Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology.

PubMed

Kodiha, Mohamed; Ho-Wo-Cheong, Dennis; Stochaj, Ursula

2011-12-01

5'-AMP-activated kinase (AMPK) regulates numerous biological events and is an essential target for the treatment of type 2 diabetes. The objectives of the present study were first to determine the compartment-specific effects of three established AMPK activators on Thr172 phosphorylation of the α-subunit, an indicator of AMPK activation. Second, we examined how cytoplasmic and nuclear processes are modulated by pharmacological AMPK activators. Specifically, the impact of phenformin, resveratrol, and 5-aminoimidazole-4-carboxamide riboside (AICAR) on Thr172 phosphorylation in the cytoplasm and nucleus was quantified by different methods. To analyze how these activators change cell physiology, we measured the inactivation of acetyl-CoA-carboxylase 1, a predominantly cytoplasmic enzyme that is crucial for lipid metabolism. As a criterion for activities associated with the nucleus, de novo RNA synthesis in nucleoli was quantified. Our studies demonstrate that pharmacological activators of AMPK can alter the balance between nuclear and cytoplasmic AMPK pools. Thus, phenformin and resveratrol caused a strong activation of AMPK in the cytoplasm, whereas the effect was less pronounced in nuclei. By contrast, AICAR elicited a comparable rise in Thr172 phosphorylation in both compartments. Notably, these activators differed drastically in their effects on physiological processes that are located in distinct subcellular compartments. All compounds led to a substantial inactivation of acetyl-CoA-carboxylase 1 in the cytoplasm, with only minor changes to the nuclear enzyme. In the nucleolus, transcription was strongly inhibited by resveratrol, while a moderate inhibition was observed with phenformin and AICAR. Taken together, the compartment-specific phosphorylation of AMPK and downstream events are determined by the activator.

The positional-specificity effect reveals a passive-trace contribution to visual short-term memory.

PubMed

Postle, Bradley R; Awh, Edward; Serences, John T; Sutterer, David W; D'Esposito, Mark

2013-01-01

The positional-specificity effect refers to enhanced performance in visual short-term memory (VSTM) when the recognition probe is presented at the same location as had been the sample, even though location is irrelevant to the match/nonmatch decision. We investigated the mechanisms underlying this effect with behavioral and fMRI studies of object change-detection performance. To test whether the positional-specificity effect is a direct consequence of active storage in VSTM, we varied memory load, reasoning that it should be observed for all objects presented in a sub-span array of items. The results, however, indicated that although robust with a memory load of 1, the positional-specificity effect was restricted to the second of two sequentially presented sample stimuli in a load-of-2 experiment. An additional behavioral experiment showed that this disruption wasn't due to the increased load per se, because actively processing a second object--in the absence of a storage requirement--also eliminated the effect. These behavioral findings suggest that, during tests of object memory, position-related information is not actively stored in VSTM, but may be retained in a passive tag that marks the most recent site of selection. The fMRI data were consistent with this interpretation, failing to find location-specific bias in sustained delay-period activity, but revealing an enhanced response to recognition probes that matched the location of that trial's sample stimulus.

Effects of hirudin-induced activation of nonenzymatic fibrinolysis during immobilization stress

NASA Technical Reports Server (NTRS)

Shapiro, F. B.; Baskova, I. P.; Cherkesova, L. U.; Lyapina, L. A.; Goldovskaya, M. D.

1980-01-01

The specific inhibitor of thrombin, hirudin, was used for studying the mechanism of the activating effect of ACTH and adrenalin on nonenzymatic fibrinolytic activity (NEFA), the latter characterizing the function of the anticoagulation system (ACS). Simultaneous administration of ACTH and hirudin to animals subjected to immobilization stress did not reduce the effect of ACTH on NEFA, while simultaneous administration of adrenalin and hirudin revealed a diminished effect of the former. This suggests different mechanisms of ACTH and adrenalin effects upon NEFA: the stimulating effect of norepinephrine is realized through throminogenesis followed by activation of the ACS function and by increased NEFA and therefore inhibitable by hirudin which forms an inactive complex with thrombin. In fact the stimulating effect of ACTH upon NEFA is brought about specifically by another route than thrombinogenesis and thus occurs in the presence of hirudin. Hirudin itself has no effect upon NEFA.

Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

PubMed Central

Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

2013-01-01

Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

Exoskeletons for industrial application and their potential effects on physical work load.

PubMed

de Looze, Michiel P; Bosch, Tim; Krause, Frank; Stadler, Konrad S; O'Sullivan, Leonard W

2016-05-01

The aim of this review was to provide an overview of assistive exoskeletons that have specifically been developed for industrial purposes and to assess the potential effect of these exoskeletons on reduction of physical loading on the body. The search resulted in 40 papers describing 26 different industrial exoskeletons, of which 19 were active (actuated) and 7 were passive (non-actuated). For 13 exoskeletons, the effect on physical loading has been evaluated, mainly in terms of muscle activity. All passive exoskeletons retrieved were aimed to support the low back. Ten-forty per cent reductions in back muscle activity during dynamic lifting and static holding have been reported. Both lower body, trunk and upper body regions could benefit from active exoskeletons. Muscle activity reductions up to 80% have been reported as an effect of active exoskeletons. Exoskeletons have the potential to considerably reduce the underlying factors associated with work-related musculoskeletal injury. Practitioner Summary: Worldwide, a significant interest in industrial exoskeletons does exist, but a lack of specific safety standards and several technical issues hinder mainstay practical use of exoskeletons in industry. Specific issues include discomfort (for passive and active exoskeletons), weight of device, alignment with human anatomy and kinematics, and detection of human intention to enable smooth movement (for active exoskeletons).

7 CFR 1485.15 - Activity plan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... participant shall develop a specific activity plan(s) based on its strategic plan and the allocation approval... any changes in strategy from the strategic plan; (iii) A budget for each proposed activity, identifying the source of funds; (iv) Specific goals and benchmarks to be used to measure the effectiveness of...

Inhibitory activity of analogs of AM-toxin, a host-specific phytotoxin from the Alternaria alternata apple pathotype, on photosynthetic O2 evolution in apple leaves.

PubMed

Miyashita, Masahiro; Nakamori, Tomoko; Miyagawa, Hisashi; Akamatsu, Miki; Ueno, Tamio

2003-03-01

The effect of the host-specific phytotoxins, AM-toxins, on the photosynthetic activity of leaves from susceptible apple cultivars was investigated by using an oxygen electrode. The photosynthetic O2 evolution was inhibited by AM-toxin I in a host-specific manner. The inhibitory activity of several AM-toxin analogs against photosynthesis was also evaluated and the findings were correlated with their necrosis-inducing activity.

Manipulating motor performance and memory through real-time fMRI neurofeedback.

PubMed

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-05-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback

PubMed Central

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-01-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

PubMed

Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R

2015-08-01

The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

PubMed

Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

2014-05-01

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

EPA Science Inventory

The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with pote...

The role of the microbiology laboratory in guiding formulary decisions.

PubMed

Stratton, C W

1988-08-01

Typically, P & T Committee antibiotic selection criteria have included such factors as cost, pharmacokinetics, side effects profile, spectrum of activity, and relative activity against specific pathogens. The microbiology laboratory can provide the P & T Committee with other useful information to help guide them in making even more appropriate and cost-effective formulary decisions. This information includes specific susceptibility data (including prevalence of pathogens, source of infection [community or nosocomial], anatomical site of isolates, specific unit or service where isolated, type of culture specimen, total number of pathogens in the hospital), resistance trends data, an evaluation of microbiologic data presented in published studies, further data regarding an antimicrobial's spectrum of activity and activity against specific pathogens, and the relevance and limitations of in vitro data. With this information in hand, P & T Committee should be in a much better position to optimize formulary decision-making.

New Perspectives on Specific Immune-Depletion Technique Using Monoclonal Antibodies against Small Active Molecules in Herbs

PubMed Central

Wang, Xue-Qian; Cheng, Fa-Feng; Qu, Hui-Hua; Zhao, Yan; Yu, Cai; Liu, Yuan-Jun; Zhu, Wen-Xiang; Wang, Qing-Guo

2014-01-01

One of the main focuses in Chinese Medicine research is the identification of efficacious components in Chinese herbal medicine (CHM). Studies in such area are difficult due to the complexity and the synergistic characteristics of CHM. Current methods to track and separate active components are not adequate to meet the needs of revealing effects and identify substances and pharmacological mechanisms, which directly restrict the modernization and globalization of CHM. In this paper, a new methodology to deplete a single active component via immunoassay was introduced. The specific active component in a CHM mixture can then be identified and studied through comparative analyses of the pharmacological effects before and after immune depletion. With this new methodology, degree of contribution of a particular component to the whole complex herbal mixture can be elucidated, and its synergistic property with other components can be determined. The new method can reflect not only the overall combined pharmacological effects of CHM but also the effect of individual component. It is an effective way to explain the degree of contribution of one specific component to the overall activity of a CHM prescription. PMID:24772180

Volatiles in Inter-Specific Bacterial Interactions

PubMed Central

Tyc, Olaf; Zweers, Hans; de Boer, Wietse; Garbeva, Paolina

2015-01-01

The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures of well-described bacterial genera. In this study we aimed to understand how inter-specific bacterial interactions affect the composition, production and activity of volatiles. Four phylogenetically different bacterial species namely: Chryseobacterium, Dyella, Janthinobacterium, and Tsukamurella were selected. Earlier results had shown that pairwise combinations of these bacteria induced antimicrobial activity in agar media whereas this was not the case for monocultures. In the current study, we examined if these observations were also reflected by the production of antimicrobial volatiles. Thus, the identity and antimicrobial activity of volatiles produced by the bacteria were determined in monoculture as well in pairwise combinations. Antimicrobial activity of the volatiles was assessed against fungal, oomycetal, and bacterial model organisms. Our results revealed that inter-specific bacterial interactions affected volatiles blend composition. Fungi and oomycetes showed high sensitivity to bacterial volatiles whereas the effect of volatiles on bacteria varied between no effects, growth inhibition to growth promotion depending on the volatile blend composition. In total 35 volatile compounds were detected most of which were sulfur-containing compounds. Two commonly produced sulfur-containing volatile compounds (dimethyl disulfide and dimethyl trisulfide) were tested for their effect on three target bacteria. Here, we display the importance of inter-specific interactions on bacterial volatiles production and their antimicrobial activities. PMID:26733959

The Effectiveness of WhatsApp Mobile Learning Activities Guided by Activity Theory on Students' Knowledge Management

ERIC Educational Resources Information Center

Barhoumi, Chokri

2015-01-01

This research paper explores the effectiveness of using mobile technologies to support a blended learning course titled Scientific Research Methods in Information Science. Specifically, it discusses the effects of WhatsApp mobile learning activities guided by activity theory on students' knowledge Management (KM). During the 2014 academic year,…

Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

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

Kurayoshi, Kenta; Ozono, Eiko; Iwanaga, Ritsuko

Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicidemore » gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter is activated by E2F only in cancer cells and therefore may be more cancer cell-specific than E2F1 promoter to drive gene expression. We show here that the ARF promoter has lower activity in normal growing fibroblasts and shows higher cancer cell-specificity compared to the E2F1 promoter. We also demonstrate that adenovirus expressing HSV-TK under the control of the ARF promoter shows lower cytotoxicity than that of the E2F1 promoter, in normal growing fibroblasts but has equivalent cytotoxicity in cancer cell lines. These results suggest that the ARF promoter, which is specifically activated by deregulated E2F activity, is an excellent candidate to drive therapeutic cytotoxic gene expression, specifically in cancer cells.« less

Factors other than light affecting the pineal gland: hypophysectomy, testosterone, dihydrotestosterone, estradiol, cryptorchidism, and stress

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

Urry, R.L.; Dougherty, K.A.; Frehn, J.L.

The article reviews those factors other than light that affect the activity of the pineal gland. Both testosterone and dihydroterosterone were shown to have tissue-specific inhibitory effects on pineal MAO activity concomitant with an increased activity of the gland. The effect also was tissue-specific. Bilateral and unilateral experimental cryptorchidism also decreased pineal MAO activity 3 to 4 weeks after surgery. Acute stresses appear to increase adrenal catecholamine output (epinephrine and norepinephrine) as well as to stimulate local adrenergic pathways, while chronic stress, such as starvation, appears to act through the adrenal corticosteroids by decreasing pineal MAO activity thereby indirectly increasingmore » melatonin synthesis. Thus, both components of the adrenal gland appear to act in concert to increase effectively melatonin synthesis by the pineal function----the latter specifically inhibits HIOMT activity. These observations indicate that many factors other than light affect pineal morphology and melatonin synthesis. The pineal appears to be a true neuroendocrine organ that is affected by hypophysectomy and is responsive to feedback and control from other organs within the mammalian organism. (auth)« less

Activity-Dependent Neurorehabilitation Beyond Physical Trainings: "Mental Exercise" Through Mirror Neuron Activation.

PubMed

Yuan, Ti-Fei; Chen, Wei; Shan, Chunlei; Rocha, Nuno; Arias-Carrión, Oscar; Paes, Flávia; de Sá, Alberto Souza; Machado, Sergio

2015-01-01

The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot make such efforts. Here the authors proposed the employment of mirror neurons system in promoting brain rehabilitation by "observation based stimulation". Mirror neuron system has been considered as an important basis for action understanding and learning by mimicking others. During the action observation, mirror neuron system mediated the direct activation of the same group of motor neurons that are responsible for the observed action. The effect is clear, direct, specific and evolutionarily conserved. Moreover, recent evidences hinted for the beneficial effects on stroke patients after mirror neuron system activation therapy. Finally some music-relevant therapies were proposed to be related with mirror neuron system.

Protein Stabilization and Enzyme Activation in Ionic Liquids: Specific Ion Effects

PubMed Central

Zhao, Hua

2015-01-01

There are still debates on whether the hydration of ions perturbs the water structure, and what is the degree of such disturbance; therefore, the origin of Hofmeister effect on protein stabilization continues being questioned. For this reason, it is suggested to use the ‘specific ion effect’ instead of other misleading terms such as Hofmeister effect, Hofmeister series, lyotropic effect, and lyotropic series. In this review, we firstly discuss the controversial aspect of inorganic ion effects on water structures, and several possible contributors to the specific ion effect of protein stability. Due to recent overwhelming attraction of ionic liquids (ILs) as benign solvents in many enzymatic reactions, we further evaluate the structural properties and molecular-level interactions in neat ILs and their aqueous solutions. Next, we systematically compare the specific ion effects of ILs on enzyme stability and activity, and conclude that (a) the specificity of many enzymatic systems in diluted aqueous IL solutions is roughly in line with the traditional Hofmeister series albeit some exceptions; (b) however, the specificity follows a different track in concentrated or neat ILs because other factors (such as hydrogen-bond basicity, nucelophilicity, and hydrophobicity, etc) are playing leading roles. In addition, we demonstrate some examples of biocatalytic reactions in IL systems that are guided by the empirical specificity rule. PMID:26949281

[Physical activity during pregnancy--facts and practical guidelines].

PubMed

Mor, Ron; Ben-Shlomo, Izhar

2014-08-01

Physical activity during pregnancy is known to have a positive effect on both the mother and the fetus/newborn, as long as there are no specific contraindications relating to maternal pathology. Physical activity during pregnancy is known to be associated with reduced incidence of several gestational pathologies, as well as boosting physical and mental capabilities. Furthermore, a positive effect was found in newborns whose mothers continued their physical activity habits throughout pregnancy. Nevertheless, the intensity and duration, and specifically their efforts against resistance, have not been adequately emphasized. Herein, we review the main recent findings and insights on physical activity during pregnancy, and provide a practical set of recommendations.

Enzymatic and antisense effects of a specific anti-Ki-ras ribozyme in vitro and in cell culture.

PubMed Central

Giannini, C D; Roth, W K; Piiper, A; Zeuzem, S

1999-01-01

Due to their mode of action, ribozymes show antisense effects in addition to their specific cleavage activity. In the present study we investigated whether a hammerhead ribozyme is capable of cleaving mutated Ki-ras mRNA in a pancreatic carcinoma cell line and whether antisense effects contribute to the activity of the ribozyme. A 2[prime]-O-allyl modified hammerhead ribozyme was designed to cleave specifically the mutated form of the Ki- ras mRNA (GUU motif in codon 12). The activity was monitored by RT-PCR on Ki- ras RNA expression by determination of the relative amount of wild type to mutant Ki-ras mRNA, by 5-bromo-2[prime]-deoxy-uridine incorporation on cell proliferation and by colony formation in soft agar on malignancy in the human pancreatic adenocarcinoma cell line CFPAC-1, which is heterozygous for the Ki-ras mutation. A catalytically inactive ribozyme was used as control to differentiate between antisense and cleavage activity and a ribozyme with random guide sequences as negative control. The catalytically active anti-Ki-ras ribozyme was at least 2-fold more potent in decreasing cellular Ki-ras mRNA levels, inhibiting cell proliferation and colony formation in soft agar than the catalytically inactive ribozyme. The catalytically active anti-Ki-ras ribozyme, but not the catalytically inactive or random ribozyme, increased the ratio of wild type to mutated Ki-ras mRNA in CFPAC-1 cells. In conclusion, both cleavage activity and antisense effects contribute to the activity of the catalytically active anti-Ki-ras hammerhead ribozyme. Specific ribozymes might be useful in the treatment of pancreatic carcinomas containing an oncogenic GTT mutation in codon 12 of the Ki-ras gene. PMID:10373591

Modalities of Thinking: State and Trait Effects on Cross-Frequency Functional Independent Brain Networks.

PubMed

Milz, Patricia; Pascual-Marqui, Roberto D; Lehmann, Dietrich; Faber, Pascal L

2016-05-01

Functional states of the brain are constituted by the temporally attuned activity of spatially distributed neural networks. Such networks can be identified by independent component analysis (ICA) applied to frequency-dependent source-localized EEG data. This methodology allows the identification of networks at high temporal resolution in frequency bands of established location-specific physiological functions. EEG measurements are sensitive to neural activity changes in cortical areas of modality-specific processing. We tested effects of modality-specific processing on functional brain networks. Phasic modality-specific processing was induced via tasks (state effects) and tonic processing was assessed via modality-specific person parameters (trait effects). Modality-specific person parameters and 64-channel EEG were obtained from 70 male, right-handed students. Person parameters were obtained using cognitive style questionnaires, cognitive tests, and thinking modality self-reports. EEG was recorded during four conditions: spatial visualization, object visualization, verbalization, and resting. Twelve cross-frequency networks were extracted from source-localized EEG across six frequency bands using ICA. RMANOVAs, Pearson correlations, and path modelling examined effects of tasks and person parameters on networks. Results identified distinct state- and trait-dependent functional networks. State-dependent networks were characterized by decreased, trait-dependent networks by increased alpha activity in sub-regions of modality-specific pathways. Pathways of competing modalities showed opposing alpha changes. State- and trait-dependent alpha were associated with inhibitory and automated processing, respectively. Antagonistic alpha modulations in areas of competing modalities likely prevent intruding effects of modality-irrelevant processing. Considerable research suggested alpha modulations related to modality-specific states and traits. This study identified the distinct electrophysiological cortical frequency-dependent networks within which they operate.

The effect of visual scanning exercises integrated into physiotherapy in patients with unilateral spatial neglect poststroke: a matched-pair randomized control trial.

PubMed

van Wyk, Andoret; Eksteen, Carina A; Rheeder, Paul

2014-01-01

Unilateral spatial neglect (USN) is a visual-perceptual disorder that entails the inability to perceive and integrate stimuli on one side of the body, resulting in the neglect of one side of the body. Stroke patients with USN present with extensive functional disability and duration of therapy input. To determine the effect of saccadic eye movement training with visual scanning exercises (VSEs) integrated with task-specific activities on USN poststroke. A matched-pair randomized control trial was conducted. Subjects were matched according to their functional activity level and allocated to either a control (n = 12) or an experimental group (n = 12). All patients received task-specific activities for a 4-week intervention period. The experimental group received saccadic eye movement training with VSE integrated with task specific activities as an "add on" intervention. Assessments were conducted weekly over the intervention period. Statistical significant difference was noted on the King-Devick Test (P = .021), Star Cancellation Test (P = .016), and Barthel Index (P = .004). Intensive saccadic eye movement training with VSE integrated with task-specific activities has a significant effect on USN in patients poststroke. Results of this study are supported by findings from previously reviewed literature in the sense that the effect of saccadic eye movement training with VSE as an intervention approach has a significant effect on the visual perceptual processing of participants with USN poststroke. The significant improved visual perceptual processing translate to significantly better visual function and ability to perform activities of daily living following the stroke. © The Author(s) 2014.

Correlation between hepatocarcinogenic effect of estragole and its influence on glucocorticoid induction of liver-specific enzymes and activities of FOXA and HNF4 transcription factors in mouse and rat liver.

PubMed

Kaledin, V I; Pakharukova, M Yu; Pivovarova, E N; Kropachev, K Yu; Baginskaya, N V; Vasilieva, E D; Ilnitskaya, S I; Nikitenko, E V; Kobzev, V F; Merkulova, T I

2009-04-01

It is known that the carcinogenic effect of estragole, a component of essential oils of many spicy plants, is characterized by species, tissue, and sex specificity. It causes mainly liver tumors in female mice but is not carcinogenic for male mice and for rats. In this work, the estragole hepatocarcinogenicity was shown for female mice of previously not studied ICR line. The strict correlation between estragole hepatocarcinogenicity and its ability to decrease the level of glucocorticoid induction of liver-specific enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) was found. Inhibition of TAT and TO inducibility by estragole takes place only in female mice but not in male mice and in rats. Studying the estragole effect on DNA-binding activity of transcription factors, present mainly in liver and regulating expression of genes encoding liver-specific proteins, has shown that estragole decreases FOXA and HNF4 activities but not activities of C/EBP and HNF1, and this happens only in female mice, for which this substance is hepatocarcinogen, but not in male mice and in rats. Pentachlorophenol, preventing hepatocarcinogenic effect of estragole, abolishes inhibitory influence of the latter on the TAT and TO glucocorticoid induction and restores DNA-binding activity of FOXA and HNF4. Thus, a correlation was revealed between the estragole hepatocarcinogenic effect and decrease in DNA-binding activity of transcription factors FOXA and HNF4, which might be indicative of the role of these factors in tumor suppression mechanisms in liver.

38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

38 CFR 3.374 - Effect of diagnosis of active tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... active tuberculosis. 3.374 Section 3.374 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Considerations Relative to Specific Diseases § 3.374 Effect of diagnosis of active tuberculosis. (a) Service diagnosis. Service department diagnosis of active pulmonary tuberculosis will be accepted unless a board of...

What Are the Most Effective Intervention Techniques for Changing Physical Activity Self-Efficacy and Physical Activity Behaviour--and Are They the Same?

ERIC Educational Resources Information Center

Williams, S. L.; French, D. P.

2011-01-01

There is convincing evidence that targeting self-efficacy is an effective means of increasing physical activity. However, evidence concerning which are the most effective techniques for changing self-efficacy and thereby physical activity is lacking. The present review aims to estimate the association between specific intervention techniques used…

Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system

PubMed Central

Kim, Teayoun; Yang, Qinglin

2013-01-01

Peroxisome-proliferator-activated receptors (PPARs) comprise three subtypes (PPARα, δ and γ) to form a nuclear receptor superfamily. PPARs act as key transcriptional regulators of lipid metabolism, mitochondrial biogenesis, and anti-oxidant defense. While their roles in regulating lipid metabolism have been well established, the role of PPARs in regulating redox activity remains incompletely understood. Since redox activity is an integral part of oxidative metabolism, it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state. The effects of PPAR signaling are directly related to PPAR expression, protein activities and PPAR interactions with their coregulators. The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue. Adding to the complexity, specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways. Moreover, the intensity and extension of redox regulation by each PPAR subtype are varied depending on different tissues and cell types. Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups. The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms, as well as to discuss the implications in the cardiovascular system. PMID:23802046

Recall versus familiarity when recall fails for words and scenes: The differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions☆

PubMed Central

Ryals, Anthony J.; Cleary, Anne M.; Seger, Carol A.

2013-01-01

This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. PMID:23142268

A Study on Situated Cognition: Product Dissection's Effect on Redesign Activities

ERIC Educational Resources Information Center

Grantham, Katie; Okudan Kremer, Gül E.; Simpson, Timothy W.; Ashour, Omar

2013-01-01

Situated cognition theory describes the context of a learning activity's effect on learner's cognition. In this paper, we use situated cognition theory to examine the effect of product dissection on product redesign activities. Two specific research questions are addressed: 1) Does situated cognition, in the form of product dissection, improve…

Functional versus effector-specific organization of the human posterior parietal cortex: revisited

PubMed Central

Leone, Frank T. M.; Medendorp, W. Pieter

2016-01-01

It has been proposed that the posterior parietal cortex (PPC) is characterized by an effector-specific organization. However, strikingly similar functional MRI (fMRI) activation patterns have been found in the PPC for hand and foot movements. Because the fMRI signal is related to average neuronal activity, similar activation levels may result either from effector-unspecific neurons or from intermingled subsets of effector-specific neurons within a voxel. We distinguished between these possibilities using fMRI repetition suppression (RS). Participants made delayed, goal-directed eye, hand, and foot movements to visual targets. In each trial, the instructed effector was identical or different to that of the previous trial. RS effects indicated an attenuation of the fMRI signal in repeat trials. The caudal PPC was active during the delay but did not show RS, suggesting that its planning activity was effector independent. Hand and foot-specific RS effects were evident in the anterior superior parietal lobule (SPL), extending to the premotor cortex, with limb overlap in the anterior SPL. Connectivity analysis suggested information flow between the caudal PPC to limb-specific anterior SPL regions and between the limb-unspecific anterior SPL toward limb-specific motor regions. These results underline that both function and effector specificity should be integrated into a concept of PPC action representation not only on a regional but also on a fine-grained, subvoxel level. PMID:27466132

P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.

PubMed

Hostettler, Nina; Naggi, Annamaria; Torri, Giangiacomo; Ishai-Michaeli, Riva; Casu, Benito; Vlodavsky, Israel; Borsig, Lubor

2007-11-01

Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we identified modified, nonanticoagulant species of heparin that specifically inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity, or both. We show that selective inhibition of selectin interactions or heparanase with specific heparin derivatives in mouse models of MC-38 colon carcinoma and B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had no effect, in accordance with the virtual absence of heparanase activity in these cells. Heparin derivatives had no further effect on metastasis in mice deficient in P- and L-selectin, indicating that selectins are the primary targets of heparin antimetastatic activity. Selectin-specific and heparanase-specific derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When mice were injected with a derivative containing both heparanase and selectin inhibitory activity, no additional attenuation of metastasis could be observed. Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of both tumor cell types whereas inhibition of heparanase led to reduction of metastasis only in tumor cells producing heparanase.

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2012 CFR

2012-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2011 CFR

2011-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2014 CFR

2014-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2013 CFR

2013-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

Baicalin and scutellarin are proteasome inhibitors that specifically target chymotrypsin-like catalytic activity.

PubMed

Wu, Yi-Xin; Sato, Eiji; Kimura, Wataru; Miura, Naoyuki

2013-09-01

Baicalin and scutellarin are the major active principal flavonoids extracted from the Chinese herbal medicines Scutellaria baicalensis and Erigeron breviscapus (Vant.) Hand-Mazz. It has recently been reported that baicalin and scutellarin have antitumor activity. However, the mechanisms of action are unknown. We previously reported that some flavonoids have a specific role in the inhibition of the activity of proteasome subunits and induced apoptosis in tumor cells. To further investigate these pharmacological effects, we examined the inhibitory activity of baicalin and scutellarin on the extracted proteasomes from mice and cancer cells. Using fluorogenic substrates for proteasome catalytic subunits, we found that baicalin and scutellarin specifically inhibited chymotrypsin-like activity but did not inhibit trypsin-like and peptidyl-glutamyl peptide hydrolyzing activities. These data suggested that baicalin and scutellarin specifically inhibit chymotrypsin-like catalytic activity in the proteasome. Copyright © 2012 John Wiley & Sons, Ltd.

A model to assess lactic acid bacteria aminopeptidase activities in Parmigiano Reggiano cheese during ripening.

PubMed

Gatti, M; De Dea Lindner, J; Gardini, F; Mucchetti, G; Bevacqua, D; Fornasari, M E; Neviani, E

2008-11-01

The aim of this work was to investigate in which phases of ripening of Parmigiano Reggiano cheese lactic acid bacteria aminopeptidases present in cheese extract could be involved in release of free amino acids and to better understand the behavior of these enzymes in physical-chemical conditions that are far from their optimum. In particular, we evaluated 6 different substrates to reproduce broad-specificity aminopeptidase N, broad-specificity aminopeptidase C, glutamyl aminopeptidase A, peptidase with high specificity for leucine and alanine, proline iminopeptidase, and X-prolyl dipeptidyl aminopeptidase activities releasing different N-terminal amino acids. The effects of pH, NaCl concentration, and temperature on the enzyme activities of amino acid beta-naphthylamide (betaNA)-substrates were determined by modulating the variables in 19 different runs of an experimental design, which allowed the building of mathematical models able to assess the effect on aminopeptidases activities over a range of values, obtained with bibliographic data, covering different environmental conditions in different zones of the cheese wheel at different aging times. The aminopeptidases tested in this work were present in cell-free Parmigiano Reggiano cheese extract after a 17-mo ripening and were active when tested in model system. The modeling approach shows that to highlight the individual and interactive effects of chemical-physical variables on enzyme activities, it is helpful to determine the true potential of an amino-peptidase in cheese. Our results evidenced that the 6 different lactic acid bacteria peptidases participate in cheese proteolysis and are induced or inhibited by the cheese production parameters that, in turn, depend on the cheese dimension. Generally, temperature and pH exerted the more relevant effects on the enzymatic activities, and in many cases, a relevant interactive effect of these variables was observed. Increasing salt concentration slowed down broad-specificity amino-peptidase C, glutamyl aminopeptidase A, proline iminopeptidase, and peptidase with high specificity for leucine and alanine. Interestingly, this variable did not affect broad-specificity aminopeptidase N and positively affected X-prolyl dipeptidyl aminopeptidase. The models elaborated varying pH, temperatures, and salt concentration and were a useful, low cost, and fast tool to understand the role of the main peptidases in the different phases of cheese ripening in relation to the major environmental factors influencing enzyme activity.

