfn-2; a member of the mitofusin family) in a dose- and time-dependent manner. Upregulation of Mfn-2 expression attenuated the suppressive effect of HMGB1 on T cell immune function. The phosphorylation of both extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) was markedly upregulated by treating with high amount of HMGB1, while pretreatment with ERK1/2 and p38 MAPK-specific inhibitors (U0126 and SB203580) could attenuate suppression of T cell immune function and nuclear factor of activated T cell (NFAT) activation induced by HMGB1, respectively. HMGB1-induced activity of ERK1/2 and p38 was not fully inhibited in the presence of U0126 or SB203580. Interestingly, overexpression of Mfn-2 had no marked effect on HMGB1-mediated activation of MAPK, but could attenuate the suppressive effect of HMGB1 on the activity of NFAT. Thus, the mechanisms involved in HMGB1-induced T cell immune dysfunction in vitro at least partly include suppression of Mfn-2 expression, overactivation of ERK1/2, p38 MAPK, and intervention of NFAT activation, while the protective effect of Mfn-2 on T cell immune dysfunction induced by HMGB1 is dependent on other signaling pathway associated with NFAT, but not MAPK. Taken together, we conclude that overactivation of MAPK and suppression of Mfn-2 expression are two independent events in HMGB1-mediated T cell immune dysfunction. PMID:23697559

Calpain Inhibition Attenuates Angiotensin II-induced Abdominal Aortic Aneurysms and Atherosclerosis in LDL Receptor Deficient Mice

PubMed Central

Subramanian, Venkateswaran; Uchida, Haruhito Adam; Ijaz, Talha; Moorleghen, Jessica J.; Howatt, Deborah A.; Balakrishnan, Anju

2011-01-01

Chronic infusion of angiotensin II (AngII) augments atherosclerosis and abdominal aortic aneurysm (AAAs) formation in hypercholesterolemic mice. AngII-induced AAAs are associated with medial macrophage accumulation and matrix metalloproteinase (MMP) activation. Inhibition of calpain, a calcium-activated neutral cysteine protease, by overexpression of its endogenous inhibitor, calpastatin, attenuates AngII-induced leukocyte infiltration, perivascular inflammation, and MMP activation in mice. The purpose of this study was to define whether pharmacological inhibition of calpain influences AngII-induced AAAs in hypercholesterolemic mice. Male LDL receptor −/− mice were fed a fat-enriched diet and administered with either vehicle or a calpain-specific inhibitor, BDA-410 (30 mg/kg/day) for 5 weeks. After 1 week of feeding, mice were infused with AngII (1,000 ng/kg/min) for 4 weeks. AngII-infusion profoundly increased aortic calpain protein and activity. BDA-410 administration had no effect on plasma cholesterol concentrations or AngII-increased systolic blood pressure. Calpain inhibition significantly attenuated AngII-induced AAA formation and atherosclerosis development. BDA-410 administration attenuated activation of MMP12, pro-inflammatory cytokines (IL-6, MCP-1) and macrophage infiltration into the aorta. BDA-410 administration significantly attenuated thioglycollate-elicited macrophage accumulation in the peritoneal cavity. We conclude that calpain inhibition using BDA-410 attenuated AngII-induced AAA formation and atherosclerosis development in LDL receptor −/− mice. PMID:21964156

RADIO FREQUENCY ATTENUATOR

DOEpatents

Giordano, S.

1963-11-12

A high peak power level r-f attenuator that is readily and easily insertable along a coaxial cable having an inner conductor and an outer annular conductor without breaking the ends thereof is presented. Spaced first and second flares in the outer conductor face each other with a slidable cylindrical outer conductor portion therebetween. Dielectric means, such as water, contact the cable between the flares to attenuate the radio-frequency energy received thereby. The cylindrical outer conductor portion is slidable to adjust the voltage standing wave ratio to a low level, and one of the flares is slidable to adjust the attenuation level. An integral dielectric container is also provided. (AFC)

The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.

PubMed

Waumans, Yannick; Vliegen, Gwendolyn; Maes, Lynn; Rombouts, Miche; Declerck, Ken; Van Der Veken, Pieter; Vanden Berghe, Wim; De Meyer, Guido R Y; Schrijvers, Dorien; De Meester, Ingrid

2016-02-01

Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

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

Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated proteinmore » kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free

Hydrogen-Rich Saline Inhibits NLRP3 Inflammasome Activation and Attenuates Experimental Acute Pancreatitis in Mice

PubMed Central

Ma, Jie; Jin, Wei-Hua; Wu, Juan; Fan, Kai-Hua

2014-01-01

Increasing evidence has demonstrated that reactive oxygen species (ROS) induces oxidative stress and plays a crucial role in the pathogenesis of acute pancreatitis (AP). Hydrogen-rich saline (HRS), a well-known ROS scavenger, has been shown to possess therapeutic benefit on AP in many animal experiments. Recent findings have indicated that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, an intracellular multiprotein complex required for the maturation of interleukin- (IL-) 1β, may probably be a potential target of HRS in the treatment of AP. Therefore, in this study, we evaluated the activation of NLRP3 inflammasome and meanwhile assessed the degree of oxidative stress and inflammatory cascades, as well as the histological alterations in mice suffering from cerulein-induced AP after the treatment of HRS. The results showed that the activation of NLRP3 inflammasome in AP mice was substantially inhibited following the administration of HRS, which was paralleled with the decreased NF-κB activity and cytokines production, attenuated oxidative stress and the amelioration of pancreatic tissue damage. In conclusion, our study has, for the first time, revealed that inhibition of the activation of NLRP3 inflammasome probably contributed to the therapeutic potential of HRS in AP. PMID:25214720

49 CFR 172.304 - Marking requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Marking requirements. 172.304 Section 172.304 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SECURITY PLANS Marking § 172.304 Marking requirements. (a) The marking required in this subpart— (1) Must...

Stretch-activated ion channel blockade attenuates adaptations to eccentric exercise.

PubMed

Butterfield, Timothy A; Best, Thomas M

2009-02-01

The purpose of this study was to test the hypothesis that stretch-activated ion channel (SAC) function is essential for the repeated bout effect (RBE) in skeletal muscle. Specifically, we investigated if daily injections of streptomycin (a known SAC blocker) would abrogate the muscle's adaptive resistance to the damaging effects of eccentric exercise over a 4-wk period. Furthermore, we hypothesized that the lack of an RBE would be due to the lack of functional adaptations that typically result from repeated bouts of eccentric exercise, including increased peak isometric torque, muscle hypertrophy, and rightward shift of the torque-angle relationship. Twelve New Zealand white rabbits were each subjected to 12 bouts of eccentric exercise over a 4-wk period while receiving either daily injections of streptomycin or sham injections. Although blocking the SAC function completely eliminated the expected adaptive response in biomechanical parameters during the exercise regimen, there remained evidence of an acquired RBE, albeit with an attenuated response when compared with the muscles with intact SAC function. Blocking sarcolemmal SAC eliminates functional adaptations of muscle after eccentric exercise. In the absence of SAC function, muscles subjected to chronic eccentric exercise still exhibit some degree of the RBE. As such, it appears that the signaling cascade that results in functional, biomechanical adaptations associated with the RBE during eccentric exercise is dependent upon intact SAC function.

Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

PubMed Central

Xiang, Hong; Zhang, Qingkai; Qi, Bing; Tao, Xufeng; Xia, Shilin; Song, Huiyi; Qu, Jialin; Shang, Dong

2017-01-01

Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP. PMID:28487653

A benzenediamine derivative fc-99 attenuates lupus-like syndrome in MRL/lpr mice related to suppression of pDC activation.

PubMed

Ji, Jianjian; Fan, Hongye; Li, Fanlin; Li, Xiaojing; Dong, Guanjun; Gong, Wei; Song, Yuxian; Liu, Fei; Hua, Chunyan; Tan, Renxiang; Dou, Huan; Hou, Yayi

2015-12-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with prominent chronic inflammatory aspects. Plasmacytoid dendritic cells (pDCs), which are the principal interferon-α (IFN-α)-producing cells, have known to be critically involved in SLE pathogenesis. Our previous research demonstrated that a benzenediamine derivative FC-99 possessed anti-inflammatory activities. However, the effects of FC-99 on SLE have not been investigated to date. In this study, we found that FC-99 attenuated lupus-like pathological symptoms and lupus nephritis as well as the expression of pro-inflammatory cytokines in kidneys of MRL/lpr mice. FC-99 also decreased both the total IgM, total IgG and anti-dsDNA IgG levels in sera and the activation of B cells in the PBMCs and spleens of MRL/lpr mice. Moreover, FC-99 inhibited the abnormal activation and number of pDCs from PBMCs and spleens and levels of IFN-α in MRL/lpr mice. Notably, FC-99 significantly suppressed the expression of IFN-inducible genes in peripheral blood mononuclear cells (PBMCs) and spleens from MRL/lpr mice. As expected, in vitro experiments demonstrated that FC-99 decreased both the activation and IFN-α production of pDCs and inhibited IRAK4 phosphorylation in pDCs upon TLR7 and TLR9 stimulation. We further confirm that the inhibition of FC-99 on B cell activation depended on level of pDCs-secreting IFN-α. These data indicate that FC-99 attenuated lupus-like syndrome in MRL/lpr mice related to suppression of pDC activation, especially pDCs-secreting IFN-α. This study suggests that FC-99 may be a potential therapeutic candidate for the treatment of SLE. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Classroom Mark-Recapture with Crickets

ERIC Educational Resources Information Center

Whiteley, Andrew R.; Woolfe, Jennifer; Kennedy, Kathleen; Oberbillig, David; Brewer, Carol

2007-01-01

Mark-recapture techniques are commonly used by ecologists to estimate abundance of naturally occurring animals and are an important component of ecology curricula. This investigation teaches a mark-recapture technique using store-bought crickets in 10-gallon aquaria and provides an inexpensive way to teach students about mark-recapture in a real…

Combined subchronic fluoride-lead intoxication and its attenuation with the help of a complex of bioprotectors.