Spatial distribution and vertical migration of (137)Cs in soils of Belgrade (Serbia) 25 years after the Chernobyl accident.

PubMed

Petrović, Jelena; Ćujić, Mirjana; Đorđević, Milan; Dragović, Ranko; Gajić, Boško; Miljanić, Šćepan; Dragović, Snežana

2013-06-01

In this study, the specific activity of (137)Cs was determined by gamma-ray spectrometry in 72 surface soil samples and 11 soil profiles collected from the territory of Belgrade 25 years after the Chernobyl accident. Based on the data obtained the external effective gamma dose rates due to (137)Cs were assessed and geographically mapped. The influence of pedogenic factors (pH, specific electrical conductivity, cation exchange capacity, organic matter content, soil particle size and carbonate content) on the spatial and vertical distribution of (137)Cs in soil was estimated through Pearson correlations. The specific activity of (137)Cs in surface soil samples ranged from 1.00 to 180 Bq kg(-1), with a mean value of 29.9 Bq kg(-1), while in soil profiles they ranged from 0.90 to 58.0 Bq kg(-1), with a mean value of 15.3 Bq kg(-1). The mean external effective gamma dose at 1 m above the ground due to (137)Cs in the soil was calculated to be 1.96 nSv h(-1). Geographic mapping of the external effective gamma dose rates originating from (137)Cs revealed much higher dose rates in southern parts of Belgrade city and around the confluence of the Sava and Danube. Negative Pearson correlation coefficients were found between pH, cation exchange capacity and (137)Cs specific activity in surface soil. There were positive correlations between organic matter and (137)Cs specific activity in surface soil; and between specific electrical conductivity, organic matter, silt content and (137)Cs specific activity in soil profiles.

Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large scale mammalian pharmacological dataset

EPA Science Inventory

To proceed in the investigation of potential effects of thousands of active pharmaceutical ingredients (API) which may enter the aquatic environment, a cohesive research strategy, specifically a prioritization is paramount. API are biologically active, with specific physiologica...

Evaluation of Toxic Effects of Aeration and Trichloroethylene Oxidation on Methanotrophic Bacteria Grown with Different Nitrogen Sources

PubMed Central

Chu, Kung-Hui; Alvarez-Cohen, Lisa

1999-01-01

In this study we evaluated specific and nonspecific toxic effects of aeration and trichloroethylene (TCE) oxidation on methanotrophic bacteria grown with different nitrogen sources (nitrate, ammonia, and molecular nitrogen). The specific toxic effects, exerted directly on soluble methane monooxygenase (sMMO), were evaluated by comparing changes in methane uptake rates and naphthalene oxidation rates following aeration and/or TCE oxidation. Nonspecific toxic effects, defined as general cellular damage, were examined by using a combination of epifluorescent cellular stains to measure viable cell numbers based on respiratory activity and measuring formate oxidation activities following aeration and TCE transformation. Our results suggest that aeration damages predominantly sMMO rather than other general cellular components, whereas TCE oxidation exerts a broad range of toxic effects that damage both specific and nonspecific cellular functions. TCE oxidation caused sMMO-catalyzed activity and respiratory activity to decrease linearly with the amount of substrate degraded. Severe TCE oxidation toxicity resulted in total cessation of the methane, naphthalene, and formate oxidation activities and a 95% decrease in the respiratory activity of methanotrophs. The failure of cells to recover even after 7 days of incubation with methane suggests that cellular recovery following severe TCE product toxicity is not always possible. Our evidence suggests that generation of greater amounts of sMMO per cell due to nitrogen fixation may be responsible for enhanced TCE oxidation activities of nitrogen-fixing methanotrophs rather than enzymatic protection mechanisms associated with the nitrogenase enzymes. PMID:9925614

Enhancing learning in geosciences and water engineering via lab activities

NASA Astrophysics Data System (ADS)

Valyrakis, Manousos; Cheng, Ming

2016-04-01

This study focuses on the utilisation of lab based activities to enhance the learning experience of engineering students studying Water Engineering and Geosciences. In particular, the use of modern highly visual and tangible presentation techniques within an appropriate laboratory based space are used to introduce undergraduate students to advanced engineering concepts. A specific lab activity, namely "Flood-City", is presented as a case study to enhance the active engagement rate, improve the learning experience of the students and better achieve the intended learning objectives of the course within a broad context of the engineering and geosciences curriculum. Such activities, have been used over the last few years from the Water Engineering group @ Glasgow, with success for outreach purposes (e.g. Glasgow Science Festival and demos at the Glasgow Science Centre and Kelvingrove museum). The activity involves a specific setup of the demonstration flume in a sand-box configuration, with elements and activities designed so as to gamely the overall learning activity. Social media platforms can also be used effectively to the same goals, particularly in cases were the students already engage in these online media. To assess the effectiveness of this activity a purpose designed questionnaire is offered to the students. Specifically, the questionnaire covers several aspects that may affect student learning, performance and satisfaction, such as students' motivation, factors to effective learning (also assessed by follow-up quizzes), and methods of communication and assessment. The results, analysed to assess the effectiveness of the learning activity as the students perceive it, offer a promising potential for the use of such activities in outreach and learning.

Stereotypic wheel running decreases cortical activity in mice

PubMed Central

Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

2016-01-01

Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

Novel Opioid Analgesics and Side Effects.

PubMed

Del Vecchio, Giovanna; Spahn, Viola; Stein, Christoph

2017-08-16

Conventional opioids mediate analgesia as well as severe adverse effects via G-protein coupled opioid receptors (OR) in both inflamed (peripheral injured tissue) and healthy (brain, intestinal wall) environments. To exclude side effects, OR activation can be selectively achieved in damaged tissue by lowering the pK a of an opioid ligand to the acidic pH of inflammation. As a result, protonation of the ligand and consequent OR binding and activation of G-proteins is pH- and injury-specific. A novel compound (NFEPP) demonstrates the feasibility of this approach and displays blockade of pain transmission only at the peripheral site of injury, but with lack of central and gastrointestinal adverse effects. These findings suggest disease-specific receptor activation as a new strategy in drug design.

Comprehensive Interrogation of Natural TALE DNA Binding Modules and Transcriptional Repressor Domains

PubMed Central

Cong, Le; Zhou, Ruhong; Kuo, Yu-chi; Cunniff, Margaret; Zhang, Feng

2012-01-01

Transcription activator-like effectors (TALE) are sequence-specific DNA binding proteins that harbor modular, repetitive DNA binding domains. TALEs have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the TALE toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat variable diresidue (RVD) Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective TALE transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using TALEs. PMID:22828628

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

PubMed

Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

2007-05-01

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

PubMed Central

Ahn, Jeonghyun; Ko, Ara; Jun, Eun Jung; Won, Minah; Kim, Yoo Kyum; Ju, Eun-Seon

2012-01-01

Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases. PMID:22508300

Regulation of the activity and fatty acid specificity of lecithin-cholesterol acyltransferase by sphingomyelin, and its metabolites ceramide and ceramide phosphate†

PubMed Central

Subbaiah, Papasani V.; Horvath, Peter; Achar, Srinivasa B.

2006-01-01

Sphingomyelin (SM), the second most abundant phospholipid in plasma lipoproteins, was previously shown to be a physiological inhibitor of the lecithin-cholesterol acyltransferase (LCAT) reaction. In this study, we investigated the effects of its metabolites, ceramide and ceramide phosphate, on the activity and fatty acid specificity of LCAT in vitro. Treatment of SM-containing substrate with SMase C, which hydrolyzes SM to ceramide, abolished the inhibitory effect of SM, whereas treatment with SMase D, which hydrolyzes it to ceramide phosphate, increased the inhibition. Although incorporation of ceramide into the substrate in the absence of SM activated the LCAT reaction only modestly, its co-incorporation with SM neutralized the inhibitory effect of SM. Ceramide phosphate, on the other hand, inhibited the LCAT reaction more strongly than SM. The effects of the sphingolipids were similar on the phospholipase A and cholesterol esterification reactions of the enzyme, indicating that they regulate the binding of phosphatidylcholine (PC) to the active site, rather than the esterification step. Ceramide incorporation into the substrate stimulated the synthesis of unsaturated cholesteryl esters at the expense of saturated esters. However these effects on fatty acid specificity disappeared when the PC substrates were incorporated into an inert diether PC matrix, suggesting that ceramide increases the availability of polyunsaturated PCs to the enzyme by altering the macromolecular structure of the substrate particle. Since the plasma ceramide levels are increased during inflammation, these results indicate that the activity and fatty acid specificity of LCAT may be altered during the inflammatory response. PMID:16605271

The effect of inhibitory signals on the priming of drug-hapten-specific T-cells that express distinct Vβ receptors

PubMed Central

Gibson, Andrew; Faulkner, Lee; Lichtenfels, Maike; Ogese, Monday; Al-Attar, Zaid; Alfirevic, Ana; Esser, Philipp R.; Martin, Stefan F.; Pirmohamed, Munir; Park, B. Kevin; Naisbitt, Dean J.

2017-01-01

Drug hypersensitivity involves the activation of T-cells in an HLA allele-restricted manner. Since the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T-cell response. Thus, we have utilized a T-cell priming assay and nitroso sulfamethoxazole (SMX-NO) as a model antigen to investigate (1) the activation of specific T-cell receptor (TCR)Vβ subtypes, (2) the impact of PD-1, CTLA4 and TIM-3 co-inhibitory signalling on activation of naïve and memory T-cells and (3) the ability of Tregs to prevent responses. An expansion of the TCR repertoire was observed for nine different Vβ subtypes, while spectratyping revealed that SMX-NO-specific T-cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ-restricted antigen-specific T-cell responses is governed by regulatory signals. Blockade of PDL-1/CTLA4 signalling dampened activation of SMX-NO-specific naïve and memory T-cells, while blockade of TIM-3 produced no effect. PD-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T-cell activation and expression of each receptor was enhanced on dividing T-cells. As these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO-induced T-cell activation was investigated. Tregs significantly dampened the priming of T-cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of co-inhibitory signalling pathways and dysfunctional Tregs may influence predisposition to hypersensitivity. PMID:28687658

Recall versus familiarity when recall fails for words and scenes: the differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions.

PubMed

Ryals, Anthony J; Cleary, Anne M; Seger, Carol A

2013-01-25

This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. Copyright © 2012 Elsevier B.V. All rights reserved.

Bee Venom (Apis Mellifera) an Effective Potential Alternative to Gentamicin for Specific Bacteria Strains: Bee Venom an Effective Potential for Bacteria.

PubMed

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2016-09-01

Mellitine, a major component of bee venom (BV, Apis mellifera ), is more active against gram positive than gram negative bacteria. Moreover, BV has been reported to have multiple effects, including antibacterial, antivirus, and anti-inflammation effects, in various types of cells. In addition, wasp venom has been reported to have antibacterial properties. The aim of this study was to evaluate the antibacterial activity of BV against selected gram positive and gram negative bacterial strains of medical importance. This investigation was set up to evaluate the antibacterial activity of BV against six grams positive and gram negative bacteria, including Staphylococcus aureus ( S. aureus ), Salmonella typhimurium , Escherichia coli ( E. coli ) O157:H7, Pseudomonas aeruginosa , Burkholderia mallei and Burkholderia pseudomallei. Three concentrations of crude BV and standard antibiotic (gentamicin) disks as positive controls were tested by using the disc diffusion method. BV was found to have a significant antibacterial effect against E. coli , S. aureus , and Salmonella typhyimurium in all three concentrations tested. However, BV had no noticeable effect on other tested bacteria for any of the three doses tested. The results of the current study indicate that BV inhibits the growth and survival of bacterial strains and that BV can be used as a complementary antimicrobial agent against pathogenic bacteria. BV lacked the effective proteins necessary for it to exhibit antibacterial activity for some specific strains while being very effective against other specific strains. Thus, one may conclude, that Apis mellifera venom may have a specific mechanism that allows it to have an antibacterial effect on certain susceptible bacteria, but that mechanism is not well understood.

INTRACELLULAR SIGNALING BY BILE ACIDS

PubMed Central

Anwer, Mohammed Sawkat

2014-01-01

Bile acids, synthesized from cholesterol, are known to produce beneficial as well as toxic effects in the liver. The beneficial effects include choleresis, immunomodulation, cell survival, while the toxic effects include cholestasis, apoptosis and cellular toxicity. It is believed that bile acids produce many of these effects by activating intracellular signaling pathways. However, it has been a challenge to relate intracellular signaling to specific and at times opposing effects of bile acids. It is becoming evident that bile acids produce different effects by activating different isoforms of phosphoinositide 3-kinase (PI3K), Protein kinase Cs (PKCs), and mitogen activated protein kinases (MAPK). Thus, the apoptotic effect of bile acids may be mediated via PI3K-110γ, while cytoprotection induce by cAMP-GEF pathway involves activation of PI3K-p110α/β isoforms. Atypical PKCζ may mediate beneficial effects and nPKCε may mediate toxic effects, while cPKCα and nPKCδ may be involved in both beneficial and toxic effects of bile acids. The opposing effects of nPKCδ activation may depend on nPKCδ phosphorylation site(s). Activation of ERK1/2 and JNK1/2 pathway appears to mediate beneficial and toxic effects, respectively, of bile acids. Activation of p38α MAPK and p38β MAPK may mediate choleretic and cholestatic effects, respectively, of bile acids. Future studies clarifying the isoform specific effects on bile formation should allow us to define potential therapeutic targets in the treatment of cholestatic disorders. PMID:25378891

Analysis of the biological activity of antilymphocyte serum

PubMed Central

Perper, R. J.; Monovich, R. E.; Van Gorder, T. J.

1971-01-01

Two IgG subfractions of horse antilymphocyte serum (ALS) were obtained by DEAE Sephadex chromatography. Although the fractions did not differ antigenically, they differed on amino acid and carbohydrate analysis, and in electrophoretic mobility. As demonstrated by binding studies, only the most positively charged population of IgG molecules (fraction 1) obtained from anti-lymphocyte serum had specificity for the small lymphocyte; 50 per cent of the molecules in this population bound specifically to lymphocytes in vitro. As determined by an in vitro correlate of immunosuppressive potency (rosette inhibition), fraction 1 (F1) IgG from ALS contained approximately 4 times the specific activity of fraction 2 (F2). F1 was significantly more effective in prolonging skin graft survival than F2, whereas F2 contained the major component of the non-specific anti-inflammatory activity of serum. The anti-inflammatory effect was mediated by anticomplement activity. F2 was found to be an effective inhibitor of the immunosuppressive activity of F1 both in vivo and in vitro. Quantitative studies indicated that 1 part of F2 could maximally inhibit 4 parts of F1. The percentage of F2 present in serum IgG was inversely related to the skin graft survival elicited by the serum, which indicated that F2 was active as an inhibitor when tested as purified fraction as well as in unfractionated serum. Following immunization when F1 gained immunosuppressive potency, it lost non-specific anti-inflammatory activity. These observations indicated that not only was there a quantitative, as well as a qualitative concentration of immunosuppressive antibodies in F1, but also that this activity was controlled by the concentration of F2. This report, therefore, describes an IgG control mechanism which can limit the expression of antibody induced biological activity. It is suggested that in ALS the immunosuppressive antibody molecules possess a greater net positive charge than the remaining population, and that this is due to the degree of the negative charge on the immunizing antigen. Using DEAE Sephadex chromatography, these populations could be separated into two differently charged populations of molecules, only one of which had significant immunosuppressive capability. This increase in activity resulted from the increase of specific molecules, the loss of non-specific molecules, and was manifest upon the removal of an IgG inhibitor. ImagesFIG. 1FIG. 2 PMID:4943146

Selective Control of Fear Expression by Optogenetic Manipulation of Infralimbic Cortex after Extinction

PubMed Central

Kim, Hyung-Su; Cho, Hye-Yeon; Augustine, George J; Han, Jin-Hee

2016-01-01

Evidence from rodent and human studies has identified the ventromedial prefrontal cortex, specifically the infralimbic cortex (IL), as a critical brain structure in the extinction of conditioned fear. However, how IL activity controls fear expression at the time of extinction memory retrieval is unclear and controversial. To address this issue, we used optogenetics to precisely manipulate the activity of genetically targeted cells and to examine the real-time contribution of IL activity to expression of auditory-conditioned fear extinction in mice. We found that inactivation of IL, but not prelimbic cortex, impaired extinction retrieval. Conversely, photostimulation of IL excitatory neurons robustly enhanced the inhibition of fear expression after extinction, but not before extinction. Moreover, this effect was specific to the conditioned stimulus (CS): IL activity had no effect on expression of fear in response to the conditioned context after auditory fear extinction. Thus, in contrast to the expectation from a generally held view, artificial activation of IL produced no significant effect on expression of non-extinguished conditioned fear. Therefore, our data provide compelling evidence that IL activity is critical for expression of fear extinction and establish a causal role for IL activity in controlling fear expression in a CS-specific manner after extinction. PMID:26354044

Specific Activation of the Plant P-type Plasma Membrane H+-ATPase by Lysophospholipids Depends on the Autoinhibitory N- and C-terminal Domains.

PubMed

Wielandt, Alex Green; Pedersen, Jesper Torbøl; Falhof, Janus; Kemmer, Gerdi Christine; Lund, Anette; Ekberg, Kira; Fuglsang, Anja Thoe; Pomorski, Thomas Günther; Buch-Pedersen, Morten Jeppe; Palmgren, Michael

2015-06-26

Eukaryotic P-type plasma membrane H(+)-ATPases are primary active transport systems that are regulated at the post-translation level by cis-acting autoinhibitory domains, which can be relieved by protein kinase-mediated phosphorylation or binding of specific lipid species. Here we show that lysophospholipids specifically activate a plant plasma membrane H(+)-ATPase (Arabidopsis thaliana AHA2) by a mechanism that involves both cytoplasmic terminal domains of AHA2, whereas they have no effect on the fungal counterpart (Saccharomyces cerevisiae Pma1p). The activation was dependent on the glycerol backbone of the lysophospholipid and increased with acyl chain length, whereas the headgroup had little effect on activation. Activation of the plant pump by lysophospholipids did not involve the penultimate residue, Thr-947, which is known to be phosphorylated as part of a binding site for activating 14-3-3 protein, but was critically dependent on a single autoinhibitory residue (Leu-919) upstream of the C-terminal cytoplasmic domain in AHA2. A corresponding residue is absent in the fungal counterpart. These data indicate that plant plasma membrane H(+)-ATPases evolved as specific receptors for lysophospholipids and support the hypothesis that lysophospholipids are important plant signaling molecules. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

In vitro evaluation of cross-strain inhibitory effects of IgY polyclonal antibody against H. pylori.

PubMed

Solhi, Roya; Alebouyeh, Masoud; Khafri, Abolfazl; Rezaeifard, Morteza; Aminian, Mahdi

2017-09-01

The present study aimed to evaluate in vitro cross-strain inhibitory effects of IgY polyclonal antibody on both growth and urease enzyme of four local strains of H. pylori. Leghorn chickens were immunized with whole cells of four different strains of H. pylori, separately. Rising of specific IgY was detected by ELISA. The IgY purified using polyethylene glycol method and the purity was evaluated by SDS-PAGE and Western blotting. Each strain was treated with its own-specific and also other strain-specific IgYs. The strain-specific IgY could inhibit the growth of specific strains by 49-72% and also other different strains of H. pylori by 29-86%. Our findings revealed that strain-specific IgY could inhibit urease activity of its own by 64-72% and other different strains by 49-79%. These findings confirmed strain-specific and also cross-strain inhibitory effects of the IgY polyclonal antibody on both growth and urease activity of H. pylori. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Verapamil Analogs Inhibit Intracellular Mycobacteria without Affecting the Functions of Mycobacterium-Specific T Cells

PubMed Central

Ruminiski, Peter G.; Kumar, Malkeet; Singh, Kawaljit; Hamzabegovic, Fahreta; Hoft, Daniel F.; Eickhoff, Christopher S.; Selimovic, Asmir; Campbell, Mary; Chibale, Kelly

2015-01-01

There is a growing interest in repurposing mycobacterial efflux pump inhibitors, such as verapamil, for tuberculosis (TB) treatment. To aid in the design of better analogs, we studied the effects of verapamil on macrophages and Mycobacterium tuberculosis-specific T cells. Macrophage activation was evaluated by measuring levels of nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and gamma interferon (IFN-γ). Since verapamil is a known autophagy inducer, the roles of autophagy induction in the antimycobacterial activities of verapamil and norverapamil were studied using bone marrow-derived macrophages from ATG5flox/flox (control) and ATG5flox/flox Lyz-Cre mice. Our results showed that despite the well-recognized effects of verapamil on calcium channels and autophagy, its action on intracellular M. tuberculosis does not involve macrophage activation or autophagy induction. Next, the effects of verapamil and norverapamil on M. tuberculosis-specific T cells were assessed using flow cytometry following the stimulation of peripheral blood mononuclear cells from TB-skin-test-positive donors with M. tuberculosis whole-cell lysate for 7 days in the presence or absence of drugs. We found that verapamil and norverapamil inhibit the expansion of M. tuberculosis-specific T cells. Additionally, three new verapamil analogs were found to inhibit intracellular Mycobacterium bovis BCG, and one of the three analogs (KSV21) inhibited intracellular M. tuberculosis replication at concentrations that did not inhibit M. tuberculosis-specific T cell expansion. KSV21 also inhibited mycobacterial efflux pumps to the same degree as verapamil. More interestingly, the new analog enhances the inhibitory activities of isoniazid and rifampin on intracellular M. tuberculosis. In conclusion, KSV21 is a promising verapamil analog on which to base structure-activity relationship studies aimed at identifying more effective analogs. PMID:26643325

Differentiating pathway-specific from nonspecific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

EPA Science Inventory

The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential ...

Associations among workplace environment, self-regulation, and domain-specific physical activities among white-collar workers: a multilevel longitudinal study.

PubMed

Watanabe, Kazuhiro; Kawakami, Norito; Otsuka, Yasumasa; Inoue, Shigeru

2018-05-31

Psychological and environmental determinants have been discussed for promoting physical activity among workers. However, few studies have investigated effects of both workplace environment and psychological determinants on physical activity. It is also unknown which domains of physical activities are promoted by these determinants. This study aimed to investigate main and interaction effects of workplace environment and individual self-regulation for physical activity on domain-specific physical activities among white-collar workers. A multi-site longitudinal study was conducted at baseline and about 5-month follow-up. A total of 49 worksites and employees within the worksites were recruited. Inclusion criteria for the worksites (a) were located in the Kanto area, Japan and (b) employed two or more employees. Employee inclusion criteria were (a) employed by the worksites, (b) aged 18 years or older, and (c) white-collar workers. For outcomes, three domain-specific physical activities (occupational, transport-related, and leisure-time) at baseline and follow-up were measured. For independent variables, self-regulation for physical activity, workplace environments (parking/bike, signs/bulletin boards/advertisements, stairs/elevators, physical activity/fitness facilities, work rules, written policies, and health promotion programs), and covariates at baseline were measured. Hierarchical Linear Modeling was conducted to investigate multilevel associations. Of the recruited worksites, 23 worksites and 562 employees, and 22 worksites and 459 employees completed the baseline and the follow-up surveys. As results of Hierarchical Linear Modeling, stairs/elevator (γ=3.80 [SE=1.80], p<0.05), physical activity/fitness facilities (γ=4.98 [SE=1.09], p<0.01), and written policies (γ=2.10 [SE=1.02], p<0.05) were significantly and positively associated with occupational physical activity. Self-regulation for physical activity was associated significantly with leisure-time physical activity (γ=0.09 [SE=0.04], p<0.05) but insignificantly with occupational and transport-related physical activity (γ=0.11 [SE=0.16] and γ=-0.00 [SE=0.06]). Significant interaction effects of workplace environments (physical activity/fitness facilities, work rules, and written policies) and self-regulation were observed on transport-related and leisure-time physical activity. Workplace environments such as physical activity/fitness facilities, written policies, work rules, and signs for stair use at stairs and elevators; self-regulation for physical activity; and their interactions may be effective to promote three domain-specific physical activities. This study has practical implications for designing multi-component interventions that include both environmental and psychological approaches to increase effect sizes to promote overall physical activity.

The Effect of Interruptions on Part 121 Air Carrier Operations

NASA Technical Reports Server (NTRS)

Damos, Diane L.

1998-01-01

The primary purpose of this study was to determine the relative priorities of various events and activities by examining the probability that a given activity was interrupted by a given event. The analysis will begin by providing frequency of interruption data by crew position (captain versus first officer) and event type. Any differences in the pattern of interruptions between the first officers and the captains will be explored and interpreted in terms of standard operating procedures. Subsequent data analyses will focus on comparing the frequency of interruptions for different types of activities and for the same activities under normal versus emergency conditions. Briefings and checklists will receive particular attention. The frequency with which specific activities are interrupted under multiple- versus single-task conditions also will be examined; because the majority of multiple-task data were obtained under laboratory conditions, LOFT-type tapes offer a unique opportunity to examine concurrent task performance under 'real-world' conditions. A second purpose of this study is to examine the effects of the interruptions on performance. More specifically, when possible, the time to resume specific activities will be compared to determine if pilots are slower to resume certain types of activities. Errors in resumption or failures to resume specific activities will be noted and any patterns in these errors will be identified. Again, particular attention will be given to the effects of interruptions on the completion of checklists and briefings. Other types of errors and missed events (i.e., the crew should have responded to the event but did not) will be examined. Any methodology using interruptions to examine task prioritization must be able to identify when an interruption has occurred and describe the ongoing activities that were interrupted. Both of these methodological problems are discussed In detail in the following section,

Verbal Short-Term Memory Deficits in Chinese Children with Dyslexia may not be a Problem with the Activation of Phonological Representations.

PubMed

Zhao, Jing; Yang, Yang; Song, Yao-Wu; Bi, Hong-Yan

2015-11-01

This study explored the underlying mechanism of the verbal short-term memory deficit in Chinese children with developmental dyslexia. Twenty-four children with dyslexia and 28 age-matched normal readers participated in the study. They were required to memorize a visually presented series of six Chinese characters and identify them from a list also including code-specific distracters and non-code-specific distracters. Error rates were recorded and were higher for code-specific distracters in all three conditions, revealing phonological, visual, and semantic similarity effects respectively. Group comparisons showed a stronger phonological similarity effect in dyslexic group, suggesting intact activation of phonological representations of target characters. Children with dyslexia also exhibited a greater semantic similarity effect, revealing stronger activation of semantic representations, while visual similarity effects were equivalent to controls. These results suggest that the verbal short-term memory deficit in Chinese dyslexics might not stem from insufficient activation of phonological information. Based the semantic activation of target characters in dyslexics is greater than in controls, it is possible that the memory deficit of dyslexia is related with deficient inhibition of target semantic representations in short-term memory. Copyright © 2015 John Wiley & Sons, Ltd.

Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents

NASA Astrophysics Data System (ADS)

Marassi, Valentina; Di Cristo, Luisana; Smith, Stephen G. J.; Ortelli, Simona; Blosi, Magda; Costa, Anna L.; Reschiglian, Pierluigi; Volkov, Yuri; Prina-Mello, Adriele

2018-01-01

Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a `purpose-specific active applicability window' to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response in vitro have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic Escherichia coli. The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety.

Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents.

PubMed

Marassi, Valentina; Di Cristo, Luisana; Smith, Stephen G J; Ortelli, Simona; Blosi, Magda; Costa, Anna L; Reschiglian, Pierluigi; Volkov, Yuri; Prina-Mello, Adriele

2018-01-01

Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a 'purpose-specific active applicability window' to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response in vitro have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic Escherichia coli . The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety.

Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents

PubMed Central

Marassi, Valentina; Di Cristo, Luisana; Smith, Stephen G. J.; Ortelli, Simona; Blosi, Magda; Costa, Anna L.; Reschiglian, Pierluigi; Volkov, Yuri

2018-01-01

Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a ‘purpose-specific active applicability window’ to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response in vitro have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic Escherichia coli. The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety. PMID:29410826

Pleiotropic Effects of Blastocystis spp. Subtypes 4 and 7 on Ligand-Specific Toll-Like Receptor Signaling and NF-κB Activation in a Human Monocyte Cell Line

PubMed Central

Teo, Joshua D. W.; MacAry, Paul A.; Tan, Kevin S. W.

2014-01-01

Blastocystis spp. is a common enteric stramenopile parasite that colonizes the colon of hosts of a diverse array of species, including humans. It has been shown to compromise intestinal epithelial cell barrier integrity and mediate the production of pro-inflammatory cytokines and chemokines. Mucosal epithelial surfaces, including the intestinal epithelium, are increasingly recognized to perform a vital surveillance role in the context of innate immunity, through the expression of pathogen recognition receptors, such as Toll-like receptors (TLRs). In this study, we use the human TLR reporter monocytic cell line, THP1-Blue, which expresses all human TLRs, to investigate effects of Blastocystis on TLR activation, more specifically the activation of TLR-2, -4 and -5. We have observed that live Blastocystis spp. parasites and whole cell lysate (WCL) alone do not activate TLRs in THP1-Blue. Live ST4-WR1 parasites inhibited LPS-mediated NF-κB activation in THP1-Blue. In contrast, ST7-B WCL and ST4-WR1 WCL induced pleiotropic modulation of ligand-specific TLR-2 and TLR-4 activation, with no significant effects on flagellin-mediated TLR-5 activation. Real time-qPCR analysis on SEAP reporter gene confirmed the augmenting effect of ST7-B on LPS-mediated NF-κB activation in THP1-Blue. Taken together, this is the first study to characterize interactions between Blastocystis spp. and host TLR activation using an in vitro reporter model. PMID:24551212

Automatic activation of alcohol cues by child maltreatment related words: a replication attempt in a different treatment setting.

PubMed

Potthast, Nadine; Neuner, Frank; Catani, Claudia

2017-01-03

A growing body of research attempts to clarify the underlying mechanisms of the association between emotional maltreatment and alcohol dependence (AD). In a preceding study, we found considerable support for a specific priming effect in subjects with AD and emotional abuse experiences receiving alcohol rehabilitation treatment. We concluded that maltreatment related cues can automatically activate an associative memory network comprising cues eliciting craving as well as alcohol-related responses. Generalizability of the results to other treatment settings remains unclear because of considerable differences in German treatment settings as well as insufficiently clarified influences of selection effects. As replication studies in other settings are necessary, the current study aimed to replicate the specific priming effect in a qualified detoxification sample. 22 AD subjects (n = 10 with emotional abuse vs. n = 12 without emotional abuse) participated in a priming experiment. Comparison data from 34 healthy control subjects were derived from the prior study. Contrary to our hypothesis, we did not find a specific priming effect. We could not replicate the result of an automatic network activation by maltreatment related words in a sample of subjects with AD and emotional abuse experiences receiving qualified detoxification treatment. This discrepancy might be attributed to reasons related to treatment settings as well as to methodological limitations. Future work is required to determine the generalizability of the specific priming effect before valid conclusions regarding automatic activation can be drawn.

Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

PubMed

Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

2018-04-02

Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells

PubMed Central

Suschek, Christoph; Kolb, Hubert; Kolb-Bachofen, Victoria

1997-01-01

Dobesilate is used for normalizing vascular dysfunction in a number of diseases. In search for an effect on endothelial NO production, macrovascular endothelial cells from rat aorta, microvascular endothelial cells from rat exocrine pancreatic tissue, and capillary endothelial cells from rat islets, were cultured in the presence or absence of Mg-Dobesilate. The activity of constitutive nitric oxide synthase (ecNOS) in resident cells as well as of inducible nitric oxide synthase (iNOS) in cytokine-activated cells was measured indirectly by recording the citrulline concentrations in culture supernatants.In each of the different endothelial cells Mg-Dobesilate incubation (0.25–1 mM) for 24 h led to a significant and concentration-dependent increase in ecNOS-activities. With cytokine-activated endothelial cell cultures only moderate effects were seen with little or no concentration-dependency. Addition of the NOS-inhibitor NG-monomethyl-L-arginine led to a significant suppression of citrulline formation in all cultures as an evidence for the enzyme specificity of these effects.iNOS- and ecNOS-specific reverse transcription and semi-quantitative polymerase chain reaction (RT–PCR) with RNA from resident or cytokine-activated endothelial cells gave no evidence for an increase in NOS-specific mRNA after Mg-Dobesilate-treatment. Furthermore, Dobesilate-mediated enhancement of NO synthesis in resting endothelial cells was not due to iNOS induction in these cells, as no iNOS-specific signal was found by RT–PCR. PMID:9421302

Deterrent activity of plant lectins on cowpea weevil Callosobruchus maculatus (F.) oviposition.

PubMed

Sadeghi, Amin; Van Damme, Els J M; Peumans, Willy J; Smagghe, Guy

2006-09-01

A set of 14 plant lectins was screened in a binary choice bioassay for inhibitory activity on cowpea weevil Callosobruchus maculatus (F.) oviposition. Coating of chickpea seeds (Cicer arietinum L.) with a 0.05% (w/v) solution of plant lectins caused a significant reduction in egg laying. Control experiments with heat inactivated lectin and BSA indicated that the observed deterrent effects are specific and require carbohydrate-binding activity. However, no clear correlation could be established between deterrent activity and sugar-binding specificity/molecular structure of the lectins. Increasing the insect density reduced the inhibitory effect of the lectins confirming that female insects are capable of adjusting their oviposition rates as a function of host availability.

Pathway-specific effect of caffeine on protection against UV irradiation-induced apoptosis in corneal epithelial cells.

PubMed

Wang, Ling; Lu, Luo

2007-02-01

To define the role of molecular interaction between the UV-induced JNK (c-Jun N-terminal kinase) cascade and corneal epithelial cell apoptosis and protection against apoptosis by caffeine. Rabbit and human corneal epithelial cells were cultured in DMEM/F12 medium containing 10% FBS and 5 microg/mL insulin at 37 degrees C in 5% CO(2). DNA fragmentation and ethidium bromide/acridine orange (EB/AO) nuclear staining were performed to detect cell death. Western blot, immunoprecipitation, and kinase assays were used to measure UV-induced mitogen-activated protein (MAP) kinase activity. UV irradiation-induced apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and MAKK4 (SEK1) upstream from JNK was caffeine sensitive. Caffeine (1,3,7-trimethylxanthine), an agent that is one of the most popular additions to food consumed in the world and a potential enhancer of chemotherapy, effectively protected corneal epithelial cells against apoptosis by its specific effect on the JNK cascade. Theophylline (1,3-dimethylxanthine) exhibited an effect similar to that of caffeine on prevention of UV irradiation-induced apoptosis. However, alterations of either intracellular cAMP or Ca(2+) levels did not alter the effect of caffeine on the JNK signaling pathway. In addition, the blockade of PI3K-like kinases by wortmannin had no impact on the protective effect of caffeine against UV irradiation-induced apoptosis, suggesting that the protective effect of caffeine acts through a specific mechanism involving UV irradiation-induced activation of ASK1 and SEK1. In contrast, caffeine had no effects on melphalan-, hyperosmotic stress-, or IL-1beta-induced activation of the JNK signaling pathway in these cells. UV irradiation stress-induced activation of the ASK1-SEK1-JNK signaling pathway leading to apoptosis is a caffeine-sensitive process, and caffeine, as a multifunctional agent in cells, can specifically interact with the pathway to protect against apoptosis.

Protective effects of buckwheat honey on DNA damage induced by hydroxyl radicals.

PubMed

Zhou, Juan; Li, Peng; Cheng, Ni; Gao, Hui; Wang, Bini; Wei, Yahui; Cao, Wei

2012-08-01

To understand the antioxidant properties of buckwheat honeys, we investigated their antioxidant effects on hydroxyl radical-induced DNA breaks in the non-site-specific and site-specific systems, the physicochemical properties, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity, chelating, and reducing power assays), total phenolic content and individual phenolic acids were also determined. Total phenolic content of buckwheat honeys ranged from 774 to 1694 mg PA/kg, and p-hydroxybenzoic and p-coumaric acids proved to be the main components in buckwheat honeys. All the buckwheat honey samples possess stronger capability to protect DNA in the non-site-specific systems than in the site-specific systems from being damaged by hydroxyl radicals. In the non-site-specific and site-specific system, buckwheat honeys samples prevented ()OH-induced DNA breaks by 21-78% and 5-31% over control value, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082

PubMed Central

Salling, Michael C.; Faccidomo, Sara; Hodge, Clyde W.

2008-01-01

Emerging evidence indicates that specific metabotropic glutamate receptors (mGluRs) modulate ethanol self-administration. In general, inhibition of glutamate transmission through blockade of postsynaptic mGluRs, or activation of presynaptic mGluRs, inhibits ethanol self-administration. The goal of this preclinical study was to further characterize mGluR regulation of ethanol self-administration by examining effects of AMN082, an allosteric positive modulator of presynaptic mGluR7 activity. Separate groups of C57BL/6J male mice were trained to self-administer ethanol or sucrose on a fixed-ratio 4 schedule of reinforcement during 1 hour sessions. On test days, mice were pretreated with AMN082 (0, 1.0, 3.0, 5.6, or 10 mg/kg) 30 minutes prior to self-administration sessions. Functional specificity and activity was examined by testing the effects of AMN082 (0 – 10 mg/kg) on open-field locomotor activity and HPA axis function as measured by plasma corticosterone levels. AMN082 (10 mg/kg) produced a significant reduction in ethanol and sucrose reinforced responding, and inhibited locomotor activity. Plasma corticosterone levels were significantly increased following AMN082 (5.6 and 10 mg/kg) suggesting a dose-dependent dissociation between the behavioral and hormonal effects of the compound. These data suggest that activation of mGluR7 by AMNO82 produces non-specific reductions in motivated behavior that are associated with negative effects on motor activity. PMID:18593591

Antigen-specific response of murine immune system toward a yeast beta-glucan preparation, zymosan.

PubMed

Miura, T; Ohno, N; Miura, N N; Adachi, Y; Shimada, S; Yadomae, T

1999-06-01

Zymosan, a particulate beta-glucan preparation from Saccharomyces cerevisiae, shows various biological activities, including anti-tumor activity. We have previously shown that soluble beta-glucan initiated anti-tumor activity was long-lived and was effective even by prophylactic treatment at 1 month prior to tumor challenge. However, the activity by zymosan was relatively short-lived. Antigen-specific responses of mice to zymosan might be a causative mechanism. In this paper, mice were immunized with zymosan and antibody production and antigen-specific responses of lymphocytes to zymosan were analyzed. Sera of zymosan immune mice contained zymosan-specific IgG assessed by enzyme-linked immunosorbent assay and FACS. Spleen and bone marrow cells of zymosan-immune mice showed higher cytokine production in response to zymosan. Specificity of zymosan-specific responses were also analyzed using various derivatives prepared from zymosan. These facts strongly suggested that mice recognize zymosan as antigen in addition to non-specific immune stimulant.

The Drosophila Circadian Clock Gates Sleep through Time-of-Day Dependent Modulation of Sleep-Promoting Neurons.

PubMed

Cavanaugh, Daniel J; Vigderman, Abigail S; Dean, Terry; Garbe, David S; Sehgal, Amita

2016-02-01

Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila. Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons. Sleep, as determined by activity monitoring and video tracking, was assessed before and after temperature-induced activation or inhibition using these effector molecules. We compared the effect of these manipulations in control flies and in mutant flies that lacked components of the molecular circadian clock. Adult-specific activation or inhibition of a population of neurons that projects to the sleep-promoting dorsal Fan-Shaped Body resulted in bidirectional control over sleep. Interestingly, the magnitude of the sleep changes were time-of-day dependent. Activation of sleep-promoting neurons was maximally effective during the middle of the day and night, and was relatively ineffective during the day-to-night and night-to-day transitions. These time-ofday specific effects were absent in flies that lacked functional circadian clocks. We conclude that the circadian system functions to gate sleep through active inhibition at specific times of day. These data identify a mechanism through which the circadian system prevents premature sleep onset in the late evening, when homeostatic sleep drive is high. © 2016 Associated Professional Sleep Societies, LLC.

A Systematic Review of the Effectiveness of Physical Education and School Sport Interventions Targeting Physical Activity, Movement Skills and Enjoyment of Physical Activity

ERIC Educational Resources Information Center

Dudley, Dean; Okely, Anthony; Pearson, Philip; Cotton, Wayne

2011-01-01

This article presents a systematic review of published literature on the effectiveness of physical education in promoting participation in physical activity, enjoyment of physical activity and movement skill proficiency in children and adolescents. The review utilized a literature search, specifically publications listed in Ovid, A+ Education,…

Associations between self-reported post-diagnosis physical activity changes, body weight changes, and psychosocial well-being in breast cancer survivors.

PubMed

Phillips, Siobhan M; McAuley, Edward

2015-01-01

Decreased physical activity and weight gain post-breast cancer diagnosis are associated with negative psychosocial, health, and disease outcomes, but little is known about how these factors interact. The purpose of the present study was to conduct a preliminary examination of the association between post-diagnosis physical activity changes, weight changes, and psychosocial well-being in breast cancer survivors. We examined the association between retrospectively collected, self-reported post-diagnosis changes in physical activity and body weight and post-diagnosis fatigue, anxiety, depression, stress, self-esteem, and health-related quality of life (HRQOL) in breast cancer survivors (N = 1,348) using univariate analyses of covariance with Bonferroni's adjustment. After adjusting for covariates, maintaining and/or increasing physical activity post-diagnosis was significantly (p < 0.05 for all), independently associated with lower fatigue, anxiety, depression and stress and higher physical self-worth, physical, social, emotional, functional and breast cancer specific well-being and overall HRQOL (effect sizes = 0.23 to 0.60). Maintaining and/or losing weight was significantly (p < 0.05), independently associated with lower fatigue and higher physical self-worth, physical and breast cancer-specific well-being, and overall HRQOL (effect sizes = .28 to 0.87). There were no significant interaction effects between physical activity and body weight changes. This study provides preliminary data to suggest that maintaining or increasing physical activity and controlling weight post-diagnosis may be independently, positively associated with psychosocial well-being and HRQOL in breast cancer survivors. In addition, weight management effects may be larger and more outcome-specific while physical activity effects may be more general. Future research is warranted to replicate and confirm these findings.

A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets

PubMed Central

Jia, Dongyu; Liu, Zhenqiu; Deng, Nan; Tan, Tuan Zea; Huang, Ruby Yun-Ju; Taylor-Harding, Barbie; Cheon, Dong-Joo; Lawrenson, Kate; Wiedemeyer, Wolf R.; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra

2016-01-01

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a ‘seed’, we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues. PMID:27609069

Can implicit appraisal concepts produce emotion-specific effects? A focus on unfairness and anger.

PubMed

Tong, Eddie M W; Tan, Deborah H; Tan, Yan Lin

2013-06-01

This research examined whether the non-conscious activation of an implicit appraisal concept could affect responses associated with the corresponding emotion as predicted by appraisal theories. Explicit and implicit emotional responses were examined. We focused on implicit unfairness and its effect on anger. The results show that subliminal activation of implicit unfairness affected implicit anger responses (anger facial expression and latency responses to anger words) but not explicit anger feelings (i.e., reported anger). The non-conscious effect of implicit unfairness was specific to anger, as no effect on sadness, fear, and guilt was found. Copyright © 2013 Elsevier Inc. All rights reserved.

TNFR2-deficient memory CD8 T cells provide superior protection against tumor cell growth.

PubMed

Kim, Edward Y; Teh, Soo-Jeet; Yang, Jocelyn; Chow, Michael T; Teh, Hung-Sia

2009-11-15

TNF receptor-2 (TNFR2) plays a critical role in promoting the activation and survival of naive T cells during the primary response. Interestingly, anti-CD3 plus IL-2 activated TNFR2(-/-) CD8 T cells are highly resistant to activation-induced cell death (AICD), which correlates with high expression levels of prosurvival molecules such as Bcl-2, survivin, and CD127 (IL-7Ralpha). We determined whether the resistance of activated TNFR2(-/-) CD8 T cells to AICD contributes to more effective protection against tumor cell growth. We found that during a primary tumor challenge, despite initial inferiority in controlling tumor cell growth, TNFR2(-/-) mice were able to more effectively control tumor burden over time compared with wild-type (WT) mice. Furthermore, vaccination of TNFR2(-/-) mice with recombinant Listeria monocytogenes that express OVA confers better protection against the growth of OVA-expressing E.G7 tumor cells relative to similarly vaccinated WT mice. The enhanced protection against tumor cell growth was not due to more effective activation of OVA-specific memory CD8 T cells in vaccinated TNFR2(-/-) mice. In vitro studies indicate that optimally activated OVA-specific TNFR2(-/-) CD8 T cells proliferated to the same extent and possess similar cytotoxicity against E.G7 tumor cells as WT CD8 T cells. However, relative to WT cells, activated OVA-specific TNFR2(-/-) CD8 T cells were highly resistant to AICD. Thus, the enhanced protection against E.G7 in TNFR2(-/-) mice is likely due to the recruitment and activation of OVA-specific memory TNFR2(-/-) CD8 T cells and their prolonged survival at the tumor site.

Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.

PubMed

Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L; Blazer, Vicki S; Halpern, Marnie E

2014-04-01

Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

USGS Publications Warehouse

Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

2014-01-01

Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

[The effect of nitrofurans on the membrane apparatus of coccal bacteria].

PubMed

Kutsmako, R T; Kuliash, Iu V; Rudzit, E A; Ermachenko, V A; Simakova, I M

1984-01-01

Secondary membrane effects on the membrane apparatus of coccus bacteria were being studied. Cultivation of Micrococcus lysodeikticus and Staphylococcus aureus cells on subbacteriostatic concentrations of nitrofurans results in a lower biosynthesis of many membrane proteins, as well as in inhibiting the activity of respiratory enzymes, i. e. the specific concentration of cytochromes and specific activity of NADH-, malate-, lactate oxidases and some reductases drop. Some cytological changes were revealed, when cells were grown on solafur, furazolidone, and furacriline.

Stimulation, Inhibition, or Stabilization of Na,K-ATPase Caused by Specific Lipid Interactions at Distinct Sites

PubMed Central

Habeck, Michael; Haviv, Haim; Katz, Adriana; Kapri-Pardes, Einat; Ayciriex, Sophie; Shevchenko, Andrej; Ogawa, Haruo; Toyoshima, Chikashi; Karlish, Steven J. D.

2015-01-01

The activity of membrane proteins such as Na,K-ATPase depends strongly on the surrounding lipid environment. Interactions can be annular, depending on the physical properties of the membrane, or specific with lipids bound in pockets between transmembrane domains. This paper describes three specific lipid-protein interactions using purified recombinant Na,K-ATPase. (a) Thermal stability of the Na,K-ATPase depends crucially on a specific interaction with 18:0/18:1 phosphatidylserine (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-l-serine; SOPS) and cholesterol, which strongly amplifies stabilization. We show here that cholesterol associates with SOPS, FXYD1, and the α subunit between trans-membrane segments αTM8 and -10 to stabilize the protein. (b) Polyunsaturated neutral lipids stimulate Na,K-ATPase turnover by >60%. A screen of the lipid specificity showed that 18:0/20:4 and 18:0/22:6 phosphatidylethanolamine (PE) are the optimal phospholipids for this effect. (c) Saturated phosphatidylcholine and sphingomyelin, but not saturated phosphatidylserine or PE, inhibit Na,K-ATPase activity by 70–80%. This effect depends strongly on the presence of cholesterol. Analysis of the Na,K-ATPase activity and E1-E2 conformational transitions reveals the kinetic mechanisms of these effects. Both stimulatory and inhibitory lipids poise the conformational equilibrium toward E2, but their detailed mechanisms of action are different. PE accelerates the rate of E1 → E2P but does not affect E2(2K)ATP → E13NaATP, whereas sphingomyelin inhibits the rate of E2(2K)ATP → E13NaATP, with very little effect on E1 → E2P. We discuss these lipid effects in relation to recent crystal structures of Na,K-ATPase and propose that there are three separate sites for the specific lipid interactions, with potential physiological roles to regulate activity and stability of the pump. PMID:25533463

Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure.

PubMed

Bao, Haibo; Shao, Xusheng; Zhang, Yixi; Deng, Yayun; Xu, Xiaoyong; Liu, Zewen; Li, Zhong

2016-06-29

Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid-specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products.

Insight into the role of substrate-binding residues in conferring substrate specificity for the multifunctional polysaccharide lyase Smlt1473.

PubMed

MacDonald, Logan C; Berger, Bryan W

2014-06-27

Anionic polysaccharides are of growing interest in the biotechnology industry due to their potential pharmaceutical applications in drug delivery and wound treatment. Chemical composition and polymer length strongly influence the physical and biological properties of the polysaccharide and thus its potential industrial and medical applications. One promising approach to determining monomer composition and controlling the degree of polymerization involves the use of polysaccharide lyases, which catalyze the depolymerization of anionic polysaccharides via a β-elimination mechanism. Utilization of these enzymes for the production of custom-made oligosaccharides requires a high degree of control over substrate specificity. Previously, we characterized a polysaccharide lyase (Smlt1473) from Stenotrophomonas maltophilia k279a, which exhibited significant activity against hyaluronan (HA), poly-β-d-glucuronic acid (poly-GlcUA), and poly-β-d-mannuronic acid (poly-ManA) in a pH-regulated manner. Here, we utilize a sequence structure guided approach based on a homology model of Smlt1473 to identify nine putative substrate-binding residues and examine their effect on substrate specificity via site-directed mutagenesis. Interestingly, single point mutations H221F and R312L resulted in increased activity and specificity toward poly-ManA and poly-GlcUA, respectively. Furthermore, a W171A mutant nearly eliminated HA activity, while increasing poly-ManA and poly-GlcUA activity by at least 35%. The effect of these mutations was analyzed by comparison with the high resolution structure of Sphingomonas sp. A1-III alginate lyase in complex with poly-ManA tetrasaccharide and by taking into account the structural differences between HA, poly-GlcUA, and poly-ManA. Overall, our results demonstrate that even minor changes in active site architecture have a significant effect on the substrate specificity of Smlt1473, whose structural plasticity could be applied to the design of highly active and specific polysaccharide lyases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential involvement of cortical and cerebellar areas using dominant and nondominant hands: An FMRI study

PubMed Central

Pardini, Matteo; Samson, Rebecca S.; D'Angelo, Egidio; Friston, Karl J.; Toosy, Ahmed T.; Gandini Wheeler‐Kingshott, Claudia A.M.

2015-01-01

Abstract Motor fMRI studies, comparing dominant (DH) and nondominant (NDH) hand activations have reported mixed findings, especially for the extent of ipsilateral (IL) activations and their relationship with task complexity. To date, no study has directly compared DH and NDH activations using an event‐related visually guided dynamic power‐grip paradigm with parametric (three) forces (GF) in healthy right‐handed subjects. We implemented a hierarchical statistical approach aimed to: (i) identify the main effect networks engaged when using either hand; (ii) characterise DH/NDH responses at different GFs; (iii) assess contralateral (CL)/IL‐specific and hemisphere‐specific activations. Beyond confirming previously reported results, this study demonstrated that increasing GF has an effect on motor response that is contextualised also by the use of DH or NDH. Linear analysis revealed increased activations in sensorimotor areas, with additional increased recruitments of subcortical and cerebellar areas when using the NDH. When looking at CL/IL‐specific activations, CL sensorimotor areas and IL cerebellum were activated with both hands. When performing the task with the NDH, several areas were also recruited including the CL cerebellum. Finally, there were hand‐side‐independent activations of nonmotor‐specific areas in the right and left hemispheres, with the right hemisphere being involved more extensively in sensori‐motor integration through associative areas while the left hemisphere showing greater activation at higher GF. This study shows that the functional networks subtending DH/NDH power‐grip visuomotor functions are qualitatively and quantitatively distinct and this should be taken into consideration when performing fMRI studies, particularly when planning interventions in patients with specific impairments. Hum Brain Mapp 36:5079–5100, 2015. © 2015 Wiley Periodicals, Inc. PMID:26415818

Psychosocial determinants of out of school activity participation for children with and without physical disabilities.

PubMed

King, Gillian; Law, Mary; Petrenchik, Theresa; Hurley, Patricia

2013-11-01

Psychosocial determinants of children's out of school participation were examined, using secondary analyses of data from 427 children with physical disabilities (from 12 service locations in Ontario Canada) and 354 children without disabilities, ages 6 to 14. For both groups of children, hierarchical regression analyses indicated that psychosocial variables added significant incremental variance (6% to 14%) to the prediction of active physical intensity and social activity enjoyment, beyond that accounted for by family income, child age and sex, and physical functioning. As well, there were significant psychosocial determinants, with medium to large effect sizes. Athletic competence and hyperactivity had specific effects on active physical activities and social activities, respectively, for both groups of children. Disability-specific determinants included social acceptance, emotional functioning, and peer difficulties (only significant for children with disabilities). It was concluded that psychosocial variables play an important role in children's enjoyment and intensity of participation in leisure activities.

Sedentary behavior and residual-specific mortality

PubMed Central

Loprinzi, Paul D.; Edwards, Meghan K.; Sng, Eveleen; Addoh, Ovuokerie

2016-01-01

Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0.05). There was evidence of an interaction effect between sedentary behavior and total physical activity on residual-specific mortality (Hazard ratiointeraction [HR] = 0.9989; 95% CI: 0.9982-0.9997; P = 0.008). Conclusion: Sedentary behavior was independently associated with residual-specific mortality. However, there was evidence to suggest that residual-specific mortality risk was a function of sedentary behavior and total physical activity. These findings highlight the need for future work to not only examine the association between sedentary behavior and health independent of total physical activity, but evaluate whether there is a joint effect of these two parameters on health. PMID:27766237

Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response.

PubMed

Tiemessen, Machteld M; Kunzmann, Steffen; Schmidt-Weber, Carsten B; Garssen, Johan; Bruijnzeel-Koomen, Carla A F M; Knol, Edward F; van Hoffen, Els

2003-12-01

Transforming growth factor (TGF)-beta has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-beta on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-beta is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-beta resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-beta is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-beta. Although TGF-beta was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This could not be correlated to differential expression of TGF-beta signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-beta has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.

The effects of activating prior topic and metacognitive knowledge on text comprehension scores.

PubMed

Kostons, Danny; van der Werf, Greetje

2015-09-01

Research on prior knowledge activation has consistently shown that activating learners' prior knowledge has beneficial effects on learning. If learners activate their prior knowledge, this activated knowledge serves as a framework for establishing relationships between the knowledge they already possess and new information provided to them. Thus far, prior knowledge activation has dealt primarily with topic knowledge in specific domains. Students, however, likely also possess at least some metacognitive knowledge useful in those domains, which, when activated, should aid in the deployment of helpful strategies during reading. In this study, we investigated the effects of both prior topic knowledge activation (PTKA) and prior metacognitive knowledge activation (PMKA) on text comprehension scores. Eighty-eight students in primary education were randomly distributed amongst the conditions of the 2 × 2 (PTKA yes/no × PMKA yes/no) designed experiment. Results show that activating prior metacognitive knowledge had a beneficial effect on text comprehension, whereas activating prior topic knowledge, after correcting for the amount of prior knowledge, did not. Most studies deal with explicit instruction of metacognitive knowledge, but our results show that this may not be necessary, specifically in the case of students who already have some metacognitive knowledge. However, existing metacognitive knowledge needs to be activated in order for students to make better use of this knowledge. © 2015 The British Psychological Society.

A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface.

PubMed

Warfield, Linda; Tuttle, Lisa M; Pacheco, Derek; Klevit, Rachel E; Hahn, Steven

2014-08-26

Although many transcription activators contact the same set of coactivator complexes, the mechanism and specificity of these interactions have been unclear. For example, do intrinsically disordered transcription activation domains (ADs) use sequence-specific motifs, or do ADs of seemingly different sequence have common properties that encode activation function? We find that the central activation domain (cAD) of the yeast activator Gcn4 functions through a short, conserved sequence-specific motif. Optimizing the residues surrounding this short motif by inserting additional hydrophobic residues creates very powerful ADs that bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein interface. In contrast to Gcn4, the activity of these synthetic ADs is not strongly dependent on any one residue of the AD, and this redundancy is similar to that of some natural ADs in which few if any sequence-specific residues have been identified. The additional hydrophobic residues in the synthetic ADs likely allow multiple faces of the AD helix to interact with the Gal11 activator-binding domain, effectively forming a fuzzier interface than that of the wild-type cAD.

PPARbeta/delta agonists modulate platelet function via a mechanism involving PPAR receptors and specific association/repression of PKCalpha--brief report.

PubMed

Ali, Ferhana Y; Hall, Matthew G; Desvergne, Béatrice; Warner, Timothy D; Mitchell, Jane A

2009-11-01

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is a nuclear receptor found in platelets. PPARbeta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPARbeta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPARbeta/delta receptors and their intracellular signaling pathways in platelets are not known. We have used mice lacking PPARbeta/delta (PPARbeta/delta(-/-)) to show the effects of the PPARbeta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPARbeta/delta, however GW501516 had no PPARbeta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKCalpha, which can mediate platelet activation, was bound and repressed by PPARbeta/delta after platelets were treated with GW501516. These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk.

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

PubMed

Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

2009-09-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

Effects of Neonicotinoid Pesticides on Promoter-Specific Aromatase (CYP19) Expression in Hs578t Breast Cancer Cells and the Role of the VEGF Pathway.

PubMed

Caron-Beaudoin, Élyse; Viau, Rachel; Sanderson, J Thomas

2018-04-26

Aromatase (CYP19) is a key enzyme in estrogens biosynthesis. In the mammary gland, CYP19 gene is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, fibroblast cells surrounding the tumor express increased levels of CYP19 mRNA due to a decrease of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter activity. Little is known about the effects of environmental chemicals on the promoter-specific CYP19 expression. We aimed to determine the effects of two neonicotinoids (thiacloprid and imidacloprid) on promoter-specific CYP19 expression in Hs578t breast cancer cells and understand the signaling pathways involved. Hs578t cells were exposed to various signaling pathway stimulants or neonicotinoids for 24 h. Promoter-specific expression of CYP19 was determined by real-time quantitative polymerase chain reaction and catalytic activity of aromatase by tritiated water release assay. To our knowledge, we are the first to demonstrate that the normal I.4 promoter and the breast cancer-relevant PII, I.3, and I.7 promoters of CYP19 are active in these cells. We found that the expression of CYP19 via promoters PII, I.3, and I.7 in Hs578t cells was, in part, dependent on the activation of two VEGF signaling pathways: mitogen-activated protein kinase (MAPK) 1/3 and phospholipase C (PLC). Exposure of Hs578t cells to environmental concentrations of imidacloprid and thiacloprid resulted in a switch in CYP19 promoter usage, involving inhibition of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter-mediated CYP19 expression and aromatase catalytic activity. Greater effects were seen at lower concentrations. Our results suggest that thiacloprid and imidacloprid exert their effects at least partially by inducing the MAPK 1/3 and/or PLC pathways. We demonstrated in vitro that neonicotinoids may stimulate a change in CYP19 promoter usage similar to that observed in patients with hormone-dependent breast cancer. https://doi.org/10.1289/EHP2698.

GW501516 acts as an efficient PPARα activator in the mouse liver.

PubMed

Terada, M; Araki, M; Ashibe, B; Motojima, K

2011-08-01

The peroxisome proliferator-activated receptor (PPAR) subtype specificity of GW501516, a well-known PPARδ-specific agonist, was studied by examining its effects on the expression of endogenous genes in primary hepatocytes and the liver of wild-type and PPARα-null mice. GW501516, like the PPARα-specific agonist Wy14,643, induced the expression of several PPAR target genes in a dose-dependent manner but this action was mostly absent in the cells and liver of PPARα-null mice. Results indicated that GW501516 acts as an efficient PPARα activator in the mouse liver.

Mechanism-specific effects of adenosine on ventricular tachycardia.