PubMed

Katsnelson, B A; Privalova, L I; Kireyeva, Y P; Yeremenko, O S; Sutunkova, M P; Valamina, I E; Varaksin, A N; Panov, V G; Kazmer, J I

2012-01-01

Combined toxicity of lead and fluoride has been studied insufficiently, and there is no known information about attempts to inhibit it with any bioprotectors. Lead acetate and sodium fluoride, administered separately or in combination, were injected i.p. to rats at isoeffective sublethal doses 3 times a week for 6 weeks. Some of the rats were exposed to the same combination against the background of oral administration of a bioprotector complex (BPC) comprising pectin, glutamate, and multivitamin/multimineral preparations. Following exposure, functional and biochemical indices and histopathological examinations of the femur of exposed and control rats were evaluated for signs of toxicity. We have shown that with regard to a number of effects on the organism level the combined toxicity of lead and fluoride may be evaluated as additive or even superadditive, but lead reduces fluoride accumulation in the bone, and pathological changes in the bone tissue proved to be less marked for combined exposure compared with separate exposures. The BPC has been demonstrated to attenuate a range of the combined harmful effects of lead and fluoride, including those on the bone tissue. In spite of the fact that fluoride and lead may reciprocally attenuate their harmful effects on the bone tissue in case of combined exposure, they prove to be more toxic for soft tissues just in combination than when administered separately. The development of combined intoxication may be substantially inhibited by means of the tested set of innocuous biologically active agents.

Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

PubMed Central

Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

2015-01-01

Abstract Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32–36 weeks) pregnancy, and post-partum (6–10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min−1 and 16 ± 5 vs. 30 ± 3 bursts min−1 in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min−1 at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal–adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy. Key points Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian

Activated protein C attenuates systemic lupus erythematosus and lupus nephritis in MRL-Fas(lpr) mice.

PubMed

Lichtnekert, Julia; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Darisipudi, Murthy Narayana; Allam, Ramanjaneyulu; Anders, Hans-Joachim

2011-09-15

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current treatments including steroids, antimalarials, and immunosuppressive drugs have significant side effects. Activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version has been approved by the U.S. Food and Drug Administration to treat severe sepsis. Given the similarities between overshooting immune activation in sepsis and autoimmunity, we hypothesized that recombinant activated protein C would also suppress SLE and lupus nephritis. To test this concept, autoimmune female MRL-Fas(lpr) mice were injected with either vehicle or recombinant human activated protein C from week 14-18 of age. Activated protein C treatment significantly suppressed lupus nephritis as evidenced by decrease in activity index, glomerular IgG and complement C3 deposits, macrophage counts, as well as intrarenal IL-12 expression. Further, activated protein C attenuated cutaneous lupus and lung disease as compared with vehicle-treated MRL-Fas(lpr) mice. In addition, parameters of systemic autoimmunity, such as plasma cytokine levels of IL-12p40, IL-6, and CCL2/MCP-1, and numbers of B cells and plasma cells in spleen were suppressed by activated protein C. The latter was associated with lower total plasma IgM and IgG levels as well as lower titers of anti-dsDNA IgG and rheumatoid factor. Together, recombinant activated protein C suppresses the abnormal systemic immune activation in SLE of MRL-Fas(lpr) mice, which prevents subsequent kidney, lung, and skin disease. These results implicate that recombinant activated protein C might be useful for the treatment of human SLE.

Biochemical Basis of Sestrin Physiological Activities

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

Ho, Allison; Cho, Chun-Seok; Namkoong, Sim

Excessive accumulation of reactive oxygen species (ROS) and chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are well-characterized promoters of aging and age-associated degenerative pathologies. Sestrins, a family of highly conserved stress-inducible proteins, are important negative regulators of both ROS and mTORC1 signaling pathways; however, the mechanistic basis of how Sestrins suppress these pathways remains elusive. In the past couple of years, breakthrough discoveries about Sestrin signaling and its molecular nature have markedly increased our biochemical understanding of Sestrin function. These discoveries have also uncovered new potential therapeutic strategies that may eventually enable us to attenuate agingmore » and age-associated diseases.« less

A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers.

PubMed

Sugino, N; Kawahara, M; Tatsumi, G; Kanai, A; Matsui, H; Yamamoto, R; Nagai, Y; Fujii, S; Shimazu, Y; Hishizawa, M; Inaba, T; Andoh, A; Suzuki, T; Takaori-Kondo, A

2017-11-01

Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDSs) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells. NCD38 elevated H3K27ac level on enhancers of these LSD1 signature genes and newly activated ~500 super-enhancers. Upregulated genes with super-enhancer activation in erythroleukemia cells were enriched in leukocyte differentiation. Eleven genes including GFI1 and ERG, but not CEBPA, were identified as the LSD1 signature with super-enhancer activation. Super-enhancers of these genes were activated prior to induction of the transcripts and myeloid differentiation. Depletion of GFI1 attenuated myeloid differentiation by NCD38. Finally, a single administration of NCD38 causes the in vivo eradication of primary MDS-related leukemia cells with a complex karyotype. Together, NCD38 derepresses super-enhancers of hematopoietic regulators that are silenced abnormally by LSD1, attenuates leukemogenic programs and consequently exerts anti-leukemic effect against MDS-related leukemia with adverse outcome.

Reserve-building activities attenuate treatment burden in chronic illness: The mediating role of appraisal and social support

PubMed Central

Schwartz, Carolyn E; Zhang, Jie; Michael, Wesley; Eton, David T; Rapkin, Bruce D

2018-01-01

This study examines the importance of four psychosocial factors—personality, cognitive appraisal of quality of life, social support, and current reserve-building—in predicting treatment burden in chronically ill patients. Chronically ill patients (n = 446) completed web-based measures. Structural equation modeling was used to investigate psychosocial factors predicting treatment burden. Reserve-building activities indirectly reduced treatment burden by: (1) reducing health worries appraisals, (2) reducing financial difficulties, (3) increasing calm and peaceful appraisals, and (4) increasing perceived social support. These findings point to key behaviors that chronically ill people can use to attenuate their treatment burden. PMID:29785278

Dietary calcein marking of shovelnose sturgeon and the effect of sunlight on mark retention

USGS Publications Warehouse

Honeyfield, D.C.; Kindschi, G.A.; Bell, T.A.; Mohler, J.W.

2011-01-01

Calcein, a fluorochrome dye, is a potential fish-marking agent that has not been evaluated in sturgeon. Shovelnose sturgeon Scaphirhynchus platorynchus (average weight, 9.7 g) were fed calcein, immersed in a calcein bath, or left unmarked to determine calcein mark intensity. In the first study, six treatments were evaluated in a two-by-three factorial arrangement. Feed was formulated with 2.0 g of SE-MARK/kg either as powder or in an encapsulated form. Sturgeon were fed the test diets for 5, 10, or 15 d. They readily ate feed containing powdered or encapsulated calcein. Sturgeon fed powdered calcein had more brilliant marks than those fed encapsulated calcein (8.27 versus 4.66 lm; P < 0.03) 6 months postexposure. Fish fed calcein for 15 d (11.26 lm) were more brilliant (P < 0.002) than fish fed for either 5 d (3.02 lm) or 10 d (5.11 lm). Post hoc comparison of the three treatment groups showed that sturgeon fed powdered calcein for 15 d (14.06 lm) were brighter (P < 0.01) than fish fed encapsulated calcein (8.46 lm) or fish immersed in calcein (9.68 lm). In the second study, previouslymarked sturgeon were exposed to sunlight for 14months to determine their retention of calcein marks. Dorsal marks were no longer visible on fish exposed to 100% sunlight after 8 weeks. Most but not all fish exposed to 20% sunlight had no discernable dorsalmarks after 8 weeks, but ventral marks at the pectoral fin girdle were present on all fish in the 0% and 20% sunlight exposure treatments. Feeding calcein for 15 d appears to have excellent potential for practical application, such as distinguishing hatchery-reared from wild fish. Ventral calcein marks remained visible after 14 months of exposure to 20% sunlight when sturgeon were reared in clear water. ?? American Fisheries Society 2011.

46 CFR 185.602 - Hull markings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 185.602 Section 185.602 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Markings Required § 185.602 Hull markings. (a) Each vessel must be marked as required by part 67...

Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

PubMed

Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

2012-11-01

Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

14 CFR 23.1555 - Control markings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 23.1555 Section 23.1555...

14 CFR 23.1555 - Control markings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 23.1555 Section 23.1555...

14 CFR 23.1555 - Control markings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 23.1555 Section 23.1555...

14 CFR 23.1555 - Control markings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 23.1555 Section 23.1555... Markings and Placards § 23.1555 Control markings. (a) Each cockpit control, other than primary flight controls and simple push button type starter switches, must be plainly marked as to its function and method...

Anti-inflammatory activity of Heliotropium strigosum in animal models.

PubMed

Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

2015-12-01

The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models. © The Author(s) 2012.

Identification of active compounds from Aurantii Immatri Pericarpium attenuating brain injury in a rat model of ischemia-reperfusion.