PubMed

Lerman, Bruce B; Ip, James E; Shah, Bindi K; Thomas, George; Liu, Christopher F; Ciaccio, Edward J; Wit, Andrew L; Cheung, Jim W; Markowitz, Steven M

2014-12-01

There is no universally accepted method by which to diagnose clinical ventricular tachycardia (VT) due to cAMP-mediated triggered activity. Based on cellular and clinical data, adenosine termination of VT is thought to be consistent with a diagnosis of triggered activity. However, a major gap in evidence mitigates the validity of this proposal, namely, defining the specificity of adenosine response in well-delineated reentrant VT circuits. To this end, we systematically studied the effects of adenosine in a model of canine reentrant VT and in human reentrant VT, confirmed by 3-dimensional, pace- and substrate mapping. Adenosine (12 mg [IQR 12-24]) failed to terminate VT in 31 of 31 patients with reentrant VT due to structural heart disease, and had no effect on VT cycle length (age, 67 years [IQR 53-74]); ejection fraction, 35% [IQR 20-55]). In contrast, adenosine terminated VT in 45 of 50 (90%) patients with sustained focal right or left outflow tract tachycardia. The sensitivity of adenosine for identifying VT due to triggered activity was 90% (95% CI, 0.78-0.97) and its specificity was 100% (95% CI, 0.89-1.0). Additionally, reentrant circuits were mapped in the epicardial border zone of 4-day-old infarcts in mongrel dogs. Adenosine (300-400 μg/kg) did not terminate sustained VT or have any effect on VT cycle length. These data support the concept that adenosine's effects on ventricular myocardium are mechanism specific, such that termination of VT in response to adenosine is diagnostic of cAMP-mediated triggered activity. © 2014 Wiley Periodicals, Inc.

Optimisation of sewage sludge anaerobic digestion through co-digestion with OFMSW: Effect of collection system and particle size

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

Silvestre, Gracia; Ainia, Departamento de Medio Ambiente, Bioenergía e Higiene Industrial, Paterna, Valencia; Bonmatí, August

2015-09-15

Highlights: • Methane production rate increased between 56% and 208% during OFMSW–SS codigestion. • The OFMSW particle size reduction from 20 to 8 mm did not affect the methane yield. • OFMSW–SS codigestion promoted β-oxidation and acetoclastic methanogenic activity. • The evolution of specific activity was a feasible tool to control the process. - Abstract: The effect of organic fraction of municipal solid waste (OFMSW) loading rate and particulate size on the sewage sludge (SS) mesophilic anaerobic co-digestion was assessed in continuous stirred tank reactor at hydraulic retention time of 20 days. The SS–OFMSW mixture composed by 54% of themore » volatile solids fed (inlet-VS), at OLR of 3.1 kg{sub COD} m{sup −3} d{sup −1} (1.9 kg{sub VS} m{sup −3} d{sup −1}), showed the highest increment on the volumetric methane production and yield of +200% and +59% respectively, under stable conditions. The effect of particulate size was assessed with the same mixture and same operational conditions but reducing the OFMSW particulate size from 20 mm to 8 mm with the aim to improve the hydrolysis step, but the results showed any influence in the OFMSW particulate size range analysed. In addition, specific biomass activity was assessed at the end of each co-digestion period. Results showed that OFMSW promoted β-oxidation syntrophic acetogens and the acetoclastic methanogens activity; although the last increase of the OFMSW percentage (from 47% to 54% inlet-VS) affected negatively the specific substrate activity, but not inhibitory effect was observed. Therefore, the results obtained in the continuous experiment could be related with some inhibitory or toxic effect and not due to hydrolysis limitation. The specific biomass activity test was demonstrated to be an interesting tool to evaluate and control the co-digestion process, especially when conventional parameters did not explain the behaviour of the biological system.« less

Physical activity, sedentary behaviour and sleep in COPD guidelines: A systematic review.

PubMed

Lewthwaite, Hayley; Effing, Tanja W; Olds, Timothy; Williams, Marie T

2017-08-01

Physical activity, sedentary and sleep behaviours have strong associations with health. This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours. A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005. Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim. The proportions of CPGs providing specific recommendations and strategies were reported. From 2370 citations identified, 35 CPGs were eligible for inclusion. Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep. The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4). Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs.

The role of obesity and physical activity in non-specific and radiating low back pain: the Young Finns study.

PubMed

Shiri, Rahman; Solovieva, Svetlana; Husgafvel-Pursiainen, Kirsti; Telama, Risto; Yang, Xiaolin; Viikari, Jorma; Raitakari, Olli T; Viikari-Juntura, Eira

2013-06-01

To study the effects of obesity, physical activity, and change in physical activity on the incidence of low back pain and explore whether obesity modifies the effects of physical activity. As part of the ongoing Young Finns Study, 1224 subjects aged 24-39 years free from low back pain during the preceding 12 months at baseline in 2001 were included. Obesity was defined based on the body mass index (BMI) and waist circumference, and physical activity was assessed by the metabolic equivalent of task (MET) index in 2001 and 2007. Abdominal obesity, defined by an increased waist circumference, was associated with an increased incidence of radiating low back pain (adjusted odds ratio (OR) = 1.7 and 95% confidence interval (CI) 1.1-2.7), while it had no effect on non-specific low back pain. BMI was associated neither with the incidence of radiating low back pain nor with non-specific low back pain. Compared with subjects who stayed active during follow-up, those with a low level of physical activity (adjusted OR = 2.0 and 95% CI 1.1-3.5) and active subjects who further increased their physical activity during follow-up (OR = 3.1 and 95% CI 1.5-6.7) had a higher incidence of radiating low back pain. Low level of physical activity was associated with an increased incidence of radiating low back pain in obese (OR = 3.3 and 95% 1.1-10.4), but not in non-overweight subjects (OR = 1.1 and 95% CI 0.6-1.9). Physical activity was not associated with non-specific low back pain. Our findings indicate that both obesity and low level of physical activity are independent risk factors of radiating low back pain. The current findings propose a U-shaped relation between physical activity and radiating low back pain. Moderate level of physical activity is recommended for the prevention of low back pain, especially in obese individuals. In all, our findings imply that obese individuals should stay physically active, even if they may not lose weight. Copyright © 2013 Elsevier Inc. All rights reserved.

Mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes, which induces biological effects.

PubMed

Jeyaseelan, S; Kannan, M S; Briggs, R E; Thumbikat, P; Maheswaran, S K

2001-10-01

The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces biological effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any effects. These findings suggest that the specificity of LktA effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to biological effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for biological effects. We used a biologically inactive mutant leukotoxin (DeltaLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The DeltaLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced biological effects.

Mannheimia haemolytica Leukotoxin Activates a Nonreceptor Tyrosine Kinase Signaling Cascade in Bovine Leukocytes, Which Induces Biological Effects

PubMed Central

Jeyaseelan, S.; Kannan, M. S.; Briggs, R. E.; Thumbikat, P.; Maheswaran, S. K.

2001-01-01

The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces biological effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any effects. These findings suggest that the specificity of LktA effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to biological effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for biological effects. We used a biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced biological effects. PMID:11553552

Vernier perceptual learning transfers to completely untrained retinal locations after double training: A “piggybacking” effect

PubMed Central

Wang, Rui; Zhang, Jun-Yun; Klein, Stanley A.; Levi, Dennis M.; Yu, Cong

2014-01-01

Perceptual learning, a process in which training improves visual discrimination, is often specific to the trained retinal location, and this location specificity is frequently regarded as an indication of neural plasticity in the retinotopic visual cortex. However, our previous studies have shown that “double training” enables location-specific perceptual learning, such as Vernier learning, to completely transfer to a new location where an irrelevant task is practiced. Here we show that Vernier learning can be actuated by less location-specific orientation or motion-direction learning to transfer to completely untrained retinal locations. This “piggybacking” effect occurs even if both tasks are trained at the same retinal location. However, piggybacking does not occur when the Vernier task is paired with a more location-specific contrast-discrimination task. This previously unknown complexity challenges the current understanding of perceptual learning and its specificity/transfer. Orientation and motion-direction learning, but not contrast and Vernier learning, appears to activate a global process that allows learning transfer to untrained locations. Moreover, when paired with orientation or motion-direction learning, Vernier learning may be “piggybacked” by the activated global process to transfer to other untrained retinal locations. How this task-specific global activation process is achieved is as yet unknown. PMID:25398974

75 FR 39952 - Agency Information Collection Activities; Proposed Collection; Comment Request; Testing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... audiences that FDA needs to design effective communication strategies, messages, and labels. These... group settings. Third, as evaluative research, it will allow FDA to ascertain the effectiveness of the... include contractor expenses for designing and conducting information collection activities, specifically...

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

EPA Science Inventory

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metric...

Beyond AICA Riboside: In Search of New Specific AMP-activated Protein Kinase Activators

PubMed Central

Guigas, Bruno; Sakamoto, Kei; Taleux, Nellie; Reyna, Sara M.; Musi, Nicolas; Viollet, Benoit; Hue, Louis

2010-01-01

Summary 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to activate the AMP-activated protein kinase (AMPK), a metabolic sensor involved in both cellular and whole body energy homeostasis. However, it has been recently highlighted that AICA riboside also exerts AMPK-independent effects, mainly on AMP-regulated enzymes and mitochondrial oxidative phosphorylation (OXPHOS), leading to the conclusion that new compounds with reduced off target effects are needed to specifically activate AMPK. Here, we review recent findings on newly discovered AMPK activators, notably on A-769662, a nonnucleoside compound from the thienopyridone family. We also report that A-769662 is able to activate AMPK and stimulate glucose uptake in both L6 cells and primary myotubes derived from human satellite cells. In addition, A-769662 increases AMPK activity and phosphorylation of its main downstream targets in primary cultured rat hepatocytes but, by contrast with AICA riboside, does neither affect mitochondrial OXPHOS nor change cellular AMP:ATP ratio. We conclude that A-769662 could be one of the new promising chemical agents to activate AMPK with limited AMPK-independent side effects. PMID:18798311

Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia.

PubMed

Chen, Yan; Chen, Hongmei; Birnbaum, Yochai; Nanhwan, Manjyot K; Bajaj, Mandeep; Ye, Yumei; Qian, Jinqiao

2017-03-01

To assess the effects of Aleglitazar on hyperglycaemia-induced apoptosis. We incubated human cardiomyocytes, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout or wild-type mice in normoglycaemic or hyperglycaemic conditions (glucose 25 mM). Cells were treated with different concentrations of Aleglitazar for 48 h. We measured viability, apoptosis, caspase-3 activity, cytochrome-C release, total antioxidant capacity and reactive oxygen species formation in the treated cardiomyocytes. Human cardiomyocytes were transfected with short interfering RNA against peroxisome proliferator-activated receptor-α or peroxisome proliferator-activated receptor-γ. Aleglitazar attenuated hyperglycaemia-induced apoptosis, caspase-3 activity and cytochrome-C release and increased viability in human cardiomyocyte, cardiomyocytes from cardiac-specific peroxisome proliferator-activated receptor-γ knockout and wild-type mice. Hyperglycaemia reduced the antioxidant capacity and Aleglitazar significantly blunted this effect. Hyperglycaemia-induced reactive oxygen species production was attenuated by Aleglitazar in both human cardiomyocyte and wild-type mice cardiomyocytes. Aleglitazar improved cell viability in cells exposed to hyperglycaemia. The protective effect was partially blocked by short interfering RNA against peroxisome proliferator-activated receptor-α alone and short interfering RNA against peroxisome proliferator-activated receptor-γ alone and completely blocked by short interfering RNA to both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ. Aleglitazar protects cardiomyocytes against hyperglycaemia-induced apoptosis by combined activation of both peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in a short-term vitro model.

Effect of feeding and of DDT on the activity of hepatic glucose 6- phosphate dehydrogenase in two salmonids

USGS Publications Warehouse

Buhler, Donald R.; Benville, P.

1969-01-01

The specific activity of liver glucose 6-phosphate dehydrogenase in yearling rainbow trout remained unchanged when the fish were starved for periods as long as 8 weeks and when starved animals were fed diets of various compositions. Injection of insulin concurrently with refeeding also failed to alter the specific activity of the enzyme in trout. The absence of a dietary or insulin influence on the teleost enzyme system is to be contrasted with studies in mammals in which the activity of hepatic glucose 6-P dehydrogenase was markedly stimulated after refeeding starved animals or injection of insulin.Ingestion of the pesticide DDT by juvenile coho salmon or adult rainbow trout also had no effect on the specific activity of liver glucose 6-P dehydrogenase and DDT failed to inhibit the rainbow trout enzyme in vitro. These results also differ considerably from those found in higher animals.These results suggest that the glucose 6-P dehydrogenase enzyme in teleosts may be under a different type of regulatory control from that found in mammals.

Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

PubMed Central

Valentini, Elia; Koch, Katharina; Aglioti, Salvatore Maria

2014-01-01

Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations. PMID:25386905

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

Specific or nonspecific? Evaluation of band, baseline, and cognitive specificity of sensorimotor rhythm- and gamma-based neurofeedback.

PubMed

Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme

2017-10-01

Neurofeedback (NF) is often criticized because of the lack of empirical evidence of its specificity. Our present study thus focused on the specificity of NF on three levels: band specificity, cognitive specificity, and baseline specificity. Ten healthy middle-aged individuals performed ten sessions of SMR (sensorimotor rhythm, 12-15Hz) NF training. A second group (N=10) received feedback of a narrow gamma band (40-43Hz). Effects of NF on EEG resting measurements (tonic EEG) and cognitive functions (memory, intelligence) were evaluated using a pre-post design. Both training groups were able to linearly increase the target training frequencies (either SMR or gamma), indicating the trainability of these EEG frequencies. Both NF training protocols led to nonspecific changes in other frequency bands during NF training. While SMR NF only led to concomitant changes in slower frequencies, gamma training affected nearly the whole power spectrum. SMR NF specifically improved memory functions. Gamma training showed only marginal effects on cognitive functions. SMR power assessed during resting measurements significantly increased after SMR NF training compared to a pre-assessment, indicating specific effects of SMR NF on baseline/tonic EEG. The gamma group did not show any pre-post changes in their EEG resting activity. In conclusion, SMR NF specifically affects cognitive functions (cognitive specificity) and tonic EEG (baseline specificity), while increasing SMR during NF training nonspecifically affects slower EEG frequencies as well (band non-specificity). Gamma NF was associated with nonspecific effects on the EEG power spectrum during training, which did not lead to considerable changes in cognitive functions or baseline EEG activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

PubMed

Hu, Ming; Zhao, Jixian; Ai, Xiangzhao; Budanovic, Maja; Mu, Jing; Webster, Richard D; Cao, Qian; Mao, Zongwan; Xing, Bengang

2016-09-13

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

A sensitive electrochemical biosensor for detection of protein kinase A activity and inhibitors based on Phos-tag and enzymatic signal amplification.

PubMed

Yin, Huanshun; Wang, Mo; Li, Bingchen; Yang, Zhiqing; Zhou, Yunlei; Ai, Shiyun

2015-01-15

A simple, highly sensitive and selective electrochemical assay is developed for the detection of protein kinase A (PKA) activity based on the specific recognition utility of Phos-tag for kinase-induced phosphopeptides and enzymatic signal amplification. When the substrate peptide was phosphorylated by PKA reaction, they could specifically bind with Phos-tag-biotin in the presence of Zn(2+) through the formation of a specific noncovalent complex with the phosphomonoester dianion in phosphorylated peptides. Through the further specific interaction between biotin and avidin, avidin functionalized horseradish peroxidase (HRP) can be captured on the electrode surface. Under the catalytic effect of HRP, a sensitive electrochemical signal for benzoquinone was obtained, which was related to PKA activity. Under the optimal experiment conditions, the proposed electrochemical method presented dynamic range from 0.5 to 25 unit/mL with low detection limit of 0.15 unit/mL. This new detection strategy was also successfully applied to analyze the inhibition effect of inhibitors (ellagic acid and H-89) on PKA activity and monitored the PKA activity in cell lysates. Therefore, this Phos-tag-based electrochemical assay offers an alternative platform for PKA activity assay and inhibitor screening, and thus it might be a valuable tool for development of targeted therapy and clinical diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Prescribed burning effects on soil enzyme activity in a southern Ohio hardwood forest: A landscape-scale analysis

Treesearch

Ralph E. J. Boerner; Kelly L. M. Decker; Elaine K. Sutherland

2000-01-01

We assessed the effect of a single, dormant season prescribed fire on soil enzyme activity in oak-hickory (Quercus-Carya) forests in southern Ohio, USA. Four enzymes specific for different C sources were chosen for monitoring: acid phosphatase, beta-glucosidase, chitinase and phenol oxidase. Postfire acid phosphatase activity was generally reduced by burning and...

Factors Influencing the Effects of Parental Marital Status on Adolescent Sexual Activity.

ERIC Educational Resources Information Center

Renninger, Gretchen; Chambliss, Catherine

Many studies have been done pertaining to the effects of parental divorce on children. Recently, studies have shown that parental marital status has an effect on adolescents' sexual activity. Specifically, children of divorced parents have been found to be younger at first coitus than children of married parents. This study attempted to replicate…

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural effect of quaternary ammonium chitin derivatives on their bactericidal activity and specificity.

PubMed

Morkaew, Tirut; Pinyakong, Onruthai; Tachaboonyakiat, Wanpen

2017-08-01

The effect of the quaternary ammonium chitin structure on the bactericidal activity and specificity against Escherichia coli and Staphylococcus aureus was investigated. Quaternary ammonium chitins were synthesized by the separate acylation of chitin (CT) with carboxymethyl trimethylammonium chloride (CMA), 3-carboxypropyl trimethylammonium chloride (CPA) and N-dodecyl-N,N-(dimethylammonio)butyrate (DDMAB). The successful acylation was confirmed by newly formed ester linkage. All three derivatives had a higher surface charge than chitin due to the additional positively charged quaternary ammonium groups. The N-short alkyl substituent (methyl) of CTCMA and CTCPA increased the hydrophilicity whilst the N-long alkyl substituent (dodecyl) of CTDDMAB increased the hydrophobicity compared to chitin. Chitin did not exhibit any bactericidal activity, while CTCMA and CTCPA completely killed E. coli and S. aureus in 30 and 60min, respectively, and CTDDMAB completely killed S. aureus in 10min but did not kill E. coli after a 2-h exposure. Therefore, the N-short alkyl substituent was more effective for killing E. coli and the N-long alkyl substituent conferred specific bactericidal activity against S. aureus. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Man's Activities on the Marine Environment; Committee on Commerce, United States Senate, Ninety-Fourth Congress, First Session. Committee Print.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Committee on Commerce.

This report, prepared for the Committee on Commerce and the National Ocean Policy Study Committee, describes many aspects of water pollution, both national and international. Specific sections are devoted to: (1) assessing man's influence on the oceans, (2) activities that generate marine pollution, (3) specific marine pollutants, (4) policy for…

Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal Macrophage Activation.

PubMed

Kozicky, Lisa; Sly, Laura M

2017-12-26

Macrophages are phagocytic innate immune cells, which initiate immune responses to pathogens and contribute to healing and tissue restitution. Macrophages are equally important in turning off inflammatory responses. We have shown that macrophages stimulated with intravenous immunoglobulin (IVIg) can produce high amounts of the anti-inflammatory cytokine, interleukin 10 (IL-10), and low levels of pro-inflammatory cytokines in response to bacterial lipopolysaccharides (LPS). IVIg is a polyvalent antibody, primarily immunoglobulin Gs (IgGs), pooled from the plasma of more than 1,000 blood donors. It is used to supplement antibodies in patients with immune deficiencies or to suppress immune responses in patients with autoimmune or inflammatory conditions. Infliximab, a therapeutic anti-tumor necrosis factor alpha (TNFα) antibody, has also been shown to activate macrophages to produce IL-10 in response to inflammatory stimuli. IVIg and other antibody-based biologics can be tested to determine their effects on macrophage activation. This paper describes methods for derivation, stimulation, and assessment of murine bone marrow macrophages activated by antibodies in vitro and murine peritoneal macrophages activated with antibodies in vivo. Finally, we demonstrate the use of western blotting to determine the contribution of specific cell signaling pathways to anti-inflammatory macrophage activity. These protocols can be used with genetically modified mice, to determine the effect of a specific protein(s) on anti-inflammatory macrophage activation. These techniques can also be used to assess whether specific biologics may act by changing macrophages to an IL-10-producing anti-inflammatory activation state that reduces inflammatory responses in vivo. This can provide information on the role of macrophage activation in the efficacy of biologics during disease models in mice, and provide insight into a potential new mechanism of action in people. Conversely, this may caution against the use of specific antibody-based biologics to treat infectious disease, particularly if macrophages play an important role in host defense against that infection.

Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

PubMed Central

Colombo, Miriam; Fiandra, Luisa; Alessio, Giulia; Mazzucchelli, Serena; Nebuloni, Manuela; De Palma, Clara; Kantner, Karsten; Pelaz, Beatriz; Rotem, Rany; Corsi, Fabio; Parak, Wolfgang J.; Prosperi, Davide

2016-01-01

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect. PMID:27991503

The Impact of a Capstone Farm Management Course on Critical Thinking Abilities

ERIC Educational Resources Information Center

Perry, Dustin K.; Paulsen, Thomas H.; Retallick, Michael S.

2015-01-01

Current research demonstrates a need to explore the effects of specific course designs or directed activities on higher education students' critical thinking abilities. Specifically, such research on the effect of an experiential learning-based capstone course is limited. All students (N = 54) enrolled in a capstone farm management course…

Effects of Professional Development on Teachers' Instruction: Results from a Three-year Longitudinal Study.

ERIC Educational Resources Information Center

Desimone, Laura M.; Porter, Andrew C.; Garet, Michael S.; Yoon, Kwang Suk; Birman, Beatrice F.

2002-01-01

Examined the effects of professional development on teachers' instruction using a purposeful sample of about 207 teachers across 5 states for 1996-1999. Professional development focused on specific instructional practices increased teachers' use of those practices in the classroom, and specific features, such as active learning opportunities,…

Item-Specific and Generalization Effects on Brain Activation when Learning Chinese Characters

ERIC Educational Resources Information Center

Deng, Yuan; Booth, James R.; Chou, Tai-Li; Ding, Guo-Sheng; Peng, Dan-Ling

2008-01-01

Neural changes related to learning of the meaning of Chinese characters in English speakers were examined using functional magnetic resonance imaging (fMRI). We examined item specific learning effects for trained characters, but also the generalization of semantic knowledge to novel transfer characters that shared a semantic radical (part of a…

Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes.

PubMed

Li, Jingxia; Zhang, Dongyun; Stoner, Gary D; Huang, Chuanshu

2008-04-01

The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-kappaB or the PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-alpha (TNF-alpha) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects. (c) 2007 Wiley-Liss, Inc.

Differential Effects of Black Raspberry and Strawberry Extracts on BaPDE-Induced Activation of Transcription Factors and Their Target Genes

PubMed Central

Li, Jingxia; Zhang, Dongyun; Stoner, Gary D.; Huang, Chuanshu

2013-01-01

The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor κB (NF-κB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-κB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70S6K and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-κB or the PI-3K/Akt-p70S6K and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-α (TNF-α) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects. PMID:18085529

Brain activations during bimodal dual tasks depend on the nature and combination of component tasks

PubMed Central

Salo, Emma; Rinne, Teemu; Salonen, Oili; Alho, Kimmo

2015-01-01

We used functional magnetic resonance imaging to investigate brain activations during nine different dual tasks in which the participants were required to simultaneously attend to concurrent streams of spoken syllables and written letters. They performed a phonological, spatial or “simple” (speaker-gender or font-shade) discrimination task within each modality. We expected to find activations associated specifically with dual tasking especially in the frontal and parietal cortices. However, no brain areas showed systematic dual task enhancements common for all dual tasks. Further analysis revealed that dual tasks including component tasks that were according to Baddeley's model “modality atypical,” that is, the auditory spatial task or the visual phonological task, were not associated with enhanced frontal activity. In contrast, for other dual tasks, activity specifically associated with dual tasking was found in the left or bilateral frontal cortices. Enhanced activation in parietal areas, however, appeared not to be specifically associated with dual tasking per se, but rather with intermodal attention switching. We also expected effects of dual tasking in left frontal supramodal phonological processing areas when both component tasks required phonological processing and in right parietal supramodal spatial processing areas when both tasks required spatial processing. However, no such effects were found during these dual tasks compared with their component tasks performed separately. Taken together, the current results indicate that activations during dual tasks depend in a complex manner on specific demands of component tasks. PMID:25767443

Characterization of the Regulation and Function of Zinc-Dependent Histone Deacetylases During Mouse Liver Regeneration

PubMed Central

Huang, Jiansheng; Barr, Emily; Rudnick, David A.

2013-01-01

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC mRNA and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA-treatment suppressed the effects of PH on histone deacetylation and hepatocellular BrdU incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. PMID:23258575

The effect of angiotensin 1-7 on tyrosine kinases activity in rat anterior pituitary

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

Rebas, Elzbieta; Zabczynska, Joanna; Lachowicz, Agnieszka

2006-09-01

Angiotensin 1-7 (Ang 1-7) is a peptide originated from Ang II. It is known that in vessels Ang 1-7 shows opposite effects to Ang II. Ang 1-7 can modify processes of proliferation. However, Ang 1-7 action in pituitary gland cells was never studied. Moreover, the specific binding sites for Ang 1-7 are still unknown. The aim of this study was to examine the effects of Ang 1-7 on tyrosine kinases (PTKs) activity in the anterior pituitary. The reaction of phosphorylation was carrying out in presence of different concentration of Ang 1-7 and losartan (antagonist of AT1 receptor) and PD123319 (antagonistmore » of AT2). Our results show that Ang 1-7 inhibited activity of PTK to 60% of basic activity. Losartan did not change the Ang 1-7-induced changes in PTKs activity. The presence of PD123319 together with Ang 1-7 caused stronger inhibition PTKs activity than Ang 1-7 alone. These observations suggest that Ang 1-7 binds to the novel, unknown, specific for this peptide receptor.« less

Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.

PubMed

Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu

2017-08-01

p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO. Notably, DA-specific deletion of p53 provided protection of substantia nigra pars reticulata (SNpr) tyrosine hydroxylase (TH) positive fibers following binge MA, with DAT-p53KO mice having less decline of TH protein levels in striatum versus WT mice. Whereas DAT-p53KO mice demonstrated a consistently higher density of TH fibers in striatum compared to WT mice at 10 days after MA exposure, DA neuron counts within the substantia nigra pars compacta (SNpc) were similar. Finally, supportive of these results, administration of a p53-specific inhibitor (PFT-α) provided a similarly protective effect on MA binge-induced behavioral deficits. Neither DA specific p53 deletion nor p53 pharmacological inhibition affected hyperthermia induced by MA binge. These findings demonstrate a specific contribution of p53 activation in behavioral deficits and DA neuronal terminal loss by MA binge exposure.

Effects of McGill stabilization exercises and conventional physiotherapy on pain, functional disability and active back range of motion in patients with chronic non-specific low back pain.

PubMed

Ghorbanpour, Arsalan; Azghani, Mahmoud Reza; Taghipour, Mohammad; Salahzadeh, Zahra; Ghaderi, Fariba; Oskouei, Ali E

2018-04-01

[Purpose] The aim of this study was to compare the effects of "McGill stabilization exercises" and "conventional physiotherapy" on pain, functional disability and active back flexion and extension range of motion in patients with chronic non-specific low back pain. [Subjects and Methods] Thirty four patients with chronic non-specific low back pain were randomly assigned to McGill stabilization exercises group (n=17) and conventional physiotherapy group (n=17). In both groups, patients performed the corresponding exercises for six weeks. The visual analog scale (VAS), Quebec Low Back Pain Disability Scale Questionnaire and inclinometer were used to measure pain, functional disability, and active back flexion and extension range of motion, respectively. [Results] Statistically significant improvements were observed in pain, functional disability, and active back extension range of motion in McGill stabilization exercises group. However, active back flexion range of motion was the only clinical symptom that statistically increased in patients who performed conventional physiotherapy. There was no significant difference between the clinical characteristics while compared these two groups of patients. [Conclusion] The results of this study indicated that McGill stabilization exercises and conventional physiotherapy provided approximately similar improvement in pain, functional disability, and active back range of motion in patients with chronic non-specific low back pain. However, it appears that McGill stabilization exercises provide an additional benefit to patients with chronic non-specific low back, especially in pain and functional disability improvement.

Transfer after Dual n-Back Training Depends on Striatal Activation Change.

PubMed

Salminen, Tiina; Kühn, Simone; Frensch, Peter A; Schubert, Torsten

2016-09-28

The dual n-back working memory (WM) training paradigm (comprising auditory and visual stimuli) has gained much attention since studies have shown widespread transfer effects. By including a multimodal dual-task component, the task is demanding to the human cognitive system. We investigated whether dual n-back training improves general cognitive resources or a task-specific WM updating process in participants. We expected: (1) widespread transfer effects and the recruitment of a common neuronal network by the training and the transfer tasks and (2) narrower transfer results and that a common activation network alone would not produce transfer, but instead an activation focus on the striatum, which is associated with WM updating processes. The training group showed transfer to an untrained dual-modality WM updating task, but not to single-task versions of the training or the transfer task. They also showed diminished neuronal overlap between the training and the transfer task from pretest to posttest and an increase in striatal activation in both tasks. Furthermore, we found an association between the striatal activation increase and behavioral improvement. The control groups showed no transfer and no change in the amount of activation overlap or in striatal activation from pretest to posttest. We conclude that, instead of improving general cognitive resources (which would have required a transfer effect to all transfer tasks and that a frontal activation overlap between the tasks produced transfer), dual n-back training improved a task-specific process: WM updating of stimuli from two modalities. The current study allows for a better understanding of the cognitive and neural effects of working memory (WM) training and transfer. It shows that dual n-back training mainly improves specific processes of WM updating, and this improvement leads to narrow transfer effects to tasks involving the same processes. On a neuronal level this is accompanied by increased neural activation in the striatum that is related to WM updating. The current findings challenge the view that dual n-back training provokes a general boosting of the WM system and of its neural underpinnings located in frontoparietal brain regions. Instead, the findings imply the relevance of task-specific brain regions which are involved in important cognitive processes during training and transfer tasks. Copyright © 2016 the authors 0270-6474/16/3610198-16$15.00/0.

Focus on Freshman: Basic Instruction Programs Enhancing Physical Activity

ERIC Educational Resources Information Center

Curry, Jarred; Jenkins, Jayne M.; Weatherford, Jennifer

2015-01-01

Physical activity sharply decreases after different life stages, particularly high school graduation to beginning university education. The purpose of this study was to investigate the effect of a specifically designed university physical activity class, Exercise Planning for Freshman (EPF), on students' physical activity and group cohesion…

Extracurricular activities and the development of social skills in children with intellectual and specific learning disabilities.

PubMed

Brooks, B A; Floyd, F; Robins, D L; Chan, W Y

2015-07-01

Children with intellectual disability and specific learning disabilities often lack age-appropriate social skills, which disrupts their social functioning. Because of the limited effectiveness of classroom mainstreaming and social skills training for these children, it is important to explore alternative opportunities for social skill acquisition. Participation in social activities is positively related to children's social adjustment, but little is known about the benefits of activity participation for children with intellectual and specific learning disabilities. This study investigated the association between frequency and type of social activity participation and the social competence of 8-11-year-old children with intellectual disability (n = 40) and specific learning disabilities (n = 53), in comparison with typically developing peers (n = 24). More time involved in unstructured activities, but not structured activities, was associated with higher levels of social competence for all children. This association was strongest for children with intellectual disability, suggesting that participation in unstructured social activities was most beneficial for these children. Future research on the quality of involvement is necessary to further understand specific aspects of unstructured activities that might facilitate social development. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Sex-specific effects of cardiovascular risk factors on endothelium-dependent dilation and endothelin activity in middle-aged women and men.

PubMed

Brar, Vijaywant; Gill, Sartaj; Cardillo, Carmine; Tesauro, Manfredi; Panza, Julio A; Campia, Umberto

2015-01-01

Healthy middle-aged postmenopausal women have higher endothelium-dependent dilation and lower vasoconstrictor activity of endothelin-1 than men. Whether these sex-specific differences extend to patients with cardiovascular risk factors has not been investigated. The current study aimed to determine whether, in patients with cardiovascular risk factors, sex-specific differences exist in endothelium-dependent dilation and endothelin-1 activity. Forearm blood flow responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine, sodium nitroprusside, and the selective endothelin type A receptor blocker BQ-123 in 50 women and 64 men with cardiovascular risk factors. Acetylcholine and sodium nitroprusside induced a significant vasodilation in women and men alike (p < 0.01 for both). Also BQ-123 caused a significant vasodilation (p < 0.001) in both groups. The vasodilator response to acetylcholine was greater in women compared to men; however there were no differences in the response to sodium nitroprusside and BQ-123 (p = NS for both) between the two sex groups. Middle-aged women with cardiovascular risk factors have significantly higher endothelium-dependent dilation than middle-aged men; however, vascular endothelin 1 activity is similar in the two groups. These findings suggest that the presence of cardiovascular risk factors is associated with sex-specific effects on endothelium-dependent dilation but not on endothelin 1 activity. Further study is needed to confirm our findings and to characterize the mechanisms underlying this sex-specific regulation of endothelial function.

Improving Teacher Feedback during Active Learning: Effects of a Professional Development Program

ERIC Educational Resources Information Center

Van den Bergh, Linda; Ros, Anje; Beijaard, Douwe

2014-01-01

This study focuses on improving teacher feedback during active learning. Changing teachers' behavior sustainably, however, is very difficult. Several conditions should be taken into account, and programs should build on teachers' cognitions and practices. Effects of a specifically designed professional development program on 16 elementary…

Effects of Pretests on Children's Numerical Magnitude Representations

ERIC Educational Resources Information Center

Fazio, Lisa K.; Gumbel, Lauren; Robert S. Siegler

2011-01-01

In this experiment, the authors sought to further examine the effects of pretests on later learning. Specifically, they were interested in if activating a correct mental representation on the pretest would improve later learning and if activating an incorrect representation would impair learning. Kindergarteners and preschoolers were split into…

Effects of Biology Teachers' Professional Knowledge and Cognitive Activation on Students' Achievement

ERIC Educational Resources Information Center

Förtsch, Christian; Werner, Sonja; von Kotzebue, Lena; Neuhaus, Birgit J.

2016-01-01

This study examined the effects of teachers' biology-specific dimensions of professional knowledge--pedagogical content knowledge (PCK) and content knowledge (CK)--and cognitively activating biology instruction, as a feature of instructional quality, on students' learning. The sample comprised 39 German secondary school teachers whose lessons on…

Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition

PubMed Central

Popp, Margot; Trumpp, Natalie M.; Kiefer, Markus

2016-01-01

Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance. PMID:28018201

Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

PubMed

Popp, Margot; Trumpp, Natalie M; Kiefer, Markus

2016-01-01

Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

Identification of the Elusive Mammalian Enzyme Phosphatidylcholine-Specific Phospholipase C

DTIC Science & Technology

2014-07-01

are not curative) is that they manifest serious negative side effects , such as heart problems, liver and kidney damage, increased susceptibility to...alternative treatments with a more targeted effect and less harmful side effects . One possible strategy would be to use agents with a narrower...LPS (Zhang et al., 2011) was not reliable/reproducible/specific and that treatment with LPS was not effective in stimulating PC-PLC activity once a

Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

PubMed

Frenk, H

1983-10-01

The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.

Enzymatic Activity of Free-Prostate-Specific Antigen (f-PSA) Is Not Required for Some of its Physiological Activities

PubMed Central

Chadha, Kailash C.; Nair, Bindukumar B.; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L.; Aalinkeel, Ravikumar; Schwartz, Stanley A.; Smith, Gary J.

2015-01-01

BACKGROUND Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+. Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity PMID:21446007

The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves.

PubMed

Balser, Nils; Lorey, Britta; Pilgramm, Sebastian; Naumann, Tim; Kindermann, Stefan; Stark, Rudolf; Zentgraf, Karen; Williams, A Mark; Munzert, Jörn

2014-01-01

In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action-observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task-specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task.

Endometrial nitric oxide synthase activity in mares susceptible or resistant to persistent breeding-induced endometritis and the effect of a specific iNOS inhibitor in vitro.

PubMed

Khan, F A; Chenier, T S; Foster, R A; Hewson, J; Scholtz, E L

2018-06-01

Emerging research suggests that the nitric oxide system may play a role in persistent breeding-induced endometritis (PBIE) in the mare. Differences in uterine nitric oxide (NO) levels between mares susceptible or resistant to PBIE and a dose-dependent inhibitory effect of NO on uterine contractility have been demonstrated. The objectives of this study were to investigate the difference in total nitric oxide synthase (NOS) activity of the endometrium between susceptible and resistant mares and the effect of a specific inducible nitric oxide synthase (iNOS) inhibitor on the endometrial NOS activity in vitro. Six susceptible and six resistant mares were selected based on preset criteria and the results of an intrauterine challenge with killed spermatozoa during oestrus. Endometrial biopsy samples were collected 24 hr post-challenge and cultured at 37°C for 24 hr in L-arginine supplemented minimum essential medium with or without a specific iNOS inhibitor (1,400 W dihydrochloride, 1 mM). The medium and the cultured endometrial tissue were collected after 24 hr of culture and assayed for NO and total protein, respectively. Total NO content of the medium, normalized to endometrial tissue wet weight or total protein, was used as a measure of endometrial NOS activity. Non-parametric tests were applied for statistical analysis. Susceptible mares had significantly greater endometrial NOS activity than resistant mares. The iNOS inhibitor treatment significantly reduced NOS activity in endometrial samples derived from susceptible and resistant mares. These findings provide a basis for in vivo testing of specific iNOS inhibitors as preventative or therapeutic options for PBIE in mares. © 2018 Blackwell Verlag GmbH.

Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

PubMed

Sömjen, D; Weisman, Y; Mor, Z; Harell, A; Kaye, A M

1991-01-01

We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.

Effects of Two Conventional Insecticides on Male-Specific Sex Pheromone Discrimination and Mate Choice in Trichogramma chilonis (Hymenoptera: Trichogrammatidae).

PubMed

Wang, Desen; Lü, Lihua; He, Yurong

2017-04-01

Trichogramma chilonis Ishii is an important natural enemy of many lepidopterous pests on vegetables and field crops. The effects of two conventional insecticides on male-specific sex pheromone discrimination and mate choice in T. chilonis was evaluated in the laboratory. Beta-cypermethrin LC20 exposure induced decreases in male conspecific sex pheromone discrimination and mating rate in T. chilonis, and these decreases were not due to the lower locomotor activity of the surviving T. chilonis males. Spinosad LC20 exposure caused a significant decrease in male locomotor activity of T. chilonis, but did not affect male-specific sex pheromone discrimination (conspecific sex pheromone discrimination or virgin sex pheromone discrimination) or mating rate. However, there was no significant difference in specific sex pheromone discrimination, mate choice, and locomotor activity between control males and males exposed to the low concentration (LC1) of insecticide (beta-cypermethrin or spinosad). In conclusion, beta-cypermethrin LC20 exposure was harmful to male-specific sex pheromone discrimination and mate choice in T. chilonis. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

PubMed Central

Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

2009-01-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

Identification of amino acid residues involved in substrate specificity of plant acyl-ACP thioesterases using a bioinformatics-guided approach

PubMed Central

Mayer, Kimberly M; Shanklin, John

2007-01-01

Background The large amount of available sequence information for the plant acyl-ACP thioesterases (TEs) made it possible to use a bioinformatics-guided approach to identify amino acid residues involved in substrate specificity. The Conserved Property Difference Locator (CPDL) program allowed the identification of putative specificity-determining residues that differ between the FatA and FatB TE classes. Six of the FatA residue differences identified by CPDL were incorporated into the FatB-like parent via site-directed mutagenesis and the effect of each on TE activity was determined. Variants were expressed in E. coli strain K27 that allows determination of enzyme activity by GCMS analysis of fatty acids released into the medium. Results Substitutions at four of the positions (74, 86, 141, and 174) changed substrate specificity to varying degrees while changes at the remaining two positions, 110 and 221, essentially inactivated the thioesterase. The effects of substitutions at positions 74, 141, and 174 (3-MUT) or 74, 86, 141, 174 (4-MUT) were not additive with respect to specificity. Conclusion Four of six putative specificity determining positions in plant TEs, identified with the use of CPDL, were validated experimentally; a novel colorimetric screen that discriminates between active and inactive TEs is also presented. PMID:17201914

Benzil, a potent activator of microsomal epoxide hydrolase in vitro.

PubMed

Seidegård, J; DePierre, J W

1980-12-01

Benzil was found to be a very potent activator of microsomal epoxide hydrolase activity (measured with styrene oxide as substrate) in vitro. The activating effect was uncompetitive and benzil causes approximately ninefold increases in both the apparent V and the apparent Km of the enzyme(s). The half-maximal effect on activity was obtained as a 0.3 mM concentration of benzil. The activating effect obtained with benzil was found to be very specific, since a variety of structurally related compounds had little or no effect on microsomal epoxide hydrolase activity. In order to obtain indications for the existence of more than one microsomal epoxide hydrolase the effect of benzil on this activity from rats induced with phenobarbital, 3-methylcholanthrene, 2-acetylaminofluorene, trans-stilbene oxide, and benzil was tested. The differences observed were minor.

Physical activity, sedentary behaviour and sleep in COPD guidelines: A systematic review

PubMed Central

Effing, Tanja W; Olds, Timothy; Williams, Marie T

2017-01-01

Objectives: Physical activity, sedentary and sleep behaviours have strong associations with health. This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours. Methods: A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005. Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim. The proportions of CPGs providing specific recommendations and strategies were reported. Results: From 2370 citations identified, 35 CPGs were eligible for inclusion. Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep. The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4). Conclusion: Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs. PMID:28774202

Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity

PubMed Central

Erceg, Jelena; Saunders, Timothy E.; Girardot, Charles; Devos, Damien P.; Hufnagel, Lars; Furlong, Eileen E. M.

2014-01-01

Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood. PMID:24391522

Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples

PubMed Central

Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki S.; Halpern, Marnie E.

2014-01-01

Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122:356–362; http://dx.doi.org/10.1289/ehp.1307329 PMID:24425189

Moods as spotlights: the influence of mood on accessibility effects.

PubMed

Avramova, Yana R; Stapel, Diederik A

2008-09-01

Three studies explore the manner in which one's mood may affect the use and impact of accessible information on judgments. Specifically, the authors demonstrated that positive and negative moods differentially influence the direction of accessibility effects (assimilation, contrast) by determining whether abstract traits or concrete actor-trait links are primed. Study 1 investigated the impact of positive versus negative mood on the judgmental impact of trait-implying behaviors and found that positive moods lead to assimilation and negative moods to contrast. In Study 2, this effect was replicated in a subliminal priming paradigm. In Study 3, it was demonstrated that the type of information activated by trait-implying behaviors is indeed mood dependent, such that abstract trait information is activated in a positive mood, whereas specific actor-trait links are activated in a negative mood.

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

PubMed

Martin, Donel M; McClintock, Shawn M; Forster, Jane J; Lo, Tin Yan; Loo, Colleen K

2017-11-01

Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability. © 2017 Wiley Periodicals, Inc.

Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

PubMed

Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

2013-09-01

Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

Inhibitory Effect of Gabaculine on 5-Aminolevulinate Dehydratase Activity in Radish Seedlings 1

PubMed Central

Tchuinmogne, Simo J.; Huault, Claude; Aoues, Abdelkader; Balangé, Alain P.

1989-01-01

We have compared the activity of 5-aminolevulinate dehydratase (5-ALAD) with the amount of protein detected by specific antibodies in rocket immunoelectrophoresis. Parallel kinetic evolutions of enzymic activity and amount of antigen were observed in radish (Raphanus sativus L.) cotyledons, both in complete darkness or under standard far red light involving phytochrome. However, the treatment of seedlings with gabaculine leads to an important decrease in enzymic activity, while the specific protein content is maintained. This inhibition is not overcome by the addition of glutamic acid, but by 5-aminolevulinic acid which points to a specific control of 5-ALAD activity by its substrate. As there is no discrepancy between the enzymic activity and the amount of antigen during the time course development of seedlings, this could confirm a coordinate cellular control between 5-aminolevulinic acid formation and 5-ALAD protein synthesis, both being amplified by the action of phytochrome. PMID:16666925

Changes in Activities of Respiratory Enzymes in Lungs of Guinea-pigs Exposed to Silica Dust: II. Comparison of the Effects of Quartz Dust and Lampblack on the Succinate Oxidase System

PubMed Central

Breyer, Maria G.; Kilroe-Smith, T. A.; Prinsloo, H.

1964-01-01

Kilroe-Smith and Breyer (1963) reported that in the early stages of silicosis in guinea-pigs exposed to the inhalation of quartz dust, before the formation of collagen, there were increases in the specific activities of the complete succinate oxidase system and succinate dehydrogenase. The effects on these enzymes of quartz dust have now been compared with the effects of the fibrogenically `inert' lampblack. Lampblack causes a slight increase in the specific activities of these enzymes but the effects are small compared to those caused by quartz. Lampblack also causes a much smaller increase in lung weight than quartz, thus the enzyme increases are roughly parallel to the rise in lung weight. It appears that the effects observed on the enzymes are part of the general pattern associated with the early stages of the development of silicosis. PMID:14106132

The effect on some enzymes of rat tissue of diets low in fat content.

PubMed

Bartley, W; Dean, B; Taylor, C B; Bailey, E

1967-05-01

1. Rats of two strains were kept on three different diets; one was a commercial diet of rat pellets, one contained about 80% of sucrose and 20% of casein and was supplemented with corn oil, and the third was a similar diet without the corn oil. 2. On the commercial diet, the specific activities of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of one strain of rats (strain A) were 1.5-3 times those in the other strain (strain B). When the diet high in sucrose and supplemented with corn oil was given, there were large increases in the specific activity of pyruvate kinase, glucose 6-phosphate dehydrogenase and fructose 1,6-diphosphatase in the livers of strain A rats. With strain B rats the increases were much smaller. Omission of corn oil from the diet caused a threefold increase in the specific activity of glucose 6-phosphate dehydrogenase in strain B rats, but had little effect on other enzymes. 3. The enzymes of the kidneys and hearts of strain A rats were also more active than those of strain B rats. In strain A rats, the specific activities of pyruvate kinase and fructose 1,6-diphosphatase in the kidney increased when the sucrose content of the diet was high, but in the kidneys of strain B rats there was little change. 4. In strain A rats, the specific activity of pyruvate kinase in the heart more than doubled with the high-sucrose-corn oil diet and increased threefold when corn oil was omitted. No changes were seen in strain B rats. 5. In strain A rats, omission of corn oil from the diet increased the ability of the kidneys to synthesize glucose from lactate. 6. In strain B rats, addition of corn oil to the diet resulted in a decrease in the liver in the specific activity of ATP citrate lyase and in the ability to incorporate acetate into lipid.

Hierarchical activated mesoporous phenolic-resin-based carbons for supercapacitors.

PubMed

Wang, Zhao; Zhou, Min; Chen, Hao; Jiang, Jingui; Guan, Shiyou

2014-10-01

A series of hierarchical activated mesoporous carbons (AMCs) were prepared by the activation of highly ordered, body-centered cubic mesoporous phenolic-resin-based carbon with KOH. The effect of the KOH/carbon-weight ratio on the textural properties and capacitive performance of the AMCs was investigated in detail. An AMC prepared with a KOH/carbon-weight ratio of 6:1 possessed the largest specific surface area (1118 m(2) g(-1)), with retention of the ordered mesoporous structure, and exhibited the highest specific capacitance of 260 F g(-1) at a current density of 0.1 A g(-1) in 1 M H2 SO4 aqueous electrolyte. This material also showed excellent rate capability (163 F g(-1) retained at 20 A g(-1)) and good long-term electrochemical stability. This superior capacitive performance could be attributed to a large specific surface area and an optimized micro-mesopore structure, which not only increased the effective specific surface area for charge storage but also provided a favorable pathway for efficient ion transport. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun; Brown, Alexandra L; Xu, Xihui; Kang, Hyeog; Ke, Hengming; Feng, Xuesong; Ryall, James; Philp, Andrew; Schenk, Simon; Kim, Myung K; Sartorelli, Vittorio; Chung, Jay H

2017-04-01

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1. Published by Elsevier B.V.

Advances in physical activity monitoring and lifestyle interventions in obesity: a review.

PubMed

Bonomi, A G; Westerterp, K R

2012-02-01

Obesity represents a strong risk factor for developing chronic diseases. Strategies for disease prevention often promote lifestyle changes encouraging participation in physical activity. However, determining what amount of physical activity is necessary for achieving specific health benefits has been hampered by the lack of accurate instruments for monitoring physical activity and the related physiological outcomes. This review aims at presenting recent advances in activity-monitoring technology and their application to support interventions for health promotion. Activity monitors have evolved from step counters and measuring devices of physical activity duration and intensity to more advanced systems providing quantitative and qualitative information on the individuals' activity behavior. Correspondingly, methods to predict activity-related energy expenditure using bodily acceleration and subjects characteristics have advanced from linear regression to innovative algorithms capable of determining physical activity types and the related metabolic costs. These novel techniques can monitor modes of sedentary behavior as well as the engagement in specific activity types that helps to evaluate the effectiveness of lifestyle interventions. In conclusion, advances in activity monitoring have the potential to support the design of response-dependent physical activity recommendations that are needed to generate effective and personalized lifestyle interventions for health promotion.

Peroxisome proliferator activated receptor alpha regulates a male-specific cytochrome P450 in mouse liver.

PubMed

Jeffery, Brett; Choudhury, Agharul I; Horley, Neill; Bruce, Mary; Tomlinson, Simon R; Roberts, Ruth A; Gray, Tim J B; Barrett, David A; Shaw, P Nicholas; Kendall, David; Bell, David R

2004-09-15

We set out to find if the strain-specific, male-specific hepatic expression of Cyp4a protein in mouse was due to expression of Cyp4a12 and to understand the genetic basis for reported differences in expression. 12-Lauric acid hydroxylase (LAH) activity was found to show higher levels in male ddY, but not C57Bl/6, mouse liver microsomes. The expression of Cyp4a12 mRNA was studied using RNAase protection assays in male and female liver and kidney of nine mouse strains. Cyp4a12 was found to be highly expressed in male liver and kidney, but at much lower levels in female liver and kidney, in all strains studied. Western blotting with an antibody specific for Cyp4a12 confirmed that Cyp4a12 was expressed in a male specific fashion in C57Bl/6 mouse liver. RNAase protection analysis for Cyp4a10 and 14 in ddY mice revealed that neither of these genes showed male-specific expression. To further investigate genetic factors that control male-specific Cyp4a12 expression, PPARalpha+/+ and -/- mice were studied, showing that total P450 and 12-LAH activity was male-specific in +/+, but not -/- mice. RNAase protection assays were used to confirm that Cyp4a12 was lower in -/- mice. However, the male-specific Slp and MUP-1 genes retained hepatic male-specific levels of expression in +/+ and -/- mice, showing that the decrease in Cyp4a12 was not a general effect on male-specific expression. Thus, PPARalpha has a specific effect on constitutive expression of Cyp4a12.

Tamarixetin Exhibits Anti-inflammatory Activity and Prevents Bacterial Sepsis by Increasing IL-10 Production.

PubMed

Park, Hee Jo; Lee, Seung Jun; Cho, Joon; Gharbi, Amal; Han, Hee Dong; Kang, Tae Heung; Kim, Yangmee; Lee, Yeongjoon; Park, Won Sun; Jung, In Duk; Park, Yeong-Min

2018-06-22

Sepsis is a systemic inflammatory response to pathogenic infection that currently has no specific pharmaceutical interventions. Instead, antibiotics administration is considered the best available option, despite increasing drug resistance. Alternative strategies are therefore urgently required to prevent sepsis and strengthen the host immune system. One such option is tamarixetin (4'- O-methylquercetin), a naturally occurring flavonoid derivative of quercetin that protects against inflammation. The purpose of this study was to determine whether the anti-inflammatory effects of tamarixetin protect against the specific inflammatory conditions induced in lipopolysaccharide (LPS) or Escherichia coli K1 models of sepsis. Our study showed that tamarixetin reduced the secretion of various inflammatory cytokines by dendritic cells after activation with LPS. It also promoted the secretion of the anti-inflammatory cytokine interleukin (IL)-10 and specifically increased the population of IL-10-secreting immune cells in LPS-activated splenocytes. Tamarixetin showed general anti-inflammatory effects in mouse models of bacterial sepsis and decreased bacteria abundance and endotoxin levels. We therefore conclude that tamarixetin has superior anti-inflammatory properties than quercetin during bacterial sepsis. This effect is associated with an increased population of IL-10-secreting immune cells and suggests that tamarixetin could serve as a specific pharmaceutical option to prevent bacterial sepsis.

Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice.

PubMed

Hou, Jue; Zhang, Qicheng; Liu, Zheng; Wang, Shuhui; Li, Dan; Liu, Chang; Liu, Ying; Shao, Yiming

2016-01-01

Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic cell maturation and the subsequent innate immune response when incorporated into an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1 infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA dual expression cassettes stimulated a greater Gag-specific cellular immune response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag-specific T cell response and strong cellular immunity that lasted up to 5 months. In addition, CyPA skewed to cellular rather than humoral immunity. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. The immune response to this vaccine was analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex DNA immunization strategies, and that activity of this adjuvant is specific, broad, long-term, and based on Gag-CyPA interaction.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells.

PubMed

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein.

Health goal priming as a situated intervention tool: how to benefit from nonconscious motivational routes to health behaviour.

PubMed

Papies, Esther K

2016-12-01

Recent research has shown the limited effects of intentions on behaviour, so that novel methods to facilitate behaviour change are needed that do not rely on conscious intentions. Here, it is argued that nonintentional effects on health behaviour, such as the effects of habits, impulses, and nonconscious goals, occur through the activation of cognitive structures by specific situations. Interventions should therefore be situated to change these effects, either by changing the critical cognitive structures (training interventions), or by changing which cognitive structures get activated (cueing interventions). The current article presents this framework for situated interventions, as well as examples of interventions of each type. Then, it introduces goal priming as a cueing intervention tool to activate health goals and thus facilitate healthier behaviour, even in tempting situations that typically activate short-term hedonic goals. Following a review of empirical evidence, five principles for the effective application of health goal primes are proposed, namely (1) to target individuals who value the primed goals, (2) by activating their specific motivation, (3) through effective cues (4) that attract attention at the right time. Finally, (5) an effective goal-directed behaviour needs to be known and accessible to the primed individual. These principles are illustrated with examples of different health behaviours in order to facilitate their application for successful behaviour change.

Health goal priming as a situated intervention tool: how to benefit from nonconscious motivational routes to health behaviour

PubMed Central

Papies, Esther K.

2016-01-01

ABSTRACT Recent research has shown the limited effects of intentions on behaviour, so that novel methods to facilitate behaviour change are needed that do not rely on conscious intentions. Here, it is argued that nonintentional effects on health behaviour, such as the effects of habits, impulses, and nonconscious goals, occur through the activation of cognitive structures by specific situations. Interventions should therefore be situated to change these effects, either by changing the critical cognitive structures (training interventions), or by changing which cognitive structures get activated (cueing interventions). The current article presents this framework for situated interventions, as well as examples of interventions of each type. Then, it introduces goal priming as a cueing intervention tool to activate health goals and thus facilitate healthier behaviour, even in tempting situations that typically activate short-term hedonic goals. Following a review of empirical evidence, five principles for the effective application of health goal primes are proposed, namely (1) to target individuals who value the primed goals, (2) by activating their specific motivation, (3) through effective cues (4) that attract attention at the right time. Finally, (5) an effective goal-directed behaviour needs to be known and accessible to the primed individual. These principles are illustrated with examples of different health behaviours in order to facilitate their application for successful behaviour change. PMID:27144729

Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

PubMed

Sandalova, Elena; Laccabue, Diletta; Boni, Carolina; Tan, Anthony T; Fink, Katja; Ooi, Eng Eong; Chua, Robert; Shafaeddin Schreve, Bahar; Ferrari, Carlo; Bertoletti, Antonio

2010-08-19

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2(low)) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

Unlocking the effects of gender faultlines on team creativity: is activation the key?

PubMed

Pearsall, Matthew J; Ellis, Aleksander P J; Evans, Joel M

2008-01-01

The purpose of this study was to use faultline theory to examine the effects of gender diversity on team creativity. Results from 80 teams working on an idea generation task indicated that the activation of gender faultlines negatively affected the number and overall creativity of ideas. However, gender faultlines that were not activated had no effect. Results also indicated that the relationship between activated gender faultlines and team creativity was partially mediated by the level of conflict within the team. Specifically, emotional conflict partially mediated the effects of activated gender faultlines on the number of ideas generated. Implications are discussed, as well as possible limitations and directions for future research. 2008 APA

Categorization for Faces and Tools—Two Classes of Objects Shaped by Different Experience—Differs in Processing Timing, Brain Areas Involved, and Repetition Effects

PubMed Central

Kozunov, Vladimir; Nikolaeva, Anastasia; Stroganova, Tatiana A.

2018-01-01

The brain mechanisms that integrate the separate features of sensory input into a meaningful percept depend upon the prior experience of interaction with the object and differ between categories of objects. Recent studies using representational similarity analysis (RSA) have characterized either the spatial patterns of brain activity for different categories of objects or described how category structure in neuronal representations emerges in time, but never simultaneously. Here we applied a novel, region-based, multivariate pattern classification approach in combination with RSA to magnetoencephalography data to extract activity associated with qualitatively distinct processing stages of visual perception. We asked participants to name what they see whilst viewing bitonal visual stimuli of two categories predominantly shaped by either value-dependent or sensorimotor experience, namely faces and tools, and meaningless images. We aimed to disambiguate the spatiotemporal patterns of brain activity between the meaningful categories and determine which differences in their processing were attributable to either perceptual categorization per se, or later-stage mentalizing-related processes. We have extracted three stages of cortical activity corresponding to low-level processing, category-specific feature binding, and supra-categorical processing. All face-specific spatiotemporal patterns were associated with bilateral activation of ventral occipito-temporal areas during the feature binding stage at 140–170 ms. The tool-specific activity was found both within the categorization stage and in a later period not thought to be associated with binding processes. The tool-specific binding-related activity was detected within a 210–220 ms window and was located to the intraparietal sulcus of the left hemisphere. Brain activity common for both meaningful categories started at 250 ms and included widely distributed assemblies within parietal, temporal, and prefrontal regions. Furthermore, we hypothesized and tested whether activity within face and tool-specific binding-related patterns would demonstrate oppositely acting effects following procedural perceptual learning. We found that activity in the ventral, face-specific network increased following the stimuli repetition. In contrast, tool processing in the dorsal network adapted by reducing its activity over the repetition period. Altogether, we have demonstrated that activity associated with visual processing of faces and tools during the categorization stage differ in processing timing, brain areas involved, and in their dynamics underlying stimuli learning. PMID:29379426

Categorization for Faces and Tools-Two Classes of Objects Shaped by Different Experience-Differs in Processing Timing, Brain Areas Involved, and Repetition Effects.

PubMed

Kozunov, Vladimir; Nikolaeva, Anastasia; Stroganova, Tatiana A

2017-01-01

The brain mechanisms that integrate the separate features of sensory input into a meaningful percept depend upon the prior experience of interaction with the object and differ between categories of objects. Recent studies using representational similarity analysis (RSA) have characterized either the spatial patterns of brain activity for different categories of objects or described how category structure in neuronal representations emerges in time, but never simultaneously. Here we applied a novel, region-based, multivariate pattern classification approach in combination with RSA to magnetoencephalography data to extract activity associated with qualitatively distinct processing stages of visual perception. We asked participants to name what they see whilst viewing bitonal visual stimuli of two categories predominantly shaped by either value-dependent or sensorimotor experience, namely faces and tools, and meaningless images. We aimed to disambiguate the spatiotemporal patterns of brain activity between the meaningful categories and determine which differences in their processing were attributable to either perceptual categorization per se , or later-stage mentalizing-related processes. We have extracted three stages of cortical activity corresponding to low-level processing, category-specific feature binding, and supra-categorical processing. All face-specific spatiotemporal patterns were associated with bilateral activation of ventral occipito-temporal areas during the feature binding stage at 140-170 ms. The tool-specific activity was found both within the categorization stage and in a later period not thought to be associated with binding processes. The tool-specific binding-related activity was detected within a 210-220 ms window and was located to the intraparietal sulcus of the left hemisphere. Brain activity common for both meaningful categories started at 250 ms and included widely distributed assemblies within parietal, temporal, and prefrontal regions. Furthermore, we hypothesized and tested whether activity within face and tool-specific binding-related patterns would demonstrate oppositely acting effects following procedural perceptual learning. We found that activity in the ventral, face-specific network increased following the stimuli repetition. In contrast, tool processing in the dorsal network adapted by reducing its activity over the repetition period. Altogether, we have demonstrated that activity associated with visual processing of faces and tools during the categorization stage differ in processing timing, brain areas involved, and in their dynamics underlying stimuli learning.