PubMed

Yang, Eun-Ju; Lim, Sun Ha; Song, Kyung-Sik; Han, Hyung Soo; Lee, Jongwon

2013-05-01

Ischemic stroke is caused by brain injury due to prolonged ischemia by occlusion of cerebral arteries. In this study, we isolated active compounds from an ethanol extract of Aurantii Immatri Pericarpium (HY5356). We first showed by DNA fragmentation assay that HY5356 improved human hepatocellular carcinoma cells (HepG2) under hypoxic conditions by inhibiting apoptosis. When HY5356 was fractionated with dichloromethane (MC), ethyl acetate (EA) and n-butanol (BU), the MC fraction improved cell viability at the lowest concentration (100 μg/ml). Intraperitoneal injection of HY5356 (200 mg/kg) or the MC fraction (200 mg/kg) to rats prior to occlusion attenuated brain injury significantly in a rat model of ischemia-reperfusion. Adopting cell viability under hypoxic conditions as an activity screening system, we isolated nobiletin and tangeretin as active compounds. The results suggest that intake of Aurantii Immatri Pericarpium containing nobiletin and tangeretin as active compounds might be beneficial for preventing ischemic stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice.

PubMed

Jin, Ge; Bai, Dafeng; Yin, Shiliang; Yang, Zhihang; Zou, Dan; Zhang, Zhong; Li, Xiaoxiu; Sun, Yan; Zhu, Qiwen

2016-08-26

Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Aβ aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Suppression of hepatic stellate cell activation by microRNA-29b

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

Sekiya, Yumiko; Ogawa, Tomohiro; Liver Research Center, Graduate School of Medicine, Osaka City University, Osaka

Highlights: {yields} Expression of miR-29b was found to be down-regulated during the activation of hepatic stellate cells in primary culture. {yields} Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs. {yields} It blunted the increased expression of {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-b mRNAs essential for stellate cell activation. {yields} miR-29b overexpression led stellate cells to remain in a quiescent state, as evidenced by their star-like morphology. {yields} miR-29b overexpression suppressed the expression of c-fos mRNA. -- Abstract: MicroRNAs (miRNAs) participate in the regulation of cellular functions including proliferation, apoptosis, and migration. It has beenmore » previously shown that the miR-29 family is involved in regulating type I collagen expression by interacting with the 3'UTR of its mRNA. Here, we investigated the roles of miR-29b in the activation of mouse primary-cultured hepatic stellate cells (HSCs), a principal collagen-producing cell in the liver. Expression of miR-29b was found to be down-regulated during HSC activation in primary culture. Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs and additionally blunted the increased expression of {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-{beta}, which are key genes involved in the activation of HSCs. Further, overexpression of miR-29b led HSCs to remain in a quiescent state, as evidenced by their quiescent star-like cell morphology. Although phosphorylation of FAK, ERK, and Akt, and the mRNA expression of c-jun was unaffected, miR-29b overexpression suppressed the expression of c-fos mRNA. These results suggested that miR-29b is involved in the activation of HSCs and could be a candidate molecule for suppressing their activation and consequent liver fibrosis.« less

Attenuation of an original US porcine epidemic diarrhea virus strain PC22A via serial cell culture passage.

PubMed

Lin, Chun-Ming; Hou, Yixuan; Marthaler, Douglas G; Gao, Xiang; Liu, Xinsheng; Zheng, Lanlan; Saif, Linda J; Wang, Qiuhong

2017-03-01

Although porcine epidemic diarrhea (PED) has caused huge economic losses in the pork industry worldwide, an effective live, attenuated vaccine is lacking. In this study, an original US, highly virulent PED virus (PEDV) strain PC22A was serially passaged in Vero CCL81 and Vero BI cells. The virus growth kinetics in cell culture, virulence in neonatal pigs and the whole genomic sequences of selected passages were examined. Increased virus titers and sizes of syncytia were observed at the 65th passage level (P65) and P120, respectively. Based on the severity of clinical signs, histopathological lesions and the distribution of PEDV antigens in the gut, the virulence of P100 and above, but not P95C13 (CCL81), was markedly reduced in 4-day-old, caesarian-derived, colostrum-deprived piglets. Subsequently, the attenuation of P120 and P160 was confirmed in 4-day-old, conventional suckling piglets. Compared with P120, P160 replicated less efficiently in the intestine of pigs and induced a lower rate of protection after challenge. Sequence analysis revealed that the virulent viruses [P3 and P95C13 (CCL81)] had one, one, sixteen (including an early termination of nine amino acids) and two amino acid differences in non-structure protein 1 (nsp1), nsp4, spike and membrane proteins, respectively, from the fully attenuated P160. However, the overall pattern of attenuation-related genetic changes in PC22A differed from those of the other four pairs of PEDV wild type strains and their attenuated derivatives. These results suggest that PEDV attenuation can occur through multiple molecular mechanisms. The knowledge provides insights into potential molecular mechanisms of PEDV attenuation. Copyright © 2017 Elsevier B.V. All rights reserved.

Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

PubMed

Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2015-09-01

Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

PubMed Central

Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

2012-01-01

Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

Galantamine Attenuates Type 1 Diabetes and Inhibits Anti-Insulin Antibodies in Nonobese Diabetic Mice

PubMed Central

Hanes, William M; Olofsson, Peder S; Kwan, Kevin; Hudson, LaQueta K; Chavan, Sangeeta S; Pavlov, Valentin A; Tracey, Kevin J

2015-01-01

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic β-cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B-cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin (KLH) significantly suppressed splenocyte release of immunoglobulin G (IgG) and interleukin (IL)-4 and IL-6 during KLH challenge ex vivo. Administration of galantamine beginning at 1 month of age in nonobese diabetic (NOD) mice significantly delayed the onset of hyperglycemia, attenuated immune cell infiltration in pancreatic islets and decreased anti-insulin antibodies in serum. These observations indicate that galantamine attenuates experimental type 1 diabetes in mice and suggest that activation of the inflammatory reflex should be further studied as a potential therapeutic approach. PMID:26322849

27 CFR 28.144 - Export marks.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.144... § 28.144 Export marks. (a) General Requirement. In addition to the marks and brands required to be... brewer shall mark the word “Export” on each container or case of beer, or the words “Beer concentrate for...

27 CFR 28.103 - Export marks.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.103... Manufacturing Bonded Warehouse § 28.103 Export marks. (a) General. In addition to the marks and brands required... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

27 CFR 28.193 - Export marks.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

27 CFR 28.154 - Export marks.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.154..., for Exportation or Transfer to a Foreign-Trade Zone § 28.154 Export marks. In addition to the marks... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

Robotic assistance and general anaesthesia improve catheter stability and increase signal attenuation during atrial fibrillation ablation.

PubMed

Malcolme-Lawes, Louisa C; Lim, Phang Boon; Koa-Wing, Michael; Whinnett, Zachary I; Jamil-Copley, Shahnaz; Hayat, Sajad; Francis, Darrel P; Kojodjojo, Pipin; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa

2013-01-01

Recurrent arrhythmias after ablation procedures are often caused by recovery of ablated tissue. Robotic catheter manipulation systems increase catheter tip stability which improves energy delivery and could produce more transmural lesions. We tested this assertion using bipolar voltage attenuation as a marker of lesion quality comparing robotic and manual circumferential pulmonary vein ablation for atrial fibrillation (AF). Twenty patients were randomly assigned to robotic or manual AF ablation at standard radiofrequency (RF) settings for our institution (30 W 60 s manual, 25 W 30 s robotic, R30). A separate group of 10 consecutive patients underwent robotic ablation at increased RF duration, 25 W for 60 s (R60). Lesions were marked on an electroanatomic map before and after ablation to measure distance moved and change in bipolar electrogram amplitude during RF. A total of 1108 lesions were studied (761 robotic, 347 manual). A correlation was identified between voltage attenuation and catheter movement during RF (Spearman's rho -0.929, P < 0.001). The ablation catheter was more stable during robotic RF; 2.9 ± 2.3 mm (R30) and 2.6 ± 2.2 mm (R60), both significantly less than the manual group (4.3 ± 3.0 mm, P < 0.001). Despite improved stability, there was no difference in signal attenuation between the manual and R30 group. However, there was increased signal attenuation in the R60 group (52.4 ± 19.4%) compared with manual (47.7 ± 25.4%, P = 0.01). When procedures under general anaesthesia (GA) and conscious sedation were analysed separately, the improvement in signal attenuation in the R60 group was only significant in the procedures under GA. Robotically assisted ablation has the capability to deliver greater bipolar voltage attenuation compared with manual ablation with appropriate selection of RF parameters. General anaesthesia confers additional benefits of catheter stability and greater signal attenuation. These findings may have a significant impact on

1L Mark-IV Target Design Review

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

Koehler, Paul E.

This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

The research of laser marking control technology

NASA Astrophysics Data System (ADS)

Zhang, Qiue; Zhang, Rong

2009-08-01

In the area of Laser marking, the general control method is insert control card to computer's mother board, it can not support hot swap, it is difficult to assemble or it. Moreover, the one marking system must to equip one computer. In the system marking, the computer can not to do the other things except to transmit marking digital information. Otherwise it can affect marking precision. Based on traditional control methods existed some problems, introduced marking graphic editing and digital processing by the computer finish, high-speed digital signal processor (DSP) control marking the whole process. The laser marking controller is mainly contain DSP2812, digital memorizer, DAC (digital analog converting) transform unit circuit, USB interface control circuit, man-machine interface circuit, and other logic control circuit. Download the marking information which is processed by computer to U disk, DSP read the information by USB interface on time, then processing it, adopt the DSP inter timer control the marking time sequence, output the scanner control signal by D/A parts. Apply the technology can realize marking offline, thereby reduce the product cost, increase the product efficiency. The system have good effect in actual unit markings, the marking speed is more quickly than PCI control card to 20 percent. It has application value in practicality.

Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis

PubMed Central

Song, Zhenyuan; Deaciuc, Ion; Zhou, Zhanxiang; Song, Ming; Chen, Theresa; Hill, Daniell; McClain, Craig J.

2014-01-01

Although simple steatosis was originally thought to be a pathologically inert histological change, fat accumulation in the liver may play a critical role not only in disease initiation, but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Therefore, prevention of fat accumulation in the liver may be an effective therapy for multiple stages of nonalcoholic fatty liver disease (NAFLD). Promising beneficial effects of betaine supplementation on human NAFLD have been reported in some pilot clinical studies; however, data related to betaine therapy in NAFLD are limited. In this study, we examined the effects of betaine on fat accumulation in the liver induced by high-sucrose diet and evaluated mechanisms by which betaine could attenuate or prevent hepatic steatosis in this model. Male C57BL/6 mice weighing 20 ± 0.5 g (means ± SE) were divided into four groups (8 mice per group) and started on one of four treatments: standard diet (SD), SD+betaine, high-sucrose diet (HS), and HS + betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Long-term feeding of high-sucrose diet to mice caused significant hepatic steatosis accompanied by markedly increased lipogenic activity. Betaine significantly attenuated hepatic steatosis in this animal model, and this change was associated with increased activation of hepatic AMP-activated protein kinase (AMPK) and attenuated lipogenic capability (enzyme activities and gene expression) in the liver. Our findings are the first to suggest that betaine might serve as a therapeutic tool to attenuate hepatic steatosis by targeting the hepatic AMPK system. PMID:17702954

A novel approach to generating morbillivirus vaccines: negatively marking the rinderpest vaccine.

PubMed

Buczkowski, Hubert; Parida, Satya; Bailey, Dalan; Barrett, Thomas; Banyard, Ashley C

2012-03-02

The eradication of rinderpest virus (RPV) from the globe was possible through the availability of a safe and effective live attenuated vaccine and a suitable companion diagnostic test. However, the inability to serologically 'Differentiate between naturally Infected and Vaccinated Animals' (DIVA) meant that both the time taken to complete the eradication programme and the economic burden on countries involved was significantly greater than if a vaccine and companion diagnostic test that fulfilled the DIVA concept had been available. During the RPV eradication campaign serosurveillance for RPV was primarily based on a competitive ELISA using a RPV specific (C1) monoclonal antibody (mAb) directed against the viral haemagglutinin (H) protein but this test was not able to meet DIVA requirements. To provide proof of concept for the generation of novel morbillivirus DIVA vaccines we have identified, by phage display, and mutated residues critical for C1 mAb binding and assessed the functionality of mutants in an in vitro fusion assay. Finally we have incorporated mutated epitopes into a full length clone and rescued recombinant RPV using reverse genetics techniques. Here we describe a novel mechanism of marking morbillivirus vaccines, using RPV as a proof of concept, and discuss the applicability of this method to the development of marked vaccines for peste des petits ruminants virus (PPRV). Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

NASA Astrophysics Data System (ADS)

Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

2016-03-01

Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

Physical Activity Attenuates the Effect of Low Birth Weight on Insulin Resistance in Adolescents

PubMed Central

Ortega, Francisco B.; Ruiz, Jonatan R.; Hurtig-Wennlöf, Anita; Meirhaeghe, Aline; González-Gross, Marcela; Moreno, Luis A.; Molnar, Dénes; Kafatos, Anthony; Gottrand, Frederic; Widhalm, Kurt; Labayen, Idoia; Sjöström, Michael

2011-01-01

OBJECTIVE To examine whether physical activity influences the association between birth weight and insulin resistance in adolescents. RESEARCH DESIGN AND METHODS The study comprised adolescents who participated in two cross-sectional studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 520, mean age = 14.6 years) and the Swedish part of the European Youth Heart Study (EYHS) (n = 269, mean age = 15.6 years). Participants had valid data on birth weight (parental recall), BMI, sexual maturation, maternal education, breastfeeding, physical activity (accelerometry, counts/minute), fasting glucose, and insulin. Insulin resistance was assessed by homeostasis model assessment–insulin resistance (HOMA-IR). Maternal education level and breastfeeding duration were reported by the mothers. RESULTS There was a significant interaction of physical activity in the association between birth weight and HOMA-IR (logarithmically transformed) in both the HELENA study and the EYHS (P = 0.05 and P = 0.03, respectively), after adjusting for sex, age, sexual maturation, BMI, maternal education level, and breastfeeding duration. Stratified analyses by physical activity levels (below/above median) showed a borderline inverse association between birth weight and HOMA-IR in the low-active group (standardized β = −0.094, P = 0.09, and standardized β = −0.156, P = 0.06, for HELENA and EYHS, respectively), whereas no evidence of association was found in the high-active group (standardized β = −0.031, P = 0.62, and standardized β = 0.053, P = 0.55, for HELENA and EYHS, respectively). CONCLUSIONS Higher levels of physical activity may attenuate the adverse effects of low birth weight on insulin sensitivity in adolescents. More observational data, from larger and more powerful studies, are required to test these findings. PMID:21752955

iNKT-CELL ACTIVATION INDUCES LATE PRETERM BIRTH THAT IS ATTENUATED BY ROSIGLITAZONE1

PubMed Central

St Louis, Derek; Romero, Roberto; Plazyo, Olesya; Arenas-Hernandez, Marcia; Panaitescu, Bogdan; Xu, Yi; Milovic, Tatjana; Xu, Zhonghui; Bhatti, Gaurav; Qing-Sheng, Mi; Drewlo, Sascha; Tarca, Adi L.; Hassan, Sonia S.; Gomez-Lopez, Nardhy

2015-01-01

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality; however, its non-infection-related mechanisms are poorly understood. Herein, we show that the expansion of activated CD1d-restricted invariant NKT (iNKT) cells in the third trimester by administration of α-galactosylceramide (α-GalCer) induces late PTB and neonatal mortality. In vivo imaging revealed that fetuses from mice that underwent α-GalCer-induced late PTB had bradycardia and died shortly after delivery. Yet, administration of α-GalCer in the second trimester did not cause pregnancy loss. PPARγ activation, through rosiglitazone treatment, reduced the rate of α-GalCer-induced late PTB and improved neonatal survival. Administration of α-GalCer in the third trimester suppressed PPARγ activation as shown by the down-regulation of Fabp4 and Fatp4 in myometrial and decidual tissues, respectively; this suppression was rescued by rosiglitazone treatment. Administration of α-GalCer in the third trimester induced an increase in the activation of conventional CD4+ T cells in myometrial tissues and the infiltration of activated macrophages, neutrophils and mature DCs to myometrial and/or decidual tissues. All of these effects were blunted after rosiglitazone treatment. Administration of α-GalCer also up-regulated the expression of inflammatory genes at the maternal-fetal interface and systemically, and rosiglitazone treatment partially attenuated these responses. Finally, an increased infiltration of activated iNKT-like cells in human decidual tissues is associated with non-infection-related preterm labor/birth. Collectively, these results demonstrate that iNKT-cell activation in vivo leads to late PTB by initiating innate and adaptive immune responses and suggest that the PPARγ pathway has potential as a target for prevention of this syndrome. PMID:26740111

NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing inflammation response.

PubMed

Li, Yan; Liu, Chang; Wan, Xin-Shun; Li, Shao-Wei

2018-06-22

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1 -/- mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1 -/- significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1 -/- ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1 -/- /DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1 -/- . In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1 -/- /DR mice. Consistently, NLRP1 -/- attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1 -/- markedly decreased retina p-nuclear factor-κB (NF-κB), interleukin-1β (IL-1β) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRP1 inflammasome might be a promising strategy for DR therapy. Copyright © 2018. Published by Elsevier Inc.

Attenuated expression of interferon-β and interferon-λ1 by human alternatively activated macrophages.

PubMed

El Fiky, Ashraf; Perreault, Roger; McGinnis, Gwendolyn J; Rabin, Ronald L

2013-12-01

Macrophages can be polarized into classically (CAM) or alternatively (AAM) activated macrophages with IFN-γ or IL-4, respectively. CAM are associated with type 1 immune responses and are implicated in autoimmunity; AAM are associated with type 2 responses and are implicated in allergic diseases. An impediment in investigating macrophage biology using primary human monocyte derived macrophages is the wide inter-donor heterogeneity and the limited quantity of cells that survive in vitro polarization. To overcome this impediment, we established a protocol to generate CAM and AAM cultures derived from the THP-1 human promonocytic cell line. In this report, we demonstrate that THP-CAM and -AAM express gene and protein markers that define their primary human monocyte derived counterparts, such as IL-1β, CXCL10, and CXCL11 for CAM, and MRC1, IL-4 and CCL22 for AAM. In addition, we demonstrate that STAT6 is selectively activated in THP-AAM which, upon LPS stimulation, have an attenuated or delayed expression of IFN-β, IFN-λ1, and IFN α/β pathway genes compared to their CAM counterparts. Taken together, these findings may help further investigate human diseases associated with the alternatively activated macrophage phenotype using this reproducible in vitro macrophage model. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Dapper1 attenuates hepatic gluconeogenesis and lipogenesis by activating PI3K/Akt signaling.