Nonshivering thermogenesis in king penguin chicks. II. Effect of fasting.

PubMed

Duchamp, C; Barré, H; Rouanet, J L; Lanni, A; Cohen-Adad, F; Berne, G; Brebion, P

1991-12-01

The effect of fasting on the energy metabolism of skeletal muscle and liver was investigated in cold-acclimatized short-term fasting (STF) (3 wk) and naturally long-term fasting (LTF) (4-5 mo) king penguin chicks, both groups exhibiting nonshivering thermogenesis (NST). A comparison was made with nourished cold-acclimatized controls. In these chicks, no brown adipose tissue deposits could be found on electron-microscopic observations of fat deposits. Protein content and cytochrome oxidase (CO) activity of tissue homogenates were measured in liver and pectoralis and gastrocnemius muscles, as were protein content, CO activity, and respiration rates of mitochondria isolated from these organs. Fasting-induced protein loss affected the pectoralis more than the gastrocnemius muscle, thus preserving locomotor function. In STF chicks, specific mitochondrial protein content and specific tissue CO activity were preserved but total organ CO capacity was reduced by half in pectoralis and liver following the fall in organ mass. In LTF chicks, both specific and total CO activity were drastically reduced in muscles, whereas specific CO activity was preserved in liver. In these LTF chicks, muscle mitochondria showed an energized configuration associated with an increased area of inner membrane in gastrocnemius. A reduction of respiratory control ratio (RCR) was observed in subsarcolemmal muscle mitochondria of STF chicks, whereas intermyofibrillar and liver mitochondria kept high RCR values.(ABSTRACT TRUNCATED AT 250 WORDS)

Masked Chimeric Antigen Receptor for Tumor-Specific Activation.

PubMed

Han, Xiaolu; Bryson, Paul D; Zhao, Yifan; Cinay, Gunce E; Li, Si; Guo, Yunfei; Siriwon, Natnaree; Wang, Pin

2017-01-04

Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality. To minimize such side effects, we have designed an epidermal growth factor receptor (EGFR)-specific masked CAR (mCAR), which consists of a masking peptide that blocks the antigen-binding site and a protease-sensitive linker. Proteases commonly active in the tumor microenvironment can cleave the linker and disengage the masking peptide, thereby enabling CAR-T cells to recognize target antigens only at the tumor site. In vitro mCAR showed dramatically reduced antigen binding and antigen-specific activation in the absence of proteases, but normal levels of binding and activity upon treatment with certain proteases. Masked CAR-T cells also showed antitumor efficacy in vivo comparable to that of unmasked CAR. Our study demonstrates the feasibility of improving the safety profile of conventional CARs and may also inspire future design of CAR molecules targeting broadly expressed TAAs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Effects of peptides on proliferative activity of retinal and pigmented epithelial cells.

PubMed

Khavinson, V Kh; Zemchikhina, V N; Trofimova, S V; Malinin, V V

2003-06-01

We studied the effects of Retinalamin (polypeptide preparation isolated from the retina) and a synthetic peptide Epithalon (Ala-Glu-Asp-Gly) on proliferative activity of retinal and pigmented epithelial cells. Experiments showed that Retinalamin and Epithalon (in certain concentrations) tissue-specifically stimulated proliferation of retinal and pigmented epithelial cell in culture.

[Functional selectivity of opioid receptors ligands].

PubMed

Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

2010-01-01

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

Glucose and cyclic adenosine monophosphate stimulate activities of adenylate cyclase and guanylate cyclase of Tetrahymena pyriformis infusoria.

PubMed

Shpakov, A O; Derkach, K V; Uspenskaya, Z I

2012-02-01

The sensitivities of cyclase enzymes adenylate cyclase and guanylate cyclase to glucose and extracellular cAMP were studied in Tetrahymena pyriformis infusoria. Glucose effectively stimulated activities of both cyclase enzymes, while cAMP more effectively stimulated adenylate cyclase. It was shown that [6-(14)C]glucose specifically bound to Tetrahymena pyriformis infusoria at dissociation constant (K(D)) and number of binding sites (B(max)) 43 nM and 7.53 fmol glucose per 100,000 cells and [8-(3)H]cAMP bound at 19 nM and 4.46 fmol cAMP per 100,000 cells, respectively. Hence, glucose and cAMP specifically bound to Tetrahymena pyriformis cells and stimulated activities of cyclases in these infusoria.

Effects of traditional medical herbs "minor bupleurum decoction" on the non-specific immune responses of white shrimp (Litopenaeus vannamei).

PubMed

Wu, Yu-Sheng; Lee, Meng-Chou; Huang, Cheng-Ting; Kung, Tzu-Chi; Huang, Chih-Yang; Nan, Fan-Hua

2017-05-01

This study is investigating the effect of minor bupleurum decoction (Xiao-Chai-Hu decoction) on the non-specific immune response of white shrimp (Litopenaeus vannamei). To determine prophenoloxidase activity (proPO), reactive oxygen species production (ROS), superoxide anion production (O 2 - ), nitric oxide production (NO), phagocytic rate (PR), phagocytic index (PI), superoxide dismutase activity (SOD), total haemocyte count (THC) and differential haemocyte count (DHC). In this experiment, treating with different dosages (0, 0.25, 0.5 and, 1%) of minor bupleurum decoction to detect immune parameters on day 0, 1, 2, 4, 7, 14, 21 and 28. Result is shown that 0.25% treatment significantly enhanced the superoxide dismutase (SOD) activity and, 0.25 and 1% treatment significantly increased the ROS production, nitric oxide (NO) production and phagocytic rate (PR) moreover, 0.5 and 1% treatment induced the proPO activity and superoxide anion (O 2 - ) production. Evidence exactly indicated that minor bupleurum decoction is able to enhance the non-specific immunity responses of white shrimp via in vivo examination. Copyright © 2017 Elsevier Ltd. All rights reserved.

AVS-1357 inhibits melanogenesis via prolonged ERK activation.

PubMed

Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Chae, Chong Hak; Park, Kyoung-Chan

2009-08-01

In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.

Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration.

PubMed

Huang, Jiansheng; Barr, Emily; Rudnick, David A

2013-05-01

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC messenger RNA (mRNA) and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however, HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA treatment suppressed the effects of PH on histone deacetylation and hepatocellular bromodeoxyuridine (BrdU) incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. Copyright © 2012 American Association for the Study of Liver Diseases.

Differential effects of developmental hypo- and hyperthyroidism on acetylcholinesterase and butyrylcholinesterase activity in the spinal cord of developing postnatal rat pups.

PubMed

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

2012-11-01

The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby influencing the functional development of this major sensory and motor structure. However, the neurochemical development of glia and other non-neuronal cells, where BuChE is mainly localized, is comparatively unaffected in these abnormal developmental conditions. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Dams and water developments

Treesearch

Robert H. Schueneman

1979-01-01

The U.S. Army Corps of Engineers is involved in the construction and regulation of many activities relating to water resource development. Such activities include dams and reservoirs, channelization and erosion control on rivers and tributaries, and coastal works. These activities can result in an array of visual effects depending on the specific activity type and...

Active Listening in Peer Interviews: The Influence of Message Paraphrasing on Perceptions of Listening Skill

ERIC Educational Resources Information Center

Weger, Harry, Jr.; Castle, Gina R.; Emmett, Melissa C.

2010-01-01

Perhaps no communication skill is identified as regularly as active listening in training programs across a variety of disciplines and activities. Yet little empirical research has examined specific elements of active listening responses in terms of their effectiveness in achieving desired interpersonal outcomes. This study reports an experiment…

Navigating the Active Learning Swamp: Creating an Inviting Environment for Learning.

ERIC Educational Resources Information Center

Johnson, Marie C.; Malinowski, Jon C.

2001-01-01

Reports on a survey of faculty members (n=29) asking them to define active learning, to rate how effectively different teaching techniques contribute to active learning, and to list the three teaching techniques they use most frequently. Concludes that active learning requires establishing an environment rather than employing a specific teaching…

The metabolism of primaquine to its active metabolite is dependent on CYP 2D6.

PubMed

Pybus, Brandon S; Marcsisin, Sean R; Jin, Xiannu; Deye, Gregory; Sousa, Jason C; Li, Qigui; Caridha, Diana; Zeng, Qiang; Reichard, Gregory A; Ockenhouse, Christian; Bennett, Jason; Walker, Larry A; Ohrt, Colin; Melendez, Victor

2013-06-20

The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites. In the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity. PQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice. These results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.

Protective antitumor activity through dendritic cell immunization is mediated by NK cell as well as CTL activation.

PubMed

Kim, K D; Kim, J K; Kim, S J; Choe, I S; Chung, T H; Choe, Y K; Lim, J S

1999-08-01

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells, which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with bone marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocultured DCs was able to induce complete protective immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DCs induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be useful for designing tumor vaccines using DCs when the information about tumor antigens is limited.

Effects of microwave heating on porous structure of regenerated powdered activated carbon used in xylose.

PubMed

Li, Wei; Wang, Xinying; Peng, Jinhui

2014-01-01

The regeneration of spent powdered activated carbons used in xylose decolourization by microwave heating was investigated. Effects of microwave power and microwave heating time on the adsorption capacity of regenerated activated carbons were evaluated. The optimum conditions obtained are as follows: microwave power 800W; microwave heating time 30min. Regenerated activated carbon in this work has high adsorption capacities for the amount of methylene blue of 16 cm3/0.1 g and the iodine number of 1000.06mg/g. The specific surface areas of fresh commercial activated carbon, spent carbon and regenerated activated carbon were calculated according to the Brunauer, Emmett and Teller method, and the pore-size distributions of these carbons were characterized by non-local density functional theory (NLDFT). The results show that the specific surface area and the total pore volume of regenerated activated carbon are 1064 m2/g and 1.181 mL/g, respectively, indicating the feasibility of regeneration of spent powdered activated carbon used in xylose decolourization by microwave heating. The results of surface fractal dimensions also confirm the results of isotherms and NLDFT.

The effect of active video games on cognitive functioning in clinical and non-clinical populations: A meta-analysis of randomized controlled trials.

PubMed

Stanmore, Emma; Stubbs, Brendon; Vancampfort, Davy; de Bruin, Eling D; Firth, Joseph

2017-07-01

Physically-active video games ('exergames') have recently gained popularity for leisure and entertainment purposes. Using exergames to combine physical activity and cognitively-demanding tasks may offer a novel strategy to improve cognitive functioning. Therefore, this systematic review and meta-analysis was performed to establish effects of exergames on overall cognition and specific cognitive domains in clinical and non-clinical populations. We identified 17 eligible RCTs with cognitive outcome data for 926 participants. Random-effects meta-analyses found exergames significantly improved global cognition (g=0.436, 95% CI=0.18-0.69, p=0.001). Significant effects still existed when excluding waitlist-only controlled studies, and when comparing to physical activity interventions. Furthermore, benefits of exergames where observed for both healthy older adults and clinical populations with conditions associated with neurocognitive impairments (all p<0.05). Domain-specific analyses found exergames improved executive functions, attentional processing and visuospatial skills. The findings present the first meta-analytic evidence for effects of exergames on cognition. Future research must establish which patient/treatment factors influence efficacy of exergames, and explore neurobiological mechanisms of action. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

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

Zhu, Jingmin

2017-01-01

The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003more » is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions. - Highlights: • UVI3003 is a RXRs antagonist and shows teratogenicity to Xenopus embryos. • UVI3003 activated xPPARγ either in Cos7 cells or Xenopus embryos. • UVI3003 did not activate human or mouse PPARγ in Cos7 cells. • Activating PPARγ leads to teratogenic effects in Xenopus embryos.« less

Atomic Layer-by-Layer Deposition of Pt on Pd Nanocubes for Catalysts with Enhanced Activity and Durability toward Oxygen Reduction

DOE PAGES

Xie, Shuifen; Choi, Sang -Il; Lu, Ning; ...

2014-05-05

Here, an effective strategy for reducing the Pt content while retaining the activity of a Pt-based catalyst is to deposit the Pt atoms as ultrathin skins of only a few atomic layers thick on nanoscale substrates made of another metal. During deposition, however, the Pt atoms often take an island growth mode because of a strong bonding between Pt atoms. Here we report a versatile route to the conformal deposition of Pt as uniform, ultrathin shells on Pd nanocubes in a solution phase. The introduction of the Pt precursor at a relatively slow rate and high temperature allowed the depositedmore » Pt atoms to spread across the entire surface of a Pd nanocube to generate a uniform shell. The thickness of the Pt shell could be controlled from one to six atomic layers by varying the amount of Pt precursor added into the system. Compared to a commercial Pt/C catalyst, the Pd@Pt nL (n = 1–6) core–shell nanocubes showed enhancements in specific activity and durability toward the oxygen reduction reaction (ORR). Density functional theory (DFT) calculations on model (100) surfaces suggest that the enhancement in specific activity can be attributed to the weakening of OH binding through ligand and strain effects, which, in turn, increases the rate of OH hydrogenation. A volcano-type relationship between the ORR specific activity and the number of Pt atomic layers was derived, in good agreement with the experimental results. Both theoretical and experimental studies indicate that the ORR specific activity was maximized for the catalysts based on Pd@Pt 2–3L nanocubes. Because of the reduction in Pt content used and the enhancement in specific activity, the Pd@Pt 1L nanocubes showed a Pt mass activity with almost three-fold enhancement relative to the Pt/C catalyst.« less

Modulating the activity of protein conjugated to gold nanoparticles by site-directed orientation and surface density of bound protein.

PubMed

Liu, Feng; Wang, Lei; Wang, Hongwei; Yuan, Lin; Li, Jingwen; Brash, John Law; Chen, Hong

2015-02-18

The key property of protein-nanoparticle conjugates is the bioactivity of the protein. The ability to accurately modulate the activity of protein on the nanoparticles at the interfaces is important in many applications. In the work reported here, modulation of the activity of protein-gold nanoparticle (AuNP) conjugates by specifically orienting the protein and by varying the surface density of the protein was investigated. Different orientations were achieved by introducing cysteine (Cys) residues at specific sites for binding to gold. We chose Escherichia coli inorganic pyrophosphatase (PPase) as a model protein and used site-directed mutagenesis to generate two mutant types (MTs) with a single Cys residue on the surface: MT1 with Cys near the active center and MT2 with Cys far from the active center. The relative activities of AuNP conjugates with wild type (WT), MT1, and MT2 were found to be 44.8%, 68.8%, and 91.2% of native PPase in aqueous solution. Site-directed orientation with the binding site far from the active center thus allowed almost complete preservation of the protein activity. The relative activity of WT and MT2 conjugates did not change with the surface density of the protein, while that of MT1 increased significantly with increasing surface density. These results demonstrate that site-directed orientation and surface density can both modulate the activity of proteins conjugated to AuNP and that orientation has a greater effect than density. Furthermore, increasing the surface density of the specifically oriented protein MT2, while having no significant effect on the specific activity of the protein, still allowed increased protein loading on the AuNP and thus increased the total protein activity. This is of great importance in the study on the interface of protein and nanoparticle and the applications for enzyme immobilization, drug delivery, and biocatalysis.

Ultrasound Stimulation of Different Dental Stem Cell Populations: Role of Mitogen-activated Protein Kinase Signaling.

PubMed

Gao, Qianhua; Walmsley, A Damien; Cooper, Paul R; Scheven, Ben A

2016-03-01

Mesenchymal stem cells (MSCs) from dental tissues may respond to low-intensity pulsed ultrasound (LIPUS) treatment, potentially providing a therapeutic approach to promoting dental tissue regeneration. This work aimed to compare LIPUS effects on the proliferation and MAPK signaling in MSCs from rodent dental pulp stem cells (DPSCs) compared with MSCs from periodontal ligament stem cells (PDLSCs) and bone marrow stem cells (BMSCs). Isolated MSCs were treated with 1-MHz LIPUS at an intensity of 250 or 750 mW/cm2 for 5 or 20 minutes. Cell proliferation was evaluated by 5-bromo-2-deoxyuridine (BrdU) staining after 24 hours of culture following a single LIPUS treatment. Specific ELISAs were used to determine the total and activated p38, ERK1/2, and JNK MAPK signaling proteins up to 4 hours after treatment. Selective MAPK inhibitors PD98059 (ERK1/2), SB203580 (p38), and SP600125 (JNK) were used to determine the role of activation of the particular MAPK pathways. The proliferation of all MSC types was significantly increased after LIPUS treatment. LIPUS at a 750-mW/cm2 dose induced the greatest effects on DPSCs. BMSC proliferation was stimulated in equal measures by both intensities, whereas 250 mW/cm2 LIPUS exposure exerted maximum effects on PDLSCs. ERK1/2 was activated immediately in DPSCs after treatment. Concomitantly, DPSC proliferation was specifically modulated by ERK1/2 inhibition, whereas p38 and JNK inhibition exerted no effects. In BMSCs, JNK MAPK signaling was LIPUS activated, and the increase in proliferation was blocked by specific inhibition of the JNK pathway. In PDLSCs, JNK MAPK signaling was activated immediately after LIPUS, whereas p-p38 MAPK increased significantly in these cells 4 hours after exposure. Correspondingly, JNK and p38 inhibition modulated LIPUS-stimulated PDLSC proliferation. LIPUS promoted MSC proliferation in an intensity and cell-specific dependent manner via activation of distinct MAPK pathways. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Priming of disability and elderly stereotype in motor performance: similar or specific effects?

PubMed

Ginsberg, Frederik; Rohmer, Odile; Louvet, Eva

2012-04-01

In three experimental studies, the effects of priming participants with the disability stereotype were investigated with respect to their subsequent motor performance. Also explored were effects of activating two similar stereotypes, persons with a disability and elderly people. In Study 1, participants were primed with the disability stereotype versus with a neutral prime, and then asked to perform on a motor coordination task. In Studies 2 and 3, a third condition was introduced: priming participants with the elderly stereotype. Results indicated that priming participants with the disability stereotype altered their motor performance: they showed decreased manual dexterity and performed slower than the non-primed participants. Priming with the elderly stereotype decreased only performance speed. These findings underline that prime-to-behavior effects may depend on activation of specific stereotype content.

Sports and Child Development

PubMed Central

2016-01-01

The role of curricular activities for the formation of education, health and behavioural outcomes has been widely studied. Yet, the role of extra-curricular activities has received little attention. This study analyzes the effect of participation in sports clubs—one of the most popular extra-curricular activities among children. We use alternative datasets and flexible semi-parametric estimation methods with a specific way to use the panel dimension of the data to address selection into sports. We find positive and robust effects on children’s school performance and peer relations. Crowding out of passive leisure activities can partially explain the effects. PMID:27144474

Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes.

PubMed

Fang, Yan; Gao, Na; Tian, Xin; Zhou, Jun; Zhang, Hai-Feng; Gao, Jie; He, Xiao-Pei; Wen, Qiang; Jia, Lin-Jing; Jin, Han; Qiao, Hai-Ling

2018-06-27

Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes. We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph. We found that the effects of the 18 POR SNPs on 10 CYP activities were CYP genotype-dependent. The POR mutations were significantly associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by these POR SNPs. Notably, the effect of a specific POR mutation on the activity of a CYP genotype could not be predicted from other CYP genotypes of even the same CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was uncovered, which was not necessarily consistent with the effect of either single POR SNP. The effects of POR SNPs on CYP activities were not only CYP-dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of a POR SNP alone and in combination with other POR SNPs (MSGP) was not always consistent, nor predictable. Understanding the impact of POR gene polymorphisms on drug metabolism necessitates knowing the complete SNP complement of POR and the genotype of the relevant CYPs. © 2018 The Author(s). Published by S. Karger AG, Basel.

Inhibitory effect of cyanide on wastewater nitrification determined using SOUR and RNA-based gene-specific assays.

PubMed

Kapoor, V; Elk, M; Li, X; Santo Domingo, J W

2016-08-01

The effect of cyanide (CN(-) ) on nitrification was examined with samples from nitrifying bacterial enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN(-) used in the batch assays were 0·03, 0·06, 0·1 and 1·0 mg l(-1) . There was considerable decrease in SOUR with increasing dosages of CN(-) . A decrease of more than 50% in nitrification activity was observed at 0·1 mg l(-1) CN(-) . Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN(-) dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric haeme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA-based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. The effect of cyanide on nitrifying bacteria was characterized by measuring physiological and transcriptional response. Cyanide was inhibitory to nitrification at concentrations that may be found in industrial waste. The RNA-based function-specific assays represent a mechanistic approach for better understanding the effect of toxic compounds on nitrification activity in wastewater. Moreover, the relative abundance of RNA transcripts can be used to closely track in situ nitrifying bacterial activity which can be used to predict inhibition events, thereby providing a metric to potentially improve performance of wastewater nitrifying systems. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

A Survey of Enzymatic Activity in Commercially Available Pool and Spa Products

USDA-ARS?s Scientific Manuscript database

Many pool water treatment products currently available commercially claim that they work effectively by possessing enzyme activity (specifically lipase) that degrades common oil (lipid) contaminants found in pool water. Currently, there is no standard in measuring the enzymatic activity of these enz...

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Evaluation of anti-allergic properties of caffeic acid phenethyl ester in a murine model of systemic anaphylaxis

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

Park, Sae-Gwang; Lee, Da-Young; Seo, Su-Kil

Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. It has several positive effects, including anti-inflammatory, anti-oxidation, anti-cancer, anti-bacterial, anti-viral, anti-fungal, and immunomodulatory effects. In particular, the suppressive effect of NF-{kappa}B may disrupt a component of allergic induction. The principal objective of this experimental study was to evaluate the effects of CAPE on the active systemic anaphylaxis induced by ovalbumin (OVA) challenge in mice. Mice were intraperitoneally sensitized and intravenously challenged with OVA. Histopathological analysis, nuclear factor (NF)-{kappa}B activation, and the plasma levels of histamine and total IgE after allergen challenge were evaluated. After challenges, allmore » of the sham-treated mice developed anaphylactic symptoms, increased plasma levels of histamine and OVA-specific IgE, marked vascular leakage, NF-{kappa}B activation, platelet-activating factor (PAF) production, and histological changes including pulmonary edema and hemorrhage in the renal medullae within 20 min. By way of contrast, a reduction in the plasma levels of histamine and OVA-specific IgE and an inhibition of NF-{kappa}B activation and PAF release were observed in the CAPE-treated mice. In addition, a significant prevention of hemoconcentration and OVA-induced pathological changes were noted. These results indicate that CAPE demonstrates an anti-allergic effect, which may be the result of its protective effects against IgE-mediated allergy.« less

Fetal growth restriction promotes physical inactivity and obesity in female mice.

PubMed

Baker, M S; Li, G; Kohorst, J J; Waterland, R A

2015-01-01

Environmental exposures during critical periods of prenatal and early postnatal life affect the development of mammalian body weight regulatory mechanisms, influencing lifelong risk of obesity. The specific biological processes that mediate the persistence of such effects, however, remain poorly understood. The objectives of this study were to determine the developmental timing and physiological basis of the obesity-promoting effect previously reported in offspring of obese agouti viable yellow (A(vy)/a) mothers. Newborn offspring of obese A(vy)/a and lean (a/a) mothers were cross-fostered shortly after birth to study separately the effects of in utero or suckling period exposure to A(vy)/a dams. Body composition, food intake, physical activity and energy expenditure were measured in offspring shortly after weaning and in adulthood. Offspring of obese A(vy)/a dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically in females. Our main analyses focused on wild-type (a/a) offspring, because a subset of adult A(vy)/a offspring contracted a kidney disease resembling diabetic nephropathy. Detailed physiological characterization demonstrated that, both shortly after weaning and in adulthood, female wild-type mice born to A(vy)/a mothers are not hyperphagic but have reduced physical activity and energy expenditure. No such coordinated changes were detected in male offspring. Mediational regression analysis of our longitudinal data supported a causal pathway in which fetal growth restriction persistently reduces physical activity, leading to adult obesity. Our data are consistent with several recent human epidemiological studies showing female-specific effects of perinatal nutritional restriction on later obesity, and provide the novel mechanistic insight that this may occur via permanent and sex-specific changes in one's inherent propensity for physical activity.

How children use drawing to regulate their emotions.

PubMed

Drake, Jennifer E; Winner, Ellen

2013-01-01

We examined two ways in which drawing may function to elevate mood in children-venting (expressing negative feelings) and distraction (expressing something unrelated to the negative feelings). We examined the effectiveness of drawing as an emotion regulator when drawing is used to vent versus distract (Study 1) and tested whether the effects found are specific to the activity of creating one's own drawing or generalisable to a drawing activity in which children had to copy another's drawing (Study 2). To induce a negative mood, we asked children to think of a disappointing event. Mood was assessed before and after the assigned activity. In both studies, mood improved significantly more in the distract than in the vent or copy condition. Study 1 demonstrates that drawing improves mood in children via distraction and not via venting. Study 2 demonstrates that this effect is specific to a drawing task in which an image is freely constructed. When a copying task is used, the effect disappears.

Extraction and quantitation of coumarin from cinnamon and its effect on enzymatic browning in fresh apple juice: a bioinformatics approach to illuminate its antibrowning activity.

PubMed

Thada, Rajarajeshwari; Chockalingam, Shivashri; Dhandapani, Ramesh Kumar; Panchamoorthy, Rajasekar

2013-06-05

Enzymatic browning by polyphenoloxidase (PPO) affects food quality and taste in fruits and vegetables. Thus, the study was designed to reduce browning in apple juice by coumarin. The ethanolic extract of cinnamon was prepared and its coumarin content was quantitated by HPLC, using authentic coumarin (AC) as standard. The effect of cinnamon extract (CE) and AC on enzymatic browning, its time dependent effects, and the specific activity of PPO and peroxidase (POD) were studied in apple juice. The docking of coumarin with PPO and POD was also performed to elucidate its antibrowning mechanism. The CE (73%) and AC (82%) showed better reduction in browning, maintained its antibrowning effect at all time points, and significantly (p < 0.05) reduced the specific activity of PPO and POD when compared with controls. Coumarin showed strong interaction with binding pockets of PPO and POD, suggesting its potential use as inhibitor to enzyme mediated browning in apple juice.

Positive Emotional Effects of Leisure in Green Spaces in Alleviating Work–Family Spillover in Working Mothers

PubMed Central

Chang, Po-Ju; Bae, So Young

2017-01-01

Studies have shown that family and work spillover affects well-being and that leisure activities can alleviate the negative effects of work-related stress on health. However, few studies have focused on investigating the effects of specific leisure activities among specific populations. To examine whether leisure activities in green spaces can promote individual recovery processes and alleviate the effects of work and family spillover on positive emotions, this study applied the effort-recovery model to a population of working mothers. Through online and paper questionnaires, sample data were collected from 221 working mothers in Taiwan. Structural equation modeling was used to test the experimental hypothesis, and mediation analysis was used to determine whether leisure in green spaces is a mediating factor. The results indicated that leisure in green spaces is a mediator of the relationship of negative work and family spillover with positive emotions. In addition, strolls and park visits were found to provide greater psychological benefits to working mothers, compared with picnics. PMID:28696388

Positive Emotional Effects of Leisure in Green Spaces in Alleviating Work-Family Spillover in Working Mothers.

PubMed

Chang, Po-Ju; Bae, So Young

2017-07-11

Studies have shown that family and work spillover affects well-being and that leisure activities can alleviate the negative effects of work-related stress on health. However, few studies have focused on investigating the effects of specific leisure activities among specific populations. To examine whether leisure activities in green spaces can promote individual recovery processes and alleviate the effects of work and family spillover on positive emotions, this study applied the effort-recovery model to a population of working mothers. Through online and paper questionnaires, sample data were collected from 221 working mothers in Taiwan. Structural equation modeling was used to test the experimental hypothesis, and mediation analysis was used to determine whether leisure in green spaces is a mediating factor. The results indicated that leisure in green spaces is a mediator of the relationship of negative work and family spillover with positive emotions. In addition, strolls and park visits were found to provide greater psychological benefits to working mothers, compared with picnics.

A specific multi-nutrient formulation enhances M1 muscarinic acetylcholine receptor responses in vitro.

PubMed

Savelkoul, Paul J M; Janickova, Helena; Kuipers, Almar A M; Hageman, Robert J J; Kamphuis, Patrick J; Dolezal, Vladimir; Broersen, Laus M

2012-02-01

Recent evidence indicates that supplementation with a specific combination of nutrients may affect cell membrane synthesis and composition. To investigate whether such nutrients may also modify the physical properties of membranes, and affect membrane-bound processes involved in signal transduction pathways, we studied the effects of nutrient supplementation on G protein-coupled receptor activation in vitro. In particular, we investigated muscarinic receptors, which are important for the progression of memory deterioration and pathology of Alzheimer's disease. Nerve growth factor differentiated pheochromocytoma cells that were supplemented with specific combinations of nutrients showed enhanced responses to muscarinic receptor agonists in a membrane potential assay. The largest effects were obtained with a combination of nutrients known as Fortasyn™ Connect, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate as a uridine source, choline, vitamin B6, vitamin B12, folic acid, phospholipids, vitamin C, vitamin E, and selenium. In subsequent experiments, it was shown that the effects of supplementation could not be attributed to single nutrients. In addition, it was shown that the agonist-induced response and the supplement-induced enhancement of the response were blocked with the muscarinic receptor antagonists atropine, telenzepine, and AF-DX 384. In order to determine whether the effects of Fortasyn™ Connect supplementation were receptor subtype specific, we investigated binding properties and activation of human muscarinic M1, M2 and M4 receptors in stably transfected Chinese hamster ovary cells after supplementation. Multi-nutrient supplementation did not change M1 receptor density in plasma membranes. However, M1 receptor-mediated G protein activation was significantly enhanced. In contrast, supplementation of M2- or M4-expressing cells did not affect receptor signaling. Taken together, these results indicate that a specific combination of nutrients acts synergistically in enhancing muscarinic M1 receptor responses, probably by facilitating receptor-mediated G protein activation. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Prior probability modulates anticipatory activity in category-specific areas.

PubMed

Trapp, Sabrina; Lepsien, Jöran; Kotz, Sonja A; Bar, Moshe

2016-02-01

Bayesian models are currently a dominant framework for describing human information processing. However, it is not clear yet how major tenets of this framework can be translated to brain processes. In this study, we addressed the neural underpinning of prior probability and its effect on anticipatory activity in category-specific areas. Before fMRI scanning, participants were trained in two behavioral sessions to learn the prior probability and correct order of visual events within a sequence. The events of each sequence included two different presentations of a geometric shape and one picture of either a house or a face, which appeared with either a high or a low likelihood. Each sequence was preceded by a cue that gave participants probabilistic information about which items to expect next. This allowed examining cue-related anticipatory modulation of activity as a function of prior probability in category-specific areas (fusiform face area and parahippocampal place area). Our findings show that activity in the fusiform face area was higher when faces had a higher prior probability. The finding of a difference between levels of expectations is consistent with graded, probabilistically modulated activity, but the data do not rule out the alternative explanation of a categorical neural response. Importantly, these differences were only visible during anticipation, and vanished at the time of stimulus presentation, calling for a functional distinction when considering the effects of prior probability. Finally, there were no anticipatory effects for houses in the parahippocampal place area, suggesting sensitivity to stimulus material when looking at effects of prediction.

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV

PubMed Central

Carbone, Javier

2016-01-01

Abstract The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection. PMID:26900990

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV.

PubMed

Carbone, Javier

2016-03-01

The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection.

Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

PubMed

Bulla, O; Poncet, A; Alberio, L; Asmis, L M; Gähler, A; Graf, L; Nagler, M; Studt, J-D; Tsakiris, D A; Fontana, P

2017-07-01

Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard. © 2017 John Wiley & Sons Ltd.

The effect of CO2 activation temperature on the physical and electrochemical properties of activated carbon monolith from banana stem waste

NASA Astrophysics Data System (ADS)

Taer, E.; Susanti, Y.; Awitdrus, Sugianto, Taslim, R.; Setiadi, R. N.; Bahri, S.; Agustino, Dewi, P.; Kurniasih, B.

2018-02-01

The effect of CO2 activation on the synthesis of activated carbon monolith from banana stem waste has been studied. Physical characteristics such as density, degree of crystallinity, surface morphology and elemental content has been analyzed, supporting the finding of an excellent electrochemical properties for the supercapacitor. The synthesis of activated carbon electrode began with pre-carbonization process at temperature of 250°C for 2.5 h. Then the process was continued by chemical activation using KOH as activating agent with a concentration of 0.4 M. The pellets were formed with 8 ton hydrolic pressure. All the samples were carbonized at a temperature of 600°C, followed by physical activation using CO2 gas at a various temperatures ranging from 800°C, 850°C, 900°C and 950°C for 2 h. The carbon content was increased with increasing temperature and the optimum temperature was 900°C. The specific capacitance depends on the activation temperature with the highest specific capacitance of 104.2 F/g at the activation temperature of 900°C.

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2010 CFR

2010-10-01

... polar bear or Pacific walrus in execution of those activities and you want nonlethal incidental take... Operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bear and... measures to minimize adverse effects on the availability of polar bear and Pacific walrus for subsistence...

Effect of Seasonal Changes in Soil Temperature and Moisture on Wood Consumption and Foraging Activity of the Formosan Subterranean Termite (Isoptera: Rhinotermitidae)

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine whether seasonal changes cause significant effects on the foraging activity and wood consumption of C. formosanus in New Orleans and how changes in specific climatic variables affect termite foraging behavior. There was a significant correlation between w...

Beyond Rhyme or Reason: ERPs Reveal Task-Specific Activation of Orthography on Spoken Language

ERIC Educational Resources Information Center

Pattamadilok, Chotiga; Perre, Laetitia; Ziegler, Johannes C.

2011-01-01

Metaphonological tasks, such as rhyme judgment, have been the primary tool for the investigation of the effects of orthographic knowledge on spoken language. However, it has been recently argued that the orthography effect in rhyme judgment does not reflect the automatic activation of orthographic codes but rather stems from sophisticated response…

[Changes in proline-specific peptidase activity in experimental model of retrograde amnesia].

PubMed

Nazarova, G A; Zolotov, N N; Krupina, N A; Kraĭneva, V A; Garibova, T L; Voronina, T A

2007-01-01

Changes in proline-specific peptidase activity in the frontal cortex and hippocampus were studied using the experimental model of retrograde amnesia in rats. In one group, the amnesia was produced by a single injection of M-cholinergic antagonist scopolamine and the other group received the maximal electroconvulsive stimulation (MES). The amnesic effect was evaluated in passive avoidance test. In the amnesia models under consideration, the activity of prolylendopeptidase was significantly increased in both frontal cortex and hippocampus. The activity of dipeptidyl peptidase IV was significantly decreased in the cortex, whereas in the hippocampus it remained unchanged. Pyracetam inhibited prolylendopeptidase in the cortex and hippocampus, whereas dipeptidyl peptidase IV activity remained unchanged.

GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients.

PubMed

Pihl, Mikael; Barcenilla, Hugo; Axelsson, Stina; Chéramy, Mikael; Åkerman, Linda; Johansson, Ingela; Ludvigsson, Johnny; Casas, Rosaura

2017-03-01

Administration of Glutamic Acid Decarboxylase (GAD) 65 formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD 65 -induced proliferation, and frequencies of T cells with a GAD 65 -specific TCR in Swedes participating in the trial. Stimulation with GAD 65 induced activated T cells and also cells with a suppressive phenotype. Activated GAD 65 -specific effector T cells were detected by tetramer staining while the frequency of GAD 65 -specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25 + CD127 + , but had no effect on CD25 hi CD127 lo . Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD 65 -specific cells were mainly of activated phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities.

PubMed

Luo, Weiming; Tweedie, David; Beedie, Shaunna L; Vargesson, Neil; Figg, William D; Greig, Nigel H; Scerba, Michael T

2018-05-01

A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF-α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF-α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF-α. Notable anti-angiogenesis activity was observed for 20, 21 and 22. Published by Elsevier Ltd.

Activation of mixed glia by Abeta-specific Th1 and Th17 cells and its regulation by Th2 cells.

PubMed

McQuillan, K; Lynch, Marina A; Mills, Kingston H G

2010-05-01

Microglia are innate immune cells of the CNS, that act as antigen-presenting cells (APC) for antigen-specific T cells and respond to inflammatory stimuli, such as amyloid-beta (Abeta), resulting in the release of neurotoxic factors and pro-inflammatory cytokines. Astrocytes can also act as APC and modulate the function of microglia. However, the role of distinct T cell subtypes, in particular Th17 cells, in glial activation and subsequent modulatory effects of Th2 cells are poorly understood. Here, we generated Abeta-specific Th1, Th2, and Th17 cells and examined their role in modulating Abeta-induced activation of microglia in a mixed glial culture, a preparation which mimics the complex APC types in the brain. We demonstrated that mixed glia acted as an effective APC for Abeta-specific Th1 and Th17 cells. Addition of Abeta-specific Th2 cells suppressed the Abeta-induced IFN-gamma production by Th1 cells and IL-17 production by Th17 cells with glia as the APC. Co-culture of Abeta-specific Th1 or Th17 cells with glia markedly enhanced Abeta-induced pro-inflammatory cytokine production and expression of MHC class II and co-stimulatory molecules on the microglia. Addition of Abeta-specific Th2 cells inhibited Th17 cell-induced IL-1beta and IL-6 production by mixed glia and attenuated Th1 cell-induced CD86 and CD40 expression on microglia. The modest enhancement of MHC class II and CD86 expression on astrocytes by Abeta-specific Th1 and Th17 was not attenuated by Th2 cells. These data indicate that Abeta-specific Th1 and Th17 cells induce inflammatory activation of glia, and that this is in part regulated by Th2 cells. Copyright 2010 Elsevier Inc. All rights reserved.

Estrogen modulation properties of mangiferin and quercetin and the mangiferin metabolite norathyriol.

PubMed

Wilkinson, Ashley S; Taing, Meng-Wong; Pierson, Jean Thomas; Lin, Chun-Nam; Dietzgen, Ralf G; Shaw, P Nicholas; Gidley, Michael J; Monteith, Gregory R; Roberts-Thomson, Sarah J

2015-06-01

Mango fruit contain many bioactive compounds, some of which are transcription factor regulators. Estrogen receptor alpha (ERα) and beta (ERβ) are two regulators of gene transcription that are important in a variety of physiological processes and also in diseases including breast cancer. We examined the ability of the mango constituents quercetin, mangiferin, and the aglycone form of mangiferin, norathyriol, to activate both isoforms of the estrogen receptor. Quercetin and norathyriol decreased the viability of MCF-7 breast cancer cells whereas mangiferin had no effect on MCF-7 cells. We also determined that quercetin and mangiferin selectively activated ERα whereas norathyriol activated both ERα and ERβ. Despite quercetin, mangiferin and norathyriol having similar polyphenolic structural motifs, only norathyriol activated ERβ, showing that bioactive agents in mangoes have very specific biological effects. Such specificity may be important given the often-opposing roles of ERα and ERβ in breast cancer proliferation and other cellular processes.

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

PubMed

Iremashvili, Viacheslav; Barney, Shane L; Manoharan, Murugesan; Kava, Bruce R; Parekh, Dipen J; Punnen, Sanoj

2016-04-01

To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance. © 2016 The Japanese Urological Association.

Utilizing high-throughput bioassays associated with US EPA ToxCast Program to assess biological activity of environmental contaminants: A case study of chemical mixtures

EPA Science Inventory

Effects-based monitoring and surveillance is increasingly being utilized in conjunction with chemical monitoring to determine potential biological activity associated with environmental contaminants. Supervised approaches targeting specific chemical activity or molecular pathways...

The Molecular Biology of Nitroamine Degradation in Soils

DTIC Science & Technology

2015-07-26

analysis and activity assays .............................................................................. 28 Determination of a putative...81 Figure 52: Specific XplA activity in cells treated with different nitrogen sources. .......... 83 Figure 53: Effect of... activity . Our efforts to develop a functional screen for genes from the soil metagenome were unsuccessful. We developed efficient methods of

Plastics in Our Environment: A Jigsaw Learning Activity

ERIC Educational Resources Information Center

Hampton, Elaine; Wallace, Mary Ann; Lee, Wen-Yee

2009-01-01

In this lesson, a ready-to-teach cooperative reading activity, students learn about the effects of plastics in our environment, specifically that certain petrochemicals act as artificial estrogens and impact hormonal activities. Much of the content in this lesson was synthesized from recent medical research about the impact of xenoestrogens and…

[Interaction of free fatty acids with mitochondria during uncoupling of oxidative phosphorylation].

PubMed

Samartsev, V N; Rybakova, S R; Dubinin, M V

2013-01-01

The activity of free saturated fatty acids (caprylic, capric, lauric, myristic, palmitic and stearic) as inducers and regulators of uncoupling of oxidative phosphorylation with participation of ADP/ATP antiporter, aspartate/glutamate antiporter and cyclosporin A-sensitive structure was investigated in experiments on rat liver mitochondria. It is established that at equal uncoupling activity of fatty acids the regulatory effect is minimal for caprylic acid and raised with increasing the hydrophobicity of fatty acids reaching the maximum value for stearic acid. There exists the linear dependence of the regulatory effect value of fatty acids on fatty acids content in the hydrophobic region of the inner membrane. The model that describes the interaction of fatty acids with the hydrophobic region of the mitochondrial inner membrane preserving functional activity of organelles is developed. It is established that if molecules of various fatty acids being in the hydrophobic region of the membrane are equally effective as uncoupling regulators, their specific uncoupling activity is different. Caprylic acid, a short-chain fatty acid, possesses the highest uncoupling activity. As the acyl chain length increases, the specific uncoupling activity of fatty acids reduces exponentially. Under these conditions components of the uncoupling activity sensitive to glutamate and carboxyatractylate and glutamate and insensitive to these reagents (but sensitive to cyclosporin A) change approximately equally.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

PubMed

Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

2007-12-01

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands.

PubMed

Salter, Jason D; Smith, Harold C

2018-05-23

The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site. We also discuss the effect of APOBEC oligomerization on functionality. Future structural studies will need to address how ssDNA binding away from the active site may enhance catalysis and the mechanism by which RNA binding may modulate catalytic activity on ssDNA. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effects of CO{sub 2} activation on electrochemical performance of microporous carbons derived from poly(vinylidene fluoride)

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

Lee, Seul-Yi; Park, Soo-Jin, E-mail: sjpark@inha.ac.kr

In this work, we have prepared microporous carbons (MPCs) derived from poly(vinylidene fluoride) (PVDF), and the physical activation of MPCs using CO{sub 2} gas is subsequently carried out with various activation temperatures to investigate the electrochemical performance. PVDF is successfully converted into MPCs with a high specific surface area and well-developed micropores. After CO{sub 2} activation, the specific surface areas of MPCs (CA-MPCs) are enhanced by 12% compared with non-activated MPCs. With increasing activation temperature, the micropore size distributions of A-MPCs also become narrower and shift to larger pore size. It is also confirmed that the CO{sub 2} activation hadmore » developed the micropores and introduced the oxygen-containing groups to MPCs′ surfaces. From the results, the specific capacitances of the electrodes in electric double layer capacitors (EDLCs) based on CA-MPCs are distinctly improved through CO{sub 2} activation. The highest specific capacitance of the A-MPCs activated at 700 °C is about 125 F/g, an enhancement of 74% in comparison with NA-MPCs, at a discharge current of 2 A/g in a 6 M KOH electrolyte solution. We also found that micropore size of 0.67 nm has a specific impact on the capacitance behaviors, besides the specific surface area of the electrode samples. - Graphical abstract: The A-MPC samples with high specific surface area (ranging from 1030 to 1082 m{sup 2}/g), corresponding to micropore sizes of 0.67 and 0.72 nm, and with the amount of oxygen-containing groups ranging from 3.2% to 4.4% have been evaluated as electrodes for EDLC applications. . Display Omitted - Highlights: • Microporous carbons (MPCs) were synthesized without activation process. • Next, we carried out the CO{sub 2} activation of MPCs with activation temperatures. • It had developed the micropores and introduced the O-functional groups to MPCs. • The highest specific capacitance: 125 F/g, an increase of 74% compared to MPCs.« less

JT9D-70/59 Improved High Pressure Turbine Active Clearance Control System. [for specific fuel consumption improvement

NASA Technical Reports Server (NTRS)

Gaffin, W. O.

1979-01-01

The JT9D-70/59 high pressure turbine active clearance control system was modified to provide reduction of blade tip clearance when the system is activated during cruise operation. The modification increased the flow capacity and air impingement effectiveness of the cooling air manifold to augment turbine case shrinkage capability, and increased responsiveness of the airseal clearance to case shrinkage. The simulated altitude engine testing indicated a significant improvement in specific fuel consumption with the modified system. A 1000 cycle engine endurance test showed no unusual wear or performance deterioration effects on the engine or the clearance control system. Rig tests indicated that the air impingement and seal support configurations used in the engine tests are near optimum.

Context-specific modulation of cocaine-induced locomotor sensitization and ERK and CREB phosphorylation in rat nucleus accumbens

PubMed Central

Marin, Marcelo T.; Berkow, Alexander; Golden, Sam A.; Koya, Eisuke; Planeta, Cleopatra S.; Hope, Bruce T.

2009-01-01

Learned associations are hypothesized to develop between drug effects and contextual stimuli during repeated drug administration to produce context-specific sensitization that is expressed only in the drug-associated environment and not in a non-drug paired environment. Neuroadaptations that mediate such context-specific behavior are largely unknown. We investigated context-specific modulation of CREB phosphorylation and four upstream kinases in nucleus accumbens that phosphorylate CREB, including ERK, PKA, CaMKII and IV. Rats received seven once daily injections of cocaine or saline in one of two distinct environments outside their home cages. Seven days later, test injections of cocaine or saline were administered in either the Paired or the Non-paired environment. CREB and ERK phosphorylation were assessed with immunohistochemistry while phosphorylation of the remaining kinases, as well as CREB and ERK, were assessed by Western blotting. Repeated cocaine administration produced context-specific sensitized locomotor responses accompanied by context-specific enhancement of the number of cocaine-induced phosphoCREB and phosphoERK immunoreactive nuclei in a minority of neurons. In contrast, CREB and CaMKIV phosphorylation in nucleus accumbens homogenates were decreased by cocaine test injections. We have recently shown that a small number of cocaine-activated accumbens neurons mediate the learned association between cocaine effects and the drug administration environment to produce context-specific sensitization. The corresponding cocaine and context-specific phosphorylation of ERK and CREB in cocaine-activated accumbens neurons in the present study suggests that this signal transduction pathway is also selectively activated in the same set of accumbens neurons. PMID:19912338

Resonant infrared detector with substantially unit quantum efficiency

NASA Technical Reports Server (NTRS)

Farhoomand, Jam (Inventor); Mcmurray, Robert E., Jr. (Inventor)

1994-01-01

A resonant infrared detector includes an infrared-active layer which has first and second parallel faces and which absorbs radiation of a given wavelength. The detector also includes a first tuned reflective layer, disposed opposite the first face of the infrared-active layer, which reflects a specific portion of the radiation incident thereon and allows a specific portion of the incident radiation at the given wavelength to reach the infrared-active layer. A second reflective layer, disposed opposite the second face of the infrared-active layer, reflects back into the infrared-active layer substantially all of the radiation at the given wavelength which passes through the infrared-active layer. The reflective layers have the effect of increasing the quantum efficiency of the infrared detector relative to the quantum efficiency of the infrared-active layer alone.

Optimisation of sewage sludge anaerobic digestion through co-digestion with OFMSW: Effect of collection system and particle size.

PubMed

Silvestre, Gracia; Bonmatí, August; Fernández, Belén

2015-09-01

The effect of organic fraction of municipal solid waste (OFMSW) loading rate and particulate size on the sewage sludge (SS) mesophilic anaerobic co-digestion was assessed in continuous stirred tank reactor at hydraulic retention time of 20days. The SS-OFMSW mixture composed by 54% of the volatile solids fed (inlet-VS), at OLR of 3.1kgCODm(-3)d(-1) (1.9kgVSm(-3)d(-1)), showed the highest increment on the volumetric methane production and yield of +200% and +59% respectively, under stable conditions. The effect of particulate size was assessed with the same mixture and same operational conditions but reducing the OFMSW particulate size from 20mm to 8mm with the aim to improve the hydrolysis step, but the results showed any influence in the OFMSW particulate size range analysed. In addition, specific biomass activity was assessed at the end of each co-digestion period. Results showed that OFMSW promoted β-oxidation syntrophic acetogens and the acetoclastic methanogens activity; although the last increase of the OFMSW percentage (from 47% to 54% inlet-VS) affected negatively the specific substrate activity, but not inhibitory effect was observed. Therefore, the results obtained in the continuous experiment could be related with some inhibitory or toxic effect and not due to hydrolysis limitation. The specific biomass activity test was demonstrated to be an interesting tool to evaluate and control the co-digestion process, especially when conventional parameters did not explain the behaviour of the biological system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control.

PubMed

Christakou, Anastasia; Halari, Rozmin; Smith, Anna B; Ifkovits, Eve; Brammer, Mick; Rubia, Katya

2009-10-15

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

The relative health benefits of different sexual activities.

PubMed

Brody, Stuart

2010-04-01

Although many studies examine purported risks associated with sexual activities, few examine potential physical and mental health benefits, and even fewer incorporate the scientifically essential differentiation of specific sexual behaviors. This review provides an overview of studies examining potential health benefits of various sexual activities, with a focus on the effects of different sexual activities. Review of peer-reviewed literature. Findings on the associations between distinct sexual activities and various indices of psychological and physical function. A wide range of better psychological and physiological health indices are associated specifically with penile-vaginal intercourse. Other sexual activities have weaker, no, or (in the cases of masturbation and anal intercourse) inverse associations with health indices. Condom use appears to impair some benefits of penile-vaginal intercourse. Only a few of the research designs allow for causal inferences. The health benefits associated with specifically penile-vaginal intercourse should inform a new evidence-based approach to sexual medicine, sex education, and a broad range of medical and psychological consultations.

Factors affecting the activity of guanylate cyclase in lysates of human blood platelets.

PubMed Central

Adams, A F; Haslam, R J

1978-01-01

1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by contaminating soluble enzyme, suggesting that physiological aggregating agents may increase cyclic GMP in intact platelets through the effects of intermediary factors. The activated and inhibited states of the enzyme described in the present paper may be relevant to the actions of these factors. PMID:29607

Factors affecting the activity of guanylate cyclase in lysates of human blood platelets.

PubMed

Adams, A F; Haslam, R J

1978-07-15

1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by contaminating soluble enzyme, suggesting that physiological aggregating agents may increase cyclic GMP in intact platelets through the effects of intermediary factors. The activated and inhibited states of the enzyme described in the present paper may be relevant to the actions of these factors.

Peroxisome Proliferator-Activated Receptor-γ Ligands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System

PubMed Central

Carter, Jennifer C.; Church, Frank C.

2011-01-01

We investigated peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands effect on cell motility and the plasminogen activator system using normal MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound-induced migration and chemotaxis. However, the effect was not reversed with pretreatment of cells with the PPAR-γ-specific antagonist GW9662. Immunoblot analysis of conditioned media showed ciglitazone decreased plasminogen activator inhibitor-1 (PAI-1) in both cell lines; this effect was also unaltered by PPAR-γ antagonism. Alternatively, treatment with the ω-6 fatty acid arachidonic acid (ArA), but not the ω-3 fatty acid docosahexanoic acid, increased both MCF-10A cell migration and cell surface uPA activity. Pretreatment with a PPAR-γ antagonist reversed these effects, suggesting that ArA mediates its effect on cell motility and uPA activity through PPAR-γ activation. Collectively, the data suggest PPAR-γ ligands have a differential effect on normal and malignant cell migration and the plasminogen activation system, resulting from PPAR-γ-dependent and PPAR-γ-independent effects. PMID:22131991

Reduced Alzheimer’s disease pathology by St. John’s wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice

PubMed Central

Hofrichter, Jacqueline; Krohn, Markus; Schumacher, Toni; Lange, Cathleen; Feistel, Björn; Walbroel, Bernd; Heinze, Hans-Jochen; Crockett, Sara; Sharbel, Timothy F.; Pahnke, Jens

2013-01-01

Soluble β-amyloid peptides (Aβ) and small Aβ oligomers represent the most toxic peptide moieties recognized in brains affected by Alzheimer’s disease (AD). Here we provide the first evidence that specific St. John’s wort (SJW) extracts both attenuate Aβ-induced histopathology and alleviate memory impairments in APP-transgenic mice. Importantly, these effects are attained independently of hyperforin. Specifically, two extracts characterized by low hyperforin content (i) significantly decrease intracerebral Aβ42 levels, (ii) decrease the number and size of amyloid plaques, (iii) rescue neocortical neurons, (iv) restore cognition to normal levels, and (iv) activate microglia in vitro and in vivo. Mechanistically, we reveal that the reduction of soluble Aβ42 species is the consequence of a highly increased export activity in the blood-brain barrier ABCC1 transporter, which was found to play a fundamental role in Aβ excretion into the bloodstream. These data (i) support the significant beneficial potential of SJW extracts on AD proteopathy, and (ii) demonstrate for the first time that hyperforin concentration does not necessarily correlate with their therapeutic effects. Hence, by activating ABC transporters, specific extracts of SJW may be used to treat AD and other diseases involving peptide accumulation and cognition impairment. We propose that the anti-depressant and anti-dementia effects of these hyperforin-reduced phytoextracts could be combined for treatment of the elderly, with a concomitant reduction in deleterious hyperforin-related side effects. PMID:24156265

Reduced Alzheimer's disease pathology by St. John's Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice.

PubMed

Hofrichter, Jacqueline; Krohn, Markus; Schumacher, Toni; Lange, Cathleen; Feistel, Björn; Walbroel, Bernd; Heinze, Hans-Jochen; Crockett, Sara; Sharbel, Timothy F; Pahnke, Jens

2013-12-01

Soluble β-amyloid peptides (Aβ) and small Aβ oligomers represent the most toxic peptide moieties recognized in brains affected by Alzheimer's disease (AD). Here we provide the first evidence that specific St. John's wort (SJW) extracts both attenuate Aβ-induced histopathology and alleviate memory impairments in APP-transgenic mice. Importantly, these effects are attained independently of hyperforin. Specifically, two extracts characterized by low hyperforin content (i) significantly decrease intracerebral Aβ42 levels, (ii) decrease the number and size of amyloid plaques, (iii) rescue neocortical neurons, (iv) restore cognition to normal levels, and (iv) activate microglia in vitro and in vivo. Mechanistically, we reveal that the reduction of soluble Aβ42 species is the consequence of a highly increased export activity in the bloodbrain barrier ABCC1transporter, which was found to play a fundamental role in Aβ excretion into the bloodstream. These data (i) support the significant beneficial potential of SJW extracts on AD proteopathy, and (ii) demonstrate for the first time that hyperforin concentration does not necessarily correlate with their therapeutic effects. Hence, by activating ABC transporters, specific extracts of SJW may be used to treat AD and other diseases involving peptide accumulation and cognition impairment. We propose that the anti-depressant and anti-dementia effects of these hyperforin-reduced phytoextracts could be combined for treatment of the elderly, with a concomitant reduction in deleterious hyperforin-related side effects.

Health risk assessment of potable water containing small amount of tritium oxide

NASA Astrophysics Data System (ADS)

Momot, O. A.; Synzynys, B. I.; Oudalova, A. A.

2017-01-01

The problem of groundwater pollution with tritium in a vicinity of radiation-dangerous facilities in Obninsk is considered. The information on the specific activity of tritium in Obninsk water sources is provided. The formula for the calculation of the β-radiation absorbed dose from tritium ingestion is proposed, reflecting the biological behavior of tritium in a human body. To establish the extent of tritium effects on human, the health risk is assessed. It is shown that if the specific activity of tritium in drinking water amounts to 10 Bq/l, the risk of stochastic effects of radiation will not exceed the limit of the individual lifetime risk.

Temporal Dynamics of Activation of Thematic and Functional Knowledge During Conceptual Processing of Manipulable Artifacts

PubMed Central

Kalénine, Solène; Mirman, Daniel; Middleton, Erica L.; Buxbaum, Laurel J.

2012-01-01

The current research aimed at specifying the activation time course of different types of semantic information during object conceptual processing and the effect of context on this time course. We distinguished between thematic and functional knowledge and the specificity of functional similarity. Two experiments were conducted with healthy older adults using eye tracking in a word-to-picture matching task. The time course of gaze fixations was used to assess activation of distractor objects during the identification of manipulable artifact targets (e.g., broom). Distractors were (a) thematically related (e.g., dustpan), (b) related by a specific function (e.g., vacuum cleaner), or (c) related by a general function (e.g., sponge). Growth curve analyses were used to assess competition effects when target words were presented in isolation (Experiment 1) and embedded in contextual sentences of different generality levels (Experiment 2). In the absence of context, there was earlier and shorter lasting activation of thematically related as compared to functionally related objects. The time course difference was more pronounced for general functions than specific functions. When contexts were provided, functional similarities that were congruent with context generality level increased in salience with earlier activation of those objects. Context had little impact on thematic activation time course. These data demonstrate that processing a single manipulable artifact concept implicitly activates thematic and functional knowledge with different time courses and that context speeds activation of context-congruent functional similarity. PMID:22449134

Substrate specificity effects of lipoxygenase products and inhibitors on soybean lipoxygenase-1.

PubMed

Wecksler, Aaron T; Garcia, Natalie K; Holman, Theodore R

2009-09-15

Recently, it has been shown that lipoxygenase (LO) products affect the substrate specificity of human 15-LO. In the current paper, we demonstrate that soybean LO-1 (sLO-1) is not affected by its own products, however, inhibitors which bind the allosteric site, oleyl sulfate (OS) and palmitoleyl sulfate (PS), not only lower catalytic activity, but also change the substrate specificity, by increasing the arachidonic acid (AA)/linoleic acid (LA) ratio to 4.8 and 4.0, respectively. The fact that LO inhibitors can lower activity and also change the LO product ratio is a new concept in lipoxygenase inhibition, where the goal is to not only reduce the catalytic activity but also alter substrate selectivity towards a physiologically beneficial product.

Effectiveness of Cultural Adaptations of Interventions Aimed at Smoking Cessation, Diet, and/or Physical Activity in Ethnic Minorities. A Systematic Review

PubMed Central

Nierkens, Vera; Hartman, Marieke A.; Nicolaou, Mary; Vissenberg, Charlotte; Beune, Erik J. A. J.; Hosper, Karen; van Valkengoed, Irene G.; Stronks, Karien

2013-01-01

Background The importance of cultural adaptations in behavioral interventions targeting ethnic minorities in high-income societies is widely recognized. Little is known, however, about the effectiveness of specific cultural adaptations in such interventions. Aim To systematically review the effectiveness of specific cultural adaptations in interventions that target smoking cessation, diet, and/or physical activity and to explore features of such adaptations that may account for their effectiveness. Methods Systematic review using MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials registers (1997–2009). Inclusion criteria: a) effectiveness study of a lifestyle intervention targeted to ethnic minority populations living in a high income society; b) interventions included cultural adaptations and a control group that was exposed to the intervention without the cultural adaptation under study; c) primary outcome measures included smoking cessation, diet, or physical activity. Results Out of 44904 hits, we identified 17 studies, all conducted in the United States. In five studies, specific cultural adaptations had a statistically significant effect on primary outcomes. The remaining studies showed no significant effects on primary outcomes, but some presented trends favorable for cultural adaptations. We observed that interventions incorporating a package of cultural adaptations, cultural adaptations that implied higher intensity and those incorporating family values were more likely to report statistically significant effects. Adaptations in smoking cessation interventions seem to be more effective than adaptations in interventions aimed at diet and physical activity. Conclusion This review indicates that culturally targeted behavioral interventions may be more effective if cultural adaptations are implemented as a package of adaptations, the adaptation includes family level, and where the adaptation results in a higher intensity of the intervention. More systematic experiments are needed in which the aim is to gain insight in the best mix of cultural adaptations among diverse populations in various settings, particularly outside the US. PMID:24116000

Effectiveness of cultural adaptations of interventions aimed at smoking cessation, diet, and/or physical activity in ethnic minorities. a systematic review.