PubMed

Kuang, Jian-Ren; Zhang, Zhi-Hui; Leng, Wei-Ling; Lei, Xiao-Tian; Liang, Zi-Wen

2017-05-15

Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca 2+ -mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver. It also increased Akt (pAkt) signaling and repressed both gluconeogenesis and lipogenesis. Conversely, Ad-shDapper1-induced knockdown of hepatic Dapper1 promoted gluconeogenesis and lipogenesis. Furthermore, Dapper1 activated PI3K p110α/Akt in an insulin-independent manner by inducing ATP production and secretion in vitro. Blockade of P2 ATP receptors, the downstream phospholipase C (PLC), or the inositol triphosphate receptor (IP3R all reduced the Dapper1-induced increase in cytosolic free calcium and Dapper1-mediated PI3K/Akt activation, as did removal of calcium in the medium. In conclusion, Dapper1 attenuates hepatic gluconeogenesis and lipogenesis in T2D. Copyright © 2017 Elsevier B.V. All rights reserved.

Meetings with Mark Vishik

NASA Astrophysics Data System (ADS)

Kalikinskaya, E. I.

2014-12-01

Mark Iosifovich Vishik was my husband Vladimir Chepyzhov's advisor during his years as a student in the Faculty of Mechanics and Mathematics at Moscow State University, and afterwards they worked together for almost 30 years. This is why I knew him personally while not being a mathematician myself: we sometimes talked on the phone, and met during common trips and a few holidays. In his last years, after the death of his devoted wife who was also his best friend, my husband and I decided to visit Mark regularly in order to comfort him in his loneliness, and many other of his friends did the same. I can say without exaggeration that Mark loved to talk with me about everyday matters, to reminisce about his wife Asya Moiseevna, their friends and relatives, to tell stories of his youth and the wonderful encounters that had so enriched his life. We had the idea to write down our conversations and publish them as a book. Unfortunately, few such conversations lay ahead. The last one took place in January 2010. We did not write a book, but we did write an article [1], which was published in English in the form of an interview with Mark. The present article is based on our conversations with Mark. Here I will try to recount his memories about people who played an important role in his life.

Plasma Parameters From Reentry Signal Attenuation

DOE PAGES

Statom, T. K.

2018-02-27

This study presents the application of a theoretically developed method that provides plasma parameter solution space information from measured RF attenuation that occurs during reentry. The purpose is to provide reentry plasma parameter information from the communication signal attenuation. The theoretical development centers around the attenuation and the complex index of refraction. The methodology uses an imaginary index of the refraction matching algorithm with a tolerance to find suitable solutions that satisfy the theory. The imaginary matching terms are then used to determine the real index of refraction resulting in the complex index of refraction. Then a filter is usedmore » to reject nonphysical solutions. Signal attenuation-based plasma parameter properties investigated include the complex index of refraction, plasma frequency, electron density, collision frequency, propagation constant, attenuation constant, phase constant, complex plasma conductivity, and electron mobility. RF plasma thickness attenuation is investigated and compared to the literature. Finally, similar plasma thickness for a specific signal attenuation can have different plasma properties.« less

Plasma Parameters From Reentry Signal Attenuation

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

Statom, T. K.

This study presents the application of a theoretically developed method that provides plasma parameter solution space information from measured RF attenuation that occurs during reentry. The purpose is to provide reentry plasma parameter information from the communication signal attenuation. The theoretical development centers around the attenuation and the complex index of refraction. The methodology uses an imaginary index of the refraction matching algorithm with a tolerance to find suitable solutions that satisfy the theory. The imaginary matching terms are then used to determine the real index of refraction resulting in the complex index of refraction. Then a filter is usedmore » to reject nonphysical solutions. Signal attenuation-based plasma parameter properties investigated include the complex index of refraction, plasma frequency, electron density, collision frequency, propagation constant, attenuation constant, phase constant, complex plasma conductivity, and electron mobility. RF plasma thickness attenuation is investigated and compared to the literature. Finally, similar plasma thickness for a specific signal attenuation can have different plasma properties.« less

Effects of Mental Fatigue on Physical Endurance Performance and Muscle Activation Are Attenuated by Monetary Incentives.

PubMed

Brown, Denver M Y; Bray, Steven R

2017-12-01

Physical performance is impaired following cognitive control exertion. Incentives can ameliorate adverse carryover effects of cognitive control exertion but have not been investigated for physical endurance. This study examined the effect of monetary incentives on physical performance and muscle activation following exposure to a mentally fatiguing, cognitive control task. Participants (N = 82) performed two isometric endurance handgrip trials separated by a 12-min cognitive control manipulation using a 2 (high cognitive control [HCC]/low cognitive control [LCC]) × 2 (incentive/no incentive) design. Mental fatigue was significantly higher in the HCC conditions. Performance decreased in the HCC/no incentive condition but was unaffected in the HCC/incentive condition, which did not differ from the low cognitive control conditions. Electromyography data revealed increased muscle activation in the HCC/no incentive condition, which was also attenuated in the HCC/incentive condition. Findings show that incentives counteract the negative effects of HCC on physical endurance and alter central drive to motor units.

Landing gear noise attenuation

NASA Technical Reports Server (NTRS)

Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Abeysinghe, Amal (Inventor); Kwan, Hwa-Wan (Inventor)

2011-01-01

A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

Swash mark and grain flow

USGS Publications Warehouse

Sallenger,, Asbury H.

1981-01-01

Swash marks composed entirely of coarse sand are commonly found on coarse-sand beaches. These swash marks are 10 to 30 centimeters in width and a few millimeters to one centimeter in height. Previous observations, mostly on finer-sand beaches, indicate swash marks are seldom over a few millimeters in height and are commonly composed of material readily floated by surface tension (e.g., mica flakes and shell fragments). Swash marks composed of coarse sand have both fining seaward and fining with depth trends in grain size. Apparently, the leading margin of a wave upwash drives a highly concentrated flow of grains in which both grain size and grain velocity decrease with depth. Therefore, large grains are transported at greater velocities than are smaller grains. Thus, at the maximum advance of an upwash, a swash mark is deposited which has the observed fining seaward and fining with depth trends in grain size.

Seismic Attenuation in the African LLSVP Estimated from PcS Phases

NASA Astrophysics Data System (ADS)

Liu, C.; Grand, S.

2017-12-01

Seismic tomography has shown that the lowermost mantle beneath the south central Pacific and southern Africa are marked by broad regions with 3% slower shear velocity than normal. The structures have come to be known as large-low-shear-velocity provinces (LLSVPs). The cause of the seismic anomalies associated with the LLSVPs is of great interest to geophysicists as they are related to the chemical, thermal, and dynamic structure of the mantle. Some have interpreted the heterogeneity in the LLSVPs to be caused by purely thermal effects while others believe the LLSVPs are chemically distinct from normal mantle. Seismic velocity variations alone cannot distinguish the thermal from chemical interpretations. Anelastic structure, however, can help discriminate among models of the LLSVPs as intrinsic attenuation is much more sensitive to temperature than to chemical variations. In this study, we use PcS seismic waves, from an earthquake located in the Scotia Arc, recorded by 50 broadband seismometers deployed in Southern Africa during the Kaapvaal experiment (1997-1999) to estimate Q in the African LLSVP. With increasing epicentral distances, the upward leg PcS waves in lower mantle sweep from normal mantle into the African LLSVP. We divided the PcS data into a group that sampled the LLSVP and another group that passed through normal lower mantle. We determined Δt* between these two groups by stacking spectra and using the spectral ratio method. The waves passing through the LLSVP are noticeably more attenuated than those outside. Taking Q values outside the LLSVP from different published 1D Q models (e.g. PREM [Dziewonski and Anderson, 1981]; QLM9 [Lawrence and Wysession, 2006a]; QHR12 [Hwang and Ritsema, 2011]), we estimate the corresponding average shear wave Q in the African LLSVP to be 127, 115, and 118, far lower than any published average Earth Q models for the lower mantle. Using a range of activation energies (E*), from 200 - 500 kJ/mol (Matas and Bukowinski

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

PubMed

Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

2010-04-16

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone

Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice.

PubMed

Chen, Xiahong; Gong, Xia; Jiang, Rong; Wang, Bin; Kuang, Ge; Li, Ke; Wan, Jingyuan

2016-01-01

Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl4)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl4-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl4-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl4-induced liver injury. These results suggest that RvD1 could effectively prevent CCl4-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1.

Transcription factors, coregulators, and epigenetic marks are linearly correlated and highly redundant

PubMed Central

Ahsendorf, Tobias; Müller, Franz-Josef; Topkar, Ved; Gunawardena, Jeremy; Eils, Roland

2017-01-01

The DNA microstates that regulate transcription include sequence-specific transcription factors (TFs), coregulatory complexes, nucleosomes, histone modifications, DNA methylation, and parts of the three-dimensional architecture of genomes, which could create an enormous combinatorial complexity across the genome. However, many proteins and epigenetic marks are known to colocalize, suggesting that the information content encoded in these marks can be compressed. It has so far proved difficult to understand this compression in a systematic and quantitative manner. Here, we show that simple linear models can reliably predict the data generated by the ENCODE and Roadmap Epigenomics consortia. Further, we demonstrate that a small number of marks can predict all other marks with high average correlation across the genome, systematically revealing the substantial information compression that is present in different cell lines. We find that the linear models for activating marks are typically cell line-independent, while those for silencing marks are predominantly cell line-specific. Of particular note, a nuclear receptor corepressor, transducin beta-like 1 X-linked receptor 1 (TBLR1), was highly predictive of other marks in two hematopoietic cell lines. The methodology presented here shows how the potentially vast complexity of TFs, coregulators, and epigenetic marks at eukaryotic genes is highly redundant and that the information present can be compressed onto a much smaller subset of marks. These findings could be used to efficiently characterize cell lines and tissues based on a small number of diagnostic marks and suggest how the DNA microstates, which regulate the expression of individual genes, can be specified. PMID:29216191

48 CFR 227.7103-10 - Contractor identification and marking of technical data to be furnished with restrictive markings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and marking of technical data to be furnished with restrictive markings. 227.7103-10 Section 227.7103... DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Technical Data 227.7103-10 Contractor identification and marking of technical data to be furnished with restrictive markings...

Geldanamycin attenuates 3-nitropropionic acid-induced apoptosis and JNK activation through the expression of HSP 70 in striatal cells

PubMed Central

CHOI, YONG-JOON; KIM, NAM HO; LIM, MAN SUP; LEE, HEE JAE; KIM, SUNG SOO; CHUN, WANJOO

2014-01-01

Although selective striatal cell death is a characteristic hallmark in the pathogenesis of Huntington’s disease (HD), the underlying mechanism of striatal susceptibility remains to be clarified. Heat shock proteins (HSPs) have been reported to suppress the aggregate formation of mutant huntingtin and concurrent striatal cell death. In a previous study, we observed that heat shock transcription factor 1 (HSF1), a major transcription factor of HSPs, significantly attenuated 3-nitropropionic acid (3NP)-induced reactive oxygen species (ROS) production and apoptosis through the expression of HSP 70 in striatal cells. To investigate the differential roles of HSPs in 3NP-induced striatal cell death, the effect of geldanamycin (GA), an HSP 90 inhibitor, was examined in 3NP-stimulated striatal cells. GA significantly attenuated 3NP-induced striatal apoptosis and ROS production with an increased expression of HSP 70. Triptolide (TL), an HSP 70 inhibitor, abolished GA-mediated protective effects in 3NP-stimulated striatal cells. To understand the underlying mechanism by which GA-mediated HSP 70 protects striatal cells against 3NP stimulation, the involvement of various signaling pathways was examined. GA significantly attenuated 3NP-induced c-Jun N-terminal kinase (JNK) phosphorylation and subsequent c-Jun phosphorylation in striatal cells. Taken together, the present study demonstrated that GA exhibits protective properties against 3NP-induced apoptosis and JNK activation via the induction of HSP 70 in striatal cells, suggesting that expression of HSP 70 may be a valuable therapeutic target in the treatment of HD. PMID:24756698

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

PubMed

Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

2016-07-01

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Attenuation in gas-charged magma

NASA Astrophysics Data System (ADS)

Collier, L.; Neuberg, J. W.; Lensky, N.; Lyakhovsky, V.; Navon, O.

2006-05-01

Low frequency seismic events observed on volcanoes, such as Soufriere Hills Volcano, Montserrat, are thought to be caused by a resonating system. The modelling of seismic waves in gas-charged magma is critical for the understanding of seismic resonance effects in conduits, dykes and cracks. Seismic attenuation, which depends mainly on magma viscosity, gas and crystal content, is an essential factor in such modelling attempts. So far only two-phase gas-melt systems with the assumption of no diffusion and transport of volatiles between the melt and the gas bubbles have been considered. In this study, we develop a method of quantifying attenuation within gas-charged magma, including the effects of diffusion and exsolution of gas into the bubbles. The results show that by including such bubble growth processes attenuation levels are increased within magma. The resulting complex behaviour of attenuation with pressure and frequency indicates that two factors are controlling attenuation, the first due to viscous hindrance or the melt, and the second due diffusion processes. The level of attenuation within a gas-charged magma conduit suggests an upper limit on the length of a resonating conduit section of just a few hundred meters.

Restoration of Akt activity by the bisperoxovanadium compound bpV(pic) attenuates hippocampal apoptosis in experimental neonatal pneumococcal meningitis

PubMed Central

Sury, Matthias D; Vorlet-Fawer, Lorianne; Agarinis, Claudia; Yousefi, Shida; Grandgirard, Denis; Leib, Stephen L; Christen, Stephan

2010-01-01

Pneumococcal meningitis causes apoptosis of developing neurons in the dentate gyrus of the hippocampus. The death of these cells is accompanied with long-term learning and memory deficits in meningitis survivors. Here, we studied the role of the PI3K/Akt (protein kinase B) survival pathway in hippocampal apoptosis in a well-characterized infant rat model of pneumococcal meningitis. Meningitis was accompanied by a significant decrease of the PI3K product phosphatidylinositol 3,4,5-triphosphate (PIP3) and of phosphorylated (i.e., activated) Akt in the hippocampus. At the cellular level, phosphorylated Akt was decreased in both the granular layer and the subgranular zone of the dentate gyrus, the region where the developing neurons undergo apoptosis. Protein levels and activity of PTEN, the major antagonist of PI3K, were unaltered by infection, suggesting that the observed decrease in PIP3 and Akt phosphorylation is a result of decreased PI3K signaling. Treatment with the PTEN inhibitor bpV(pic) restored Akt activity and significantly attenuated hippocampal apoptosis. Co-treatment with the specific PI3K inhibitor LY294002 reversed restoration of Akt activity and attenuation of hippocampal apoptosis, while it had no significant effect on these parameters on its own. These results indicate that the inhibitory effect of bpV(pic) on apoptosis was mediated by PI3K-dependent activation of Akt, strongly suggesting that bpV(pic) acted on PTEN. Treatment with bpV(pic) also partially inhibited the concentration of bacteria and cytokines in the CSF, but this effect was not reversed by LY294002, indicating that the effect of bpV(pic) on apoptosis was independent of its effect on CSF bacterial burden and cytokine levels. These results indicate that the PI3K/Akt pathway plays an important role in the death and survival of developing hippocampal neurons during the acute phase of pneumococcal meningitis. PMID:20875857

Wet night visibility of pavement markings.

DOT National Transportation Integrated Search

2004-01-01

This report describes an investigation into the performance of pavement markings in wet night conditions. The performance of a typical pavement marking will degrade when it gets wet. This is a result of the flooding of the marking optics, thereby red...

9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

Code of Federal Regulations, 2011 CFR

2011-01-01

... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

Code of Federal Regulations, 2013 CFR

2013-01-01

... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

Code of Federal Regulations, 2014 CFR

2014-01-01

... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

Code of Federal Regulations, 2010 CFR

2010-01-01

... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

9 CFR 317.3 - Approval of abbreviations of marks of inspection; preparation of marking devices bearing...

Code of Federal Regulations, 2012 CFR

2012-01-01

... marking device containing any official mark or simulation thereof, or any label bearing any such mark or simulation, without the written authority therefor of the Administrator. However, when any such sample label... inspection legend, or simulation thereof, shown in § 312.2(a), § 312.3(a) (only the legend appropriate for...

Eriodictyol Attenuates Myocardial Ischemia-Reperfusion Injury through the Activation of JAK2

PubMed Central

Li, Defang; Lu, Ning; Han, Jichun; Chen, Xiaoyu; Hao, Wenjin; Xu, Wenjuan; Liu, Xiaona; Ye, Lei; Zheng, Qiusheng

2018-01-01

Myocardial ischemia-reperfusion (I/R) injury remains the leading risk factor of disability and mortality worldwide. In this study, the myocardial protective effect of eriodictyol (EDT) and the underlying mechanism in an ex vivo model of global myocardial I/R was investigated. After treatment with different concentrations of EDT, the decreased hemodynamic parameters induced by myocardial I/R injury were significantly attenuated by EDT. The elevated levels of IL-6, CRP, IL-8, and TNF-α were effectively reduced by EDT treatment. EDT also remarkably suppressed the levels of Bax and cleaved Caspase-3, and up-regulated the level of Bcl-2 in cardiac tissues from EDT-treated groups. Further studies showed that EDT could increase the levels of p-JAK2 and p-STAT3 in cardiac tissues. Meanwhile, treatment of AG490, a specific inhibitor of JAK2, abolished the protective effect of EDT on hemodynamic parameters, myocardial inflammation and myocardial cell apoptosis induced by I/R injury. These results demonstrated that EDT could protect against myocardial I/R injury through the activation of JAK2, providing a potential treatment with EDT during myocardial I/R injury. PMID:29441020

Effects of Uncertainty in TRMM Precipitation Radar Path Integrated Attenuation on Interannual Variations of Tropical Oceanic Rainfall

NASA Technical Reports Server (NTRS)

Robertson, Franklin R.; Fitzjarrald, Dan E.; Kummerow, Christian D.; Arnold, James E. (Technical Monitor)

2002-01-01

Considerable uncertainty surrounds the issue of whether precipitation over the tropical oceans (30 deg N/S) systematically changes with interannual sea-surface temperature (SST) anomalies that accompany El Nino (warm) and La Nina (cold) events. Time series of rainfall estimates from the Tropical Rainfall Measuring Mission (TRMM Precipitation Radar (PR) over the tropical oceans show marked differences with estimates from two TRMM Microwave Imager (TMI) passive microwave algorithms. We show that path-integrated attenuation derived from the effects of precipitation on the radar return from the ocean surface exhibits interannual variability that agrees closely with the TMI time series. Further analysis of the frequency distribution of PR (2A25 product) rain rates suggests that the algorithm incorporates the attenuation measurement in a very conservative fashion so as to optimize the instantaneous rain rates. Such an optimization appears to come at the expense of monitoring interannual climate variability.

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

PubMed

Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

2017-07-10

The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats.

PubMed

Lu, Lijuan; Pan, Cailong; Chen, Lu; Hu, Liang; Wang, Chaoyu; Han, Yuan; Yang, Yanjing; Cheng, Zhixiang; Liu, Wen-Tao

2017-04-01

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

A novel synthetic phosphodiesterase 5 inhibitor, KJH-1002, ameliorates scopolamine-induced cognitive impairments in mice by activating the cGMP/CREB signaling pathway and attenuating oxidative damage.