PubMed

Nierkens, Vera; Hartman, Marieke A; Nicolaou, Mary; Vissenberg, Charlotte; Beune, Erik J A J; Hosper, Karen; van Valkengoed, Irene G; Stronks, Karien

2013-01-01

The importance of cultural adaptations in behavioral interventions targeting ethnic minorities in high-income societies is widely recognized. Little is known, however, about the effectiveness of specific cultural adaptations in such interventions. To systematically review the effectiveness of specific cultural adaptations in interventions that target smoking cessation, diet, and/or physical activity and to explore features of such adaptations that may account for their effectiveness. Systematic review using MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials registers (1997-2009). a) effectiveness study of a lifestyle intervention targeted to ethnic minority populations living in a high income society; b) interventions included cultural adaptations and a control group that was exposed to the intervention without the cultural adaptation under study; c) primary outcome measures included smoking cessation, diet, or physical activity. Out of 44904 hits, we identified 17 studies, all conducted in the United States. In five studies, specific cultural adaptations had a statistically significant effect on primary outcomes. The remaining studies showed no significant effects on primary outcomes, but some presented trends favorable for cultural adaptations. We observed that interventions incorporating a package of cultural adaptations, cultural adaptations that implied higher intensity and those incorporating family values were more likely to report statistically significant effects. Adaptations in smoking cessation interventions seem to be more effective than adaptations in interventions aimed at diet and physical activity. This review indicates that culturally targeted behavioral interventions may be more effective if cultural adaptations are implemented as a package of adaptations, the adaptation includes family level, and where the adaptation results in a higher intensity of the intervention. More systematic experiments are needed in which the aim is to gain insight in the best mix of cultural adaptations among diverse populations in various settings, particularly outside the US.

Gene–Physical Activity Interactions: Overview of Human Studies

PubMed Central

Rankinen, Tuomo; Bouchard, Claude

2009-01-01

Physical activity level is an important component of the total daily energy expenditure and as such contributes to body weight regulation. A body of data indicates that the level of physical activity plays a role in the risk of excessive weight gain, in weight loss programs, and particularly in the prevention of weight regain. Most studies dealing with potential gene–physical activity interaction effects use an exercise and fitness or performance paradigm as opposed to an obesity-driven model. From these studies, it is clear that there are considerable individual differences in the response to an exercise regimen and that there is a substantial familial aggregation component to the observed heterogeneity. Few studies have focused on the role of specific genes in accounting for the highly prevalent gene–exercise interaction effects. Results for specific genes have been inconsistent with few exceptions. Progress is likely to come when studies will be designed to truly address gene–exercise or physical activity interaction issues and with sample sizes that will provide adequate statistical power. PMID:19037212

Active music classes in infancy enhance musical, communicative and social development.

PubMed

Gerry, David; Unrau, Andrea; Trainor, Laurel J

2012-05-01

Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random assignment to 6 months of active participatory musical experience beginning at 6 months of age accelerates acquisition of culture-specific knowledge of Western tonality in comparison to a similar amount of passive exposure to music. Furthermore, infants assigned to the active musical experience showed superior development of prelinguistic communicative gestures and social behaviour compared to infants assigned to the passive musical experience. These results indicate that (1) infants can engage in meaningful musical training when appropriate pedagogical approaches are used, (2) active musical participation in infancy enhances culture-specific musical acquisition, and (3) active musical participation in infancy impacts social and communication development. © 2012 Blackwell Publishing Ltd.

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

PubMed

Farahati, J; Bier, D; Scheubeck, M; Lassmann, M; Schelper, L F; Grelle, I; Hanscheid, H; Biko, J; Graefe, K H; Reiners, C

1997-03-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Effect of specific activity on organ uptake of iodine-123-meta-iodobenzylguanidine in humans.

PubMed

Farahati, J; Lassmann, M; Scheubeck, M; Bier, D; Hanscheid, H; Schelper, L; Grelle, I; Biko, J; Werner, E; Graefe, K; Reiners, C

1997-04-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activity on organ uptake of radioiodinated MIBG. the kinetics of no-carrier-added (n.c.a.) [I-123]MIBG (greater than or equal to 7.4 TBq/mu mol) were compared with those of commercial (com.) [I-123]MIBG (similar to 74 MBq/mu mol) in 3 healthy volunteers by serial imaging and blood sampling. The organ uptake of radioiodinated MIBG did not remarkably differ between the two specific activities. Due to rapid degradation a more pronounced accumulation of radioactivity was present in plasma alter n.c.a. than after com. [I-123]MIBG resulting in a higher background and thyroid activity. In addition due to a prolonged residence time of the radioactivity, the radiation exposure to organs was in general slightly higher with n.c.a. [I-123]MIBG as compared to com. [I-123]MIBG. This finding highlights the higher in vivo deiodination of n.c.a. [I-123]MIBG than of com. [I-123]MIBG in humans. In the treatment of children suffering from neuroblastoma, therefore, degradation of n.c.a. [I-123]MIBG may decrease the concentration of radioiodinated MIBG available for binding at tumor sites and result in higher radiation exposure of non-tumor tissue.

Repurposing Ospemifene for Potentiating an Antigen-Specific Immune Response

PubMed Central

Kao, Chiao-Jung; Wurz, Gregory T.; Lin, Yi-Chen; Vang, Daniel P.; Phong, Brian; DeGregorio, Michael W.

2016-01-01

Objective Ospemifene, an estrogen receptor agonist/antagonist approved for treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. Methods Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo. The effects of ospemifene (OSP) on the immune response to a peptide cancer vaccine (PV) were evaluated following chronic [control (n=22); OSP 50 mg/kg (n=16); PV (n=6); OSP+PV (n=11)], intermittent [control (n=10); OSP 10 and 50 mg/kg (n=11); PV (n=11); combination treatment (n=11 each dose)] and pretreatment [control; OSP 100 mg/kg; PV 100 µg; combination treatment (n=8 all groups)] ospemifene oral dosing schedules in a total of 317 mixed-sex tumor-bearing and non-tumor-bearing mice. Results The results showed that ospemifene induced expression of the key TH1 cytokines interferon gamma and interleukin-2 in vitro, which may be mediated by stimulating T cells through phosphoinositide 3-kinase and calmodulin signaling pathways. In combination with an antigen-specific peptide cancer vaccine, ospemifene increased antigen-specific immune response and increased cytotoxic T-lymphocyte activity in tumor-bearing and non-tumor-bearing mice. The pretreatment, intermittent, and chronic dosing schedules of ospemifene activate naïve T cells, modulate antigen-induced tolerance and reduce tumor-associated, pro-inflammatory cytokines, respectively. Conclusions Taken together, ospemifene’s dose response and schedule-dependent immune modulating activity offers a method of tailoring and augmenting the efficacy of previously failed antigen-specific cancer vaccines for a wide range of malignancies. PMID:27922937

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

PubMed

Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

2017-12-11

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

A gene regulatory network armature for T-lymphocyte specification

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

Fung, Elizabeth-sharon

Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through whichmore » T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.« less

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

PubMed

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-03-19

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

PubMed Central

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Endocrine-Active Pharmaceuticals: An Environmental Concern?

EPA Science Inventory

Recently, there has been growing interest in pharmaceuticals that are specifically designed to have endocrine activity, such as the estrogens used in birth control pills, exerting unintended effects on fish and other aquatic organisms. These pharmaceuticals may not be persistent...

Cytokinin oxidase from Phaseolus vulgaris callus tissues. Enhanced in vitro activity of the enzyme in the presence of copper-imidazole complexes

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

Chatfield, J.M.; Armstrong, D.J.

1987-07-01

The effects of metal ions on cytokinin oxidase activity extracted from callus tissues of Phaseolus vulgaris L. cv Great Northern have been examined using an assay based on the oxidation of N/sup 6/-(..delta../sup 2/-isopentenyl)-adenine-2,8-/sup 3/H (i/sup 6/ Ade) to adenine (Ade). The addition of cupric ions to reaction mixtures containing imidazole buffer markedly enhanced cytokinin oxidase activity. In the presence of optimal concentrations of copper and imidazole, cytokinin oxidase activity was stimulated more than 20-fold. The effect was enzyme dependent, specific for copper, and observed only in the presence of imidazole. The substrate specificity of the copper-imidazole enhanced reaction, asmore » judged by substrate competition tests, was the same as that observed in the absence of copper and imidazole. Similarly, in tests involving DEAE-cellulose chromatography, elution profiles of cytokinin oxidase activity determined using a copper-imidazole enhanced assay were identical to those obtained using an assay without copper and imidazole. On the basis of these results, the addition of copper and imidazole to reaction mixtures used to assay for cytokinin oxidase activity is judged to provide a reliable and specific assay of greatly enhanced sensitivity for the enzyme. The mechanism by which copper and imidazole enhance cytokinin oxidase activity is not certain, but the reaction catalyzed by the enzyme was not inhibited by anaerobic conditions when these reagents were present. This observation suggests that copper-imidazole complexes are substituting for oxygen in the reaction mechanism by which cytokinin oxidase effects cleavage of the N/sup 6/-side chain of i/sup 6/ Ade.« less

Distinct Olfactory Cross-Modal Effects on the Human Motor System

PubMed Central

Rossi, Simone; De Capua, Alberto; Pasqualetti, Patrizio; Ulivelli, Monica; Falzarano, Vincenzo; Bartalini, Sabina; Passero, Stefano; Nuti, Daniele

2008-01-01

Background Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. Methodology/Principal Findings In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. Conclusions/Significance Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications. PMID:18301777

Corn stalks char from fast pyrolysis as precursor material for preparation of activated carbon in fluidized bed reactor.

PubMed

Wang, Zhiqi; Wu, Jingli; He, Tao; Wu, Jinhu

2014-09-01

Corn stalks char from fast pyrolysis was activated by physical and chemical activation process in a fluidized bed reactor. The structure and morphology of the carbons were characterized by N2 adsorption and SEM. Effects of activation time and activation agents on the structure of activation carbon were investigated. The physically activated carbons with CO2 have BET specific surface area up to 880 m(2)/g, and exhibit microporous structure. The chemically activated carbons with H3PO4 have BET specific surface area up to 600 m(2)/g, and exhibit mesoporous structure. The surface morphology shows that physically activated carbons exhibit fibrous like structure in nature with long ridges, resembling parallel lines. Whereas chemically activated carbons have cross-interconnected smooth open pores without the fibrous like structure. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Brief Report: The Effects of Equine-Assisted Activities on the Social Functioning in Children and Adolescents with Autism Spectrum Disorder.

PubMed

Anderson, Sophie; Meints, Kerstin

2016-10-01

Equine-assisted activities and therapies are increasing in popularity for treatment of ASD symptoms. This research evaluated effects of a 5-week programme of therapeutic riding on social functioning of children/adolescents (N = 15) with ASD. The effectiveness of the programme was evaluated using the autism spectrum quotient, the Vineland Adaptive Behaviour Scale and the empathising and systemising quotient. Results established that the TR intervention increased empathising and reduced maladaptive behaviours. The findings also indicated that specific adaptive behaviours like socialization and communication were not affected by the intervention. Thus, a complex picture of the effects of this intervention emerges: while TR does not change all of the child's behaviour, it can improve specific aspects of social functioning and also reduce maladaptive ASD traits.

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

PubMed Central

Wang, Haibo; Hartnett, M. Elizabeth

2017-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis. PMID:28587189

Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes

PubMed Central

Madhusudhan, Thati; Wang, Hongjie; Straub, Beate K.; Gröne, Elisabeth; Zhou, Qianxing; Shahzad, Khurrum; Müller-Krebs, Sandra; Schwenger, Vedat; Gerlitz, Bruce; Grinnell, Brian W.; Griffin, John H.; Reiser, Jochen; Gröne, Hermann-Josef; Esmon, Charles T.; Nawroth, Peter P.

2012-01-01

The cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a protease-activated receptor-1 (PAR-1) and endothelial protein C receptor-dependent mechanism. Conversely, the signaling mechanism through which aPC protects podocytes remains unknown. While exploring the latter, we identified a novel aPC/PAR-dependent cytoprotective signaling mechanism. In podocytes, aPC inhibits apoptosis through proteolytic activation of PAR-3 independent of endothelial protein C receptor. PAR-3 is not signaling competent itself as it requires aPCinduced heterodimerization with PAR-2 (human podocytes) or PAR-1 (mouse podocytes). This cytoprotective signaling mechanism depends on caveolin-1 dephosphorylation. In vivo aPC protects against lipopolysaccharide-induced podocyte injury and proteinuria. Genetic deletion of PAR-3 impairs the nephroprotective effect of aPC, demonstrating the crucial role of PAR-3 for aPC-dependent podocyte protection. This novel, aPC-mediated interaction of PARs demonstrates the plasticity and cell-specificity of cytoprotective aPC signaling. The evidence of specific, dynamic signaling complexes underlying aPC-mediated cytoprotection may allow the design of cell type specific targeted therapies. PMID:22117049

Soil ecosystem functioning under climate change: plant species and community effects

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

Kardol, Paul; Cregger, Melissa; Campany, Courtney E

2010-01-01

Feedbacks of terrestrial ecosystems to climate change depend on soil ecosystem dynamics. Soil ecosystems can directly and indirectly respond to climate change. For example, warming directly alters microbial communities by increasing their activity. Climate change may also alter plant community composition, thus indirectly altering the microbial communities that feed on their inputs. To better understand how climate change may directly and indirectly alter soil ecosystem functioning, we investigated old-field plant community and soil ecosystem responses to single and combined effects of elevated [CO2], warming, and water availability. Specifically, we collected soils at the plot level (plant community soils), and beneathmore » dominant plant species (plant-specific soils). We used microbial enzyme activities and soil nematodes as indicators for soil ecosystem functioning. Our study resulted in two main findings: 1) Overall, while there were some interactions, water, relative to increases in [CO2] and warming, had the largest impact on plant community composition, soil enzyme activities, and soil nematodes. Multiple climate change factors can interact to shape ecosystems, but in this case, those interactions were largely driven by changes in water availability. 2) Indirect effects of climate change, via changes in plant communities, had a significant impact on soil ecosystem functioning and this impact was not obvious when looking at plant community soils. Climate change effects on enzyme activities and soil nematode abundance and community structure strongly differed between plant community soils and plant-specific soils, but also within plant-specific soils. In sum, these results indicate that accurate assessments of climate change impacts on soil ecosystem functioning require incorporating the concurrent changes in plant function and plant community composition. Climate change-induced shifts in plant community composition will likely modify or counteract the direct impact of climate change on soil ecosystem functioning, and hence, these indirect effects should be taken into account when predicting how climate change will alter ecosystem functioning.« less

Soil ecosystem functioning under climate change: plant species and community effects.

PubMed

Kardol, Paul; Cregger, Melissa A; Campany, Courtney E; Classen, Aimee T

2010-03-01

Feedbacks of terrestrial ecosystems to atmospheric and climate change depend on soil ecosystem dynamics. Soil ecosystems can directly and indirectly respond to climate change. For example, warming directly alters microbial communities by increasing their activity. Climate change may also alter plant community composition, thus indirectly altering the soil communities that depend on their inputs. To better understand how climate change may directly and indirectly alter soil ecosystem functioning, we investigated old-field plant community and soil ecosystem responses to single and combined effects of elevated [CO2], warming, and precipitation in Tennessee (USA). Specifically, we collected soils at the plot level (plant community soils) and beneath dominant plant species (plant-specific soils). We used microbial enzyme activities and soil nematodes as indicators for soil ecosystem functioning. Our study resulted in two main findings: (1) Overall, while there were some interactions, water, relative to increases in [CO2] and warming, had the largest impact on plant community composition, soil enzyme activity, and soil nematodes. Multiple climate-change factors can interact to shape ecosystems, but in our study, those interactions were largely driven by changes in water. (2) Indirect effects of climate change, via changes in plant communities, had a significant impact on soil ecosystem functioning, and this impact was not obvious when looking at plant community soils. Climate-change effects on enzyme activities and soil nematode abundance and community structure strongly differed between plant community soils and plant-specific soils, but also within plant-specific soils. These results indicate that accurate assessments of climate-change impacts on soil ecosystem functioning require incorporating the concurrent changes in plant function and plant community composition. Climate-change-induced shifts in plant community composition will likely modify or counteract the direct impact of atmospheric and climate change on soil ecosystem functioning, and hence, these indirect effects should be taken into account when predicting the manner in which global change will alter ecosystem functioning.

Different roles of protein kinase C alpha and delta isoforms in the regulation of neutral sphingomyelinase activity in HL-60 cells.

PubMed Central

Visnjić, D; Batinić, D; Banfić, H

1999-01-01

The signalling mechanisms responsible for the hydrolysis of sphingomyelin mediated by 1,25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3)] and interferon gamma (IFN-gamma) in HL-60 cells were investigated. IFN-gamma was found to increase selectively the activity of cytosolic, Mg(2+)-independent, neutral sphingomyelinase. The treatment of HL-60 cells with the combination of 1,25(OH)(2)D(3) and IFN-gamma had an additive effect on sphingomyelin hydrolysis, ceramide release and the activity of cytosolic, Mg(2+)-independent, neutral sphingomyelinase. The pretreatment of HL-60 cells with staurosporine, chelerythrine chloride and bisindolylmaleimide abolished the activity of sphingomyelinase in response to 1,25(OH)(2)D(3) and IFN-gamma. Calphostin C, which acts on the regulatory site of protein kinase C (PKC), and Gö 6976, a selective inhibitor of Ca(2+)-dependent PKC isoforms, inhibited the effect of 1,25(OH)(2)D(3) but had no effect on the IFN-gamma-mediated increase in activity of sphingomyelinase. Isoform-specific antibodies were used to deplete different PKC isoforms from cytosol before the treatment of the cytosolic fraction with 1,25(OH)(2)D(3), arachidonic acid (AA) and PMA. The depletion of PKC isoforms beta(1), beta(2), epsilon, eta, mu, zeta and lambda had no effect on the activation of sphingomyelinase induced by 1,25(OH)(2)D(3) or by AA. The depletion of PKC alpha from the cytosol completely abolished the effect of 1,25(OH)(2)D(3) on sphingomyelinase activity but had no effect on the AA-induced activity of sphingomyelinase. PMA had no effect on the activity of sphingomyelinase in either untreated or alpha-depleted cytosol but significantly increased the activity of sphingomyelinase when added to cytosol depleted of PKC delta. Moreover, PMA inhibited the effect of 1,25(OH)(2)D(3) on sphingomyelinase activation but the inhibitory effect was abolished by prior depletion of PKC delta from the cytosol. These studies demonstrate that 1,25(OH)(2)D(3)-induced activation of sphingomyelinase is mediated by PKC alpha. Furthermore, PKC delta had an inhibitory effect on sphingomyelinase, suggesting that the difference between the 1,25(OH)(2)D(3)- and PMA-mediated effects on sphingomyelin turnover depends on the specific regulation of the PKC alpha and PKC delta isoforms. PMID:10585882

The Impact of Physical Activity and Obesity on Academic Achievement among Elementary Students

ERIC Educational Resources Information Center

Byrd, Jimmy

2007-01-01

This study compared the effect of physical activity and obesity on academic achievement and was based on the premise that the health of a child has an effect on his or her ability to learn and to achieve academically. Specifically, health-related topics of inactivity and obesity were considered. The participants included 12,607 third grade…

The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves

PubMed Central

Balser, Nils; Lorey, Britta; Pilgramm, Sebastian; Naumann, Tim; Kindermann, Stefan; Stark, Rudolf; Zentgraf, Karen; Williams, A. Mark; Munzert, Jörn

2014-01-01

In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action–observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task-specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task. PMID:25136305

Assessment of Annual Effective Dose for Natural Radioactivity of Gamma Emitters in Biscuit Samples in Iraq.

PubMed

Abojassim, Ali Abid; Al-Alasadi, Lubna A; Shitake, Ahmed R; Al-Tememie, Faeq A; Husain, Afnan A

2015-09-01

Biscuits are an important type of food, widely consumed by babies in Iraq and other countries. This work uses gamma spectroscopy to measure the natural radioactivity due to long-lived gamma emitters in children's biscuits; it also estimates radiation hazard indices, that is, the radium equivalent activity, the representative of gamma level index, the internal hazard index, and the annual effective dose in children. Ten samples were collected from the Iraqi market from different countries of origin. The average specific activities for (226)Ra, (232)Th, and (40)K were 9.390, 3.1213, and 214.969 Bq/kg, respectively, but the average of the radium equivalent activity and the internal hazard index were 33.101 Bq/kg and 0.107, respectively. The total average annual effective dose from consumption by adults, children, and infants is estimated to be 0.655, 1.009, and 0.875 mSv, respectively. The values found for specific activity, radiation hazard indices, and annual effective dose in all samples in this study were lower than worldwide median values for all groups; therefore, these values are found to be safe.

Effects of aripiprazole and haloperidol on neural activation during a simple motor task in healthy individuals: A functional MRI study.

PubMed

Goozee, Rhianna; O'Daly, Owen; Handley, Rowena; Reis Marques, Tiago; Taylor, Heather; McQueen, Grant; Hubbard, Kathryn; Pariante, Carmine; Mondelli, Valeria; Reinders, Antje A T S; Dazzan, Paola

2017-04-01

The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators

PubMed Central

Polstein, Lauren R.; Perez-Pinera, Pablo; Kocak, D. Dewran; Vockley, Christopher M.; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E.; Reddy, Timothy E.; Gersbach, Charles A.

2015-01-01

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. PMID:26025803

Influence of Tridax procumbens on lysyl oxidase activity and wound healing.

PubMed

Udupa, S L; Udupa, A L; Kulkarni, D R

1991-08-01

The effects of an indigenous drug, Tridax procumbens L. (Compositae), on developing granulation tissue in rats were studied. Subcutaneously harvested granuloma tissue formed on dead space wound was removed at 4 day intervals up to 32 days of wounding. Lysyl oxidase activity, protein content, specific activity, and breaking strength were all increased in drug-treated animals as compared to controls. A fall in the lysyl oxidase activity was observed in drug-treated animals after day 8. The drug may be having a dual role: one a stimulatory (direct) effect in the initial phase of wound healing and the other a depressant (indirect) effect in the later stage.

Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

PubMed Central

Mattsson, Johanna M.; Ravela, Suvi; Hekim, Can; Jonsson, Magnus; Malm, Johan; Närvänen, Ale; Stenman, Ulf-Håkan; Koistinen, Hannu

2014-01-01

Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. PMID:25237904

Investigating Commercial Cellulase Performances Toward Specific Biomass Recalcitrance Factors Using Reference Substrates

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

Ju, Xiaohui; Bowden, Mark E.; Engelhard, Mark H.

Three commercial cellulase preparations, Novozymes Cellic® Ctec2, Dupont Accellerase® 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulose enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulose performance. While the degree of polymerization of cellulose in the reference substrates didmore » not present a major recalcitrance factor to Novozymes Cellic® Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.« less

Investigating commercial cellulase performances toward specific biomass recalcitrance factors using reference substrates.

PubMed

Ju, Xiaohui; Bowden, Mark; Engelhard, Mark; Zhang, Xiao

2014-05-01

Three commercial cellulase preparations, Novozymes Cellic(®) Ctec2, Dupont Accellerase(®) 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulase enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulase performance. While the degree of polymerization of cellulose in the reference substrates did not present a major recalcitrance factor to Novozymes Cellic(®) Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.

Rational Quantitative Structure-Activity Relationship (RQSAR) Screen for PXR and CAR Isoform-Specific Nuclear Receptor Ligands

PubMed Central

Dring, Ann M.; Anderson, Linnea E.; Qamar, Saima; Stoner, Matthew A.

2010-01-01

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits. Multiple CAR isoforms have been detected in human liver, with the most abundant being the constitutively active reference, CAR1, and the ligand-dependent isoform CAR3. It has been assumed that any compound that binds CAR1 should also activate CAR3, and so CAR3 can be used as a ligand-activated surrogate for CAR1 studies. The possibility of CAR3-specific ligands has not, so far, been addressed. To investigate the differences between CAR1, CAR3 and PXR, and to look for more CAR ligands that may be of use in quantitative structure-activity relationship (QSAR) studies, we performed a luciferase transactivation assay screen of 60 mostly non-steroid compounds. Known active compounds with different core chemistries were chosen as starting points and structural variants were rationally selected for screening. Distinct differences in agonist versus inverse agonist/antagonist effects were seen in 49 compounds that had some ligand effect on at least one receptor and 18 that had effects on all three receptors; eight were CAR1 ligands only, three were CAR3 only ligands and four affected PXR only. This work provides evidence for new CAR ligands, some of which have CAR3-specific effects, and provides observational data on CAR and PXR ligands with which to inform in silico strategies. Compounds that demonstrated unique activity on any one receptor are potentially valuable diagnostic tools for the investigation of in vivo molecular targets. PMID:20869355

Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation

PubMed Central

Yunn, Na-Oh; Koh, Ara; Han, Seungmin; Lim, Jong Hun; Park, Sehoon; Lee, Jiyoun; Kim, Eui; Jang, Sung Key; Berggren, Per-Olof; Ryu, Sung Ho

2015-01-01

Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors. PMID:26245346

Web addiction in the brain: Cortical oscillations, autonomic activity, and behavioral measures.

PubMed

Balconi, Michela; Campanella, Salvatore; Finocchiaro, Roberta

2017-09-01

Background and aims Internet addiction (IA) was recently defined as a disorder tagging both the impulse control and the reward systems. Specifically, inhibitory deficits and reward bias were considered highly relevant in IA. This research aims to examine the electrophysiological correlates and autonomic activity [skin conductance response (SCR) and heart rate] in two groups of young subjects (N = 25), with high or low IA profile [tested by the Internet Addiction Test (IAT)], with specific reference to gambling behavior. Methods Oscillatory brain activity (delta, theta, alpha, beta, and gamma) and autonomic and behavioral measures [response times (RTs) and error rates (ERs)] were acquired during the performance of a Go/NoGo task in response to high-rewarding (online gambling videos and video games) or neutral stimuli. Results A better performance (reduced ERs and reduced RTs) was revealed for high IAT in the case of NoGo trials representing rewarding cues (inhibitory control condition), probably due to a "gain effect" induced by the rewarding condition. In addition, we also observed for NoGo trials related to gambling and video games stimuli that (a) increased low-frequency band (delta and theta) and SCR and (b) a specific lateralization effect (more left-side activity) delta and theta in high IAT. Discussion Both inhibitory control deficits and reward bias effect were considered to explain IA.

Transient Receptor Potential Channels as Targets for Phytochemicals

PubMed Central

2015-01-01

To date, 28 mammalian transient receptor potential (TRP) channels have been cloned and characterized. They are grouped into six subfamilies on the basis of their amino acid sequence homology: TRP Ankyrin (TRPA), TRP Canonical (TRPC), TRP Melastatin (TRPM), TRP Mucolipin (TRPML), TRP Polycystin (TRPP), and TRP Vanilloid (TRPV). Most of the TRP channels are nonselective cation channels expressed on the cell membrane and exhibit variable permeability ratios for Ca2+ versus Na+. They mediate sensory functions (such as vision, nociception, taste transduction, temperature sensation, and pheromone signaling) and homeostatic functions (such as divalent cation flux, hormone release, and osmoregulation). Significant progress has been made in our understanding of the specific roles of these TRP channels and their activation mechanisms. In this Review, the emphasis will be on the activation of TRP channels by phytochemicals that are claimed to exert health benefits. Recent findings complement the anecdotal evidence that some of these phytochemicals have specific receptors and the activation of which is responsible for the physiological effects. Now, the targets for these phytochemicals are being unveiled; a specific hypothesis can be proposed and tested experimentally to infer a scientific validity of the claims of the health benefits. The broader and pressing issues that have to be addressed are related to the quantities of the active ingredients in a given preparation, their bioavailability, metabolism, adverse effects, excretion, and systemic versus local effects. PMID:24926802

Effect of nano-scale characteristics of graphene on electrochemical performance of activated carbon supercapacitor electrodes

NASA Astrophysics Data System (ADS)

Jasni, M. R. M.; Deraman, M.; Suleman, M.; Hamdan, E.; Sazali, N. E. S.; Nor, N. S. M.; Shamsudin, S. A.

2016-02-01

Graphene with its typical nano-scale characteristic properties has been widely used as an additive in activated carbon electrodes in order to enhance the performance of the electrodes for their use in high performance supercapacitors. Activated carbon monoliths (ACMs) electrodes have been prepared by carbonization and activation of green monoliths (GMs) of pre-carbonized fibers of oil palm empty fruit bunches or self-adhesive carbon grains (SACGs) and SACGs added with 6 wt% of KOH-treated multi-layer graphene. ACMs electrodes have been assembled in symmetrical supercapacitor cells that employed aqueous KOH electrolyte (6 M). The cells have been tested with cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge discharge methods to investigate the effect of graphene addition on the specific capacitance (Csp), specific energy (E), specific power (P), equivalent series resistance (ESR) and response time (τo) of the supercapacitor cells. The results show that the addition of graphene in the GMs change the values of Csp, Emax, Pmax, ESR and τo from (61-96) F/g, 2 Wh/kg, 104 W/kg, 2.6 Ω and 38 s, to the respective values of (110-124) F/g, 3 Wh/kg, 156 W/kg, 3.4 Ω and 63 s. This study demonstrates that the graphene addition in the GMs has a significant effect on the electrochemical behavior of the electrodes.

Tunable porous structure of carbon nanosheets derived from puffed rice for high energy density supercapacitors

NASA Astrophysics Data System (ADS)

Hou, Jianhua; Jiang, Kun; Tahir, Muhammad; Wu, Xiaoge; Idrees, Faryal; Shen, Ming; Cao, Chuanbao

2017-12-01

The development of green and clean synthetic techniques to overcome energy requirements have motivated the researchers for the utilization of sustainable biomass. Driven by this desire we choose rice as starting materials source. After the explosion effect, the precursor is converted into puffed rice with a honeycomb-like structures composed of thin sheets. These honeycomb-like macrostructures, effectively prevent the cross-linking tendency towards the adjacent nanosheets during activation process. Furthermore