PubMed

Zhang, Lijun; Seo, Jae Hong; Li, Huan; Nam, Ghilsoo; Yang, Hyun Ok

2018-05-30

Inhibition of PDE5 has been demonstrated to improve synaptic plasticity and memory via enhancing of cGMP expression, thus activating the cGMP/CREB signaling pathway. This study aimed to investigate the ameliorating effect of PDE5 inhibitor on scopolamine-induced cognitive dysfunction using memory-related behavioral tests and biochemical assays. After the mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine administration. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using western blot and spectrophotometry, respectively. KJH-1002, a novel inhibitor of phosphodiesterase 5 (PDE5), was synthesized (IC 50 of 0.059 ±0.04 nmol·L -1 ), and it markedly improved the memory performance impaired by scopolamine in the behavioral tests, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased the cGMP level in the cortex, the scopolamine-reduced expression of phosphorylated cAMP response element binding protein (CREB), extracellular-regulated kinase 1/2 (ERK 1/2), protein kinase B (Akt) and brain-derived neurotrophic factor (BDNF) in the cortex and hippocampus were reversed by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), and decreased the level of malondialdehyde (MDA). KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signaling pathway and attenuating oxidative stress. The beneficial effect of KJH-1002 on cognition suggests its potential as a therapeutic candidate for Alzheimer's disease. This article is protected by copyright. All rights reserved.

Adrenergic blocker carvedilol attenuates the cardiovascular and aversive effects of nicotine in abstinent smokers.

PubMed

Sofuoglu, Mehmet; Mouratidis, Maria; Yoo, Sonah; Kosten, Thomas

2006-12-01

The cardiovascular response to nicotine is mediated mainly by noradrenergic activation. Whether noradrenergic activation mediates other effects of nicotine has not been well documented in humans. In this study, we examined the effects of an alpha and beta-adrenergic receptor blocker: carvedilol, on cardiovascular and subjective responses to nicotine lozenge and on the ability of nicotine lozenge to suppress tobacco withdrawal symptoms in overnight abstinent smokers. Fifteen smokers, nine men and six women, participated in a double-blind, placebo-controlled, crossover study. In each of the three experimental sessions, participants were treated orally with a single 25 or 50 mg dose of carvedilol or placebo. Two hours and 10 min following the medication treatment, participants received a single 4 mg nicotine lozenge. Carvedilol treatment attenuated the nicotine-induced heart rate, systolic and diastolic blood pressure increases. Carvedilol also attenuated the self-report rating of 'bad effects' in response to nicotine. Carvedilol, alone or in combination with nicotine lozenge, did not affect tobacco withdrawal symptoms. Carvedilol treatment did not affect performance on the Stroop Test. These results support the effectiveness of carvedilol for attenuating the cardiovascular effects of nicotine. Attenuation of the rating of 'bad effects' by carvedilol suggests that noradrenergic activation may also mediate the aversive effects of nicotine.

Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin.

PubMed

Choi, Cheol Hee; Jang, Chul Ho; Cho, Yong Bum; Jo, Si Young; Kim, Min Young; Park, Byung Young

2012-04-01

Oxytetracycline and ilomastat are inhibitors of matrix metalloproteinases (MMPs). Their efficacy in protecting against cochlear damage induced by the intratympanic instillation of lipopolysaccharide (LPS), as a means of inducing labyrinthitis, was investigated. Experiments were performed in 21 young male guinea pigs. Intratympanic instillation of LPS was done in the control group (n=7). Intratympanic instillation of oxytetracycline or ilomastat was done after LPS instillation in the experimental group. Measurements of auditory brainstem response (ABR) and cochlear blood flow (CBF) were performed. The organ of Corti was evaluated by field emission scanning electron microscopy (FE-SEM). The blood-labyrinth barrier (BLB) integrity was evaluated with Evans blue uptake. Gelatin zymography was used to assess the expression of active MMP-2 and MMP-9. Ears treated with MMP inhibitors were significantly protected from hearing loss compared to the LPS group. In LPS group, there was a significant decrease of CBF. However, experimental group displayed a statistically significant recovery of CBF. FE-SEM revealed hair cell damage in the LPS-treated group, but hair cells presented a normal appearance in MMP inhibitors. The LPS group showed a marked increase of Evans blue extravasation in the cochlea. However, MMP inhibitors significantly reduced the BLB opening. Active MMP-9 was expressed in the LPS group. Treatment with MMP inhibitors attenuated active MMP-9 expression. The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

PubMed Central

Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

2014-01-01

Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

Attenuation of aortic aneurysms with stem cells from different genders.

PubMed

Davis, John P; Salmon, Morgan; Pope, Nicolas H; Lu, Guanyi; Su, Gang; Sharma, Ashish K; Ailawadi, Gorav; Upchurch, Gilbert R

2015-11-01

No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Adjustable Optical-Fiber Attenuator

NASA Technical Reports Server (NTRS)

Buzzetti, Mike F.

1994-01-01

Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

Dropping sand bags from helicopters: A low cost and environmentally benign approach to determine subsurface velocity and attenuation structure of active volcanic systems

NASA Astrophysics Data System (ADS)

Jolly, A. D.; Chardot, L.; Sherburn, S.; Cole-Baker, J.; Scott, B. J.; Fournier, N.; Neuberg, J. N.

2012-04-01

Obtaining estimates of the seismic velocity and attenuation structure of volcanic systems is considered valuable from a monitoring perspective but can be extremely costly and time consuming due to the potential environmental impacts, safety issues and the permitting process. Here, we present an easy, low cost and environmentally benign alternative whereby the shallow velocity and attenuation structure can be obtained via high impact sandbag drops from helicopter. We conducted such a sandbag drop experiment at White Island volcano on 23 September 2011, during the final stage of a 6 month deployment of 14 broadband seismometers. Three drops were attempted, two at either end of a 5 station linear array within the crater floor, and the third within the volcano's shallow active acid crater lake. The bags were dropped from ~400 m height and contained ~700 kg of fine beach sand held within nylon sacks having a volume capacity of ~2.0 m3. The impact velocity was estimated at ~70 m/s yielding a kinetic energy of about 106 to 107 Nm. The source position was established by GPS on the resulting impact crater and was accurate to within ~5 m. The lake drop position was estimated from video footage relative to known ground features and was accurate to ~30 m. Impact timing was achieved by drop placement close to, but not on, the nearby seismometer recording systems. For the crater floor drops the timing was constrained to within ~0.05 s based on distance from the closest stations. The low kinetic energy and strong attenuation of the crater floor meant that strong first-P arrival times were limited to an area within ~1 km of the impact position. We obtained a rough velocity estimate of about 1.0-1.5 km/s for the unconsolidated crater floor and a velocity of ~1.5-2.0 km/s for rays traversing mostly through the consolidated rocks comprising the crater walls. Attenuation was found to be generally very strong (Q < 10) for both consolidated and unconsolidated parts of the volcano

NATURAL ATTENUATION FOR ECOSYSTEM RESTORATION IN NY/NJ HARBOR

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

Van der Lelie, D.; Reid-Green, J. D.; Stern, E. A.

2003-12-31

We have investigated the feasibility of using natural attenuation methods for ecosystem restoration in New York/New Jersey Harbor. Measurements were made of the most probable number of sulfate-reducing bacteria (SRB) in native sediments and in samples, which had been supplemented with an appropriate electron donor and electron acceptor. The results showed that the activity of the endogenous microbial population in the native sediment was high enough to make possible adequate chemical transformation rates. The bioavailability of the zinc in the sediments was measured using the BIOMET biosensor technique. The bioavailability of the zinc was effectively eliminated following the microbial activities.more » We concluded that natural attenuation could be used effectively in treating sediments from Newark Bay and surrounding waters and that the resultant materials could likely be used in environmental restoration projects of the type proposed for construction in South Kearny, NJ.« less

Global Attenuation Tomography and Implications for Upper-Mantle Thermal Structure

NASA Astrophysics Data System (ADS)

Dalton, C. A.; Ekström, G.; Dziewonski, A. M.

2007-12-01

tectonically active continental areas are associated with slower velocities and higher attenuation than stable continental interiors. At depths of 150 and 200 km, oceanic regions exhibit a larger decrease in attenuation per fractional increase in velocity than stable continental regions do, suggesting differences in the mechanisms that influence the seismic properties within these two regions. Comparison with recent laboratory measurements (Faul and Jackson, 2005) of attenuation and velocity for olivine helps to quantify the extent to which temperature alone can explain the observed variability. We find that the mineral-physics predictions agree well with the global seismic models for the oceanic regions between 150- and 250-km depth, but that the cratonic areas cannot be fit.

49 CFR 15.13 - Marking SSI.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.13 Marking... document. (b) Protective marking. The protective marking is: SENSITIVE SECURITY INFORMATION. (c... Sensitive Security Information that is controlled under 49 CFR parts 15 and 1520. No part of this record may...

49 CFR 15.13 - Marking SSI.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Office of the Secretary of Transportation PROTECTION OF SENSITIVE SECURITY INFORMATION § 15.13 Marking... document. (b) Protective marking. The protective marking is: SENSITIVE SECURITY INFORMATION. (c... Sensitive Security Information that is controlled under 49 CFR parts 15 and 1520. No part of this record may...

46 CFR 160.060-8 - Marking.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

46 CFR 160.060-8 - Marking.

Code of Federal Regulations, 2012 CFR

2012-10-01

...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

46 CFR 160.060-8 - Marking.

Code of Federal Regulations, 2013 CFR

2013-10-01

...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160.060-8 Marking. (a) Each buoyant vest must have the following information clearly... manufacturer or distributor). (Lot No.). (b) Waterproof marking. Marking of buoyant vests shall be sufficiently...

Blocking oxytocin receptors inhibits vaginal marking to male odors in female Syrian hamsters.

PubMed

Martinez, Luis A; Albers, H Elliott; Petrulis, Aras

2010-12-02

In Syrian hamsters (Mesocricetus auratus), precopulatory behaviors such as vaginal scent marking are essential for attracting a suitable mate. Vaginal marking is dependent on forebrain areas implicated in the neural regulation of reproductive behaviors in rodents, including the medial preoptic/anterior hypothalamus (MPOA-AH). Within MPOA-AH, the neuropeptide oxytocin (OT) acts to facilitate copulation (lordosis), as well as ultrasonic vocalizations towards males. It is not known, however, if OT in this area also facilitates vaginal marking. In the present study, a specific oxytocin receptor antagonist (OTA) was injected into MPOA-AH of intact female Syrian hamsters to determine if oxytocin receptor-dependent signaling is critical for the normal expression of vaginal marking elicited by male, female, and clean odors. OTA injections significantly inhibited vaginal marking in response to male odors compared with vehicle injections. There was no effect of OTA on marking in response to either female or clean odors. When injected into the bed nucleus of the stria terminalis (BNST), a nearby region to MPOA-AH, OTA was equally effective in decreasing marking. Finally, the effects of OTA appear to be specific to vaginal marking, as OTA injections in MPOA-AH or BNST did not alter general locomotor activity, flank marking, or social odor investigation. Considered together, these results suggest that OT in MPOA-AH and/or BNST normally facilitates male odor-induced vaginal marking, providing further evidence that OT generally supports prosocial interactions among conspecifics. Copyright © 2010 Elsevier Inc. All rights reserved.

Sulfated caffeic acid dehydropolymer attenuates elastase and cigarette smoke extract-induced emphysema in rats: sustained activity and a need of pulmonary delivery.

PubMed

Saluja, Bhawana; Li, Hua; Desai, Umesh R; Voelkel, Norbert F; Sakagami, Masahiro

2014-08-01

Although emphysema destroys alveolar structures progressively and causes death eventually, no drug has been discovered to prevent, intervene, and/or resolve this life-threatening disease. We recently reported that sulfated caffeic acid dehydropolymer CDSO3 is a novel potent triple-action inhibitor of elastolysis, oxidation, and inflammation in vitro, and therefore, a potential anti-emphysema agent. However, the in vivo therapeutic potency, duration and mode of actions, and effective route remain to be demonstrated. Emphysema was induced in rats with human sputum elastase (HSE) combined with cigarette smoke extract (CSE). CDSO3 at 5, 30, or 100 μg/kg was dosed to the lung or injected subcutaneously at 2, 6, or 24 h before or 1 or 24 h or 1 week after the HSE/CSE instillation. At 1 h or 48 h or on day 21-22 or day 28, lungs were examined for airway-to-blood injurious barrier damage; their elastolytic, oxidative, and inflammatory activities; lung luminal leukocytes infiltration; functional treadmill exercise endurance; and/or morphological airspace enlargement. CDSO3, when dosed to the lung at 30 or 100 μg/kg, but not via systemic subcutaneous injection, significantly (43-93 %) attenuated HSE/CSE-induced (1) barrier damage measured by luminal hemorrhage and protein leak; (2) elastolytic, oxidative, and inflammatory activities measured with elastase, reduced glutathione, and TNFα levels, respectively; (3) luminal neutrophil infiltration and tissue myeloperoxidase activity; (4) functional impairment of exercise endurance; and (5) airspace enlargement, in both preventive and interventional dosing protocols. Notably, the effects were shown to last for 24 h at the greater 100-μg/kg dose, and the 1-week-delayed administration was also capable of attenuating the development of emphysema. CDSO3 is a novel, potent, long-acting, nonpeptidic macromolecule that inhibits HSE/CSE-induced elastolysis, oxidation, and inflammation in the lung and thereby attenuates the development

Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice

PubMed Central

ZHAO, PENG; ZHOU, RU; ZHU, XIAO-YUN; HAO, YIN-JU; LI, NAN; WANG, JIE; NIU, YANG; SUN, TAO; LI, YU-XIANG; YU, JIAN-QIANG

2015-01-01

Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl-2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB

Joint estimation of activity and attenuation for PET using pragmatic MR-based prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG tracers

NASA Astrophysics Data System (ADS)

Ahn, Sangtae; Cheng, Lishui; Shanbhag, Dattesh D.; Qian, Hua; Kaushik, Sandeep S.; Jansen, Floris P.; Wiesinger, Florian

2018-02-01

Accurate and robust attenuation correction remains challenging in hybrid PET/MR particularly for torsos because it is difficult to segment bones, lungs and internal air in MR images. Additionally, MR suffers from susceptibility artifacts when a metallic implant is present. Recently, joint estimation (JE) of activity and attenuation based on PET data, also known as maximum likelihood reconstruction of activity and attenuation, has gained considerable interest because of (1) its promise to address the challenges in MR-based attenuation correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology, which is known to be the key to the success of JE. In this paper, we implement a JE algorithm using an MR-based prior and evaluate the algorithm using whole-body PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA PET/MR scanners with TOF capability. The weight of the MR-based prior is spatially modulated, based on MR signal strength, to control the balance between MRAC and JE. Large prior weights are used in strong MR signal regions such as soft tissue and fat (i.e. MR tissue classification with a high degree of certainty) and small weights are used in low MR signal regions (i.e. MR tissue classification with a low degree of certainty). The MR-based prior is pragmatic in the sense that it is convex and does not require training or population statistics while exploiting synergies between MRAC and JE. We demonstrate the JE algorithm has the potential to improve the robustness and accuracy of MRAC by recovering the attenuation of metallic implants, internal air and some bones and by better delineating lung boundaries, not only for FDG but also for more specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.

Evaluation of pavement marking performance.

DOT National Transportation Integrated Search

2008-06-01

The objective of the investigation was to evaluate the useful life of pavement markings. The Manual on Uniform Traffic Control Devices (MUTCD) provides general guidelines for the application and installation of pavement markings. However, performance...

49 CFR 180.515 - Markings.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Pressure converted tank cars must have the new specification and conversion date permanently marked in... the manway nozzle flange on the left side of the car. The marking may have the last numeral of the...

Marking Student Programs Using Graph Similarity

ERIC Educational Resources Information Center

Naude, Kevin A.; Greyling, Jean H.; Vogts, Dieter

2010-01-01

We present a novel approach to the automated marking of student programming assignments. Our technique quantifies the structural similarity between unmarked student submissions and marked solutions, and is the basis by which we assign marks. This is accomplished through an efficient novel graph similarity measure ("AssignSim"). Our experiments…

14 CFR 27.1555 - Control markings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

14 CFR 27.1555 - Control markings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

14 CFR 27.1555 - Control markings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

14 CFR 27.1555 - Control markings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control markings. 27.1555 Section 27.1555... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

14 CFR 27.1555 - Control markings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control markings. 27.1555 Section 27.1555... Control markings. (a) Each cockpit control, other than primary flight controls or control whose function... fuel controls— (1) Each fuel tank selector control must be marked to indicate the position...

Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

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

Tamminen, Jenni A.; Yin, Miao; Transplantation Laboratory, Haartman Institute, University of Helsinki

Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cellsmore » in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. - Highlights: • Activin-A and activin-B are highly expressed in mesothelioma. • Mesothelioma cell migration and invasive growth can be blocked with sActR2B. • Activin induced Smad3 activity is attenuated in invasive mesothelioma cells. • Activins induce ERK activity in mesothelioma cells.« less

Mark IVA microprocessor support

NASA Technical Reports Server (NTRS)

Burford, A. L.

1982-01-01

The requirements and plans for the maintenance support of microprocessor-based controllers in the Deep Space Network Mark IVA System are discussed. Additional new interfaces and 16-bit processors have introduced problems not present in the Mark III System. The need for continuous training of maintenance personnel to maintain a level of expertise consistent with the sophistication of the required tools is also emphasized.

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequentmore » challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.« less

Immobilized nickel hexacyanoferrate on activated carbons for efficient attenuation of radio toxic Cs(I) from aqueous solutions

NASA Astrophysics Data System (ADS)

Lalhmunsiama; Lalhriatpuia, C.; Tiwari, Diwakar; Lee, Seung-Mok

2014-12-01

The aim of this study is to immobilize nickel hexacyanoferrate onto the large surface of activated carbons (ACs) precursor to rice hulls and areca nut waste materials. These nickel hexacyanoferrate immobilized materials are then assessed in the effective attenuation of radio logically important cesium ions from aqueous solutions. The solid samples are characterized by the XRD analytical method and surface morphology is obtained from the SEM images. The batch reactor experiments show that an increase in sorptive pH (2.0-10.0) apparently not affecting the high percent uptake of Cs(I). Equilibrium modeling studies suggest that the data are reasonably and relatively fitted well to the Langmuir adsorption isotherm. Kinetic studies show that sorption process is fairly rapid and the kinetic data are fitted well to the pseudo-second order rate model. Increasing the background electrolyte concentration from 0.001 to 0.1 mol/L NaCl causes insignificant decrease in Cs(I) removal which infers the higher selectivity of these materials for Cs(I) from aqueous solutions. Further, the column reactor operations enable to obtain the breakthrough data which are then fitted to the Thomas non-linear equation as to obtain the loading capacity of column for Cs(I). The results show that the modified materials show potential applicability in the attenuation of radio toxic cesium from aqueous solution.

14 CFR 45.11 - Marking of products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...

14 CFR 45.11 - Marking of products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...

14 CFR 45.11 - Marking of products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.11 Marking of products. (a) Aircraft. A manufacturer of aircraft covered under § 21.182 of this chapter must mark each aircraft by attaching a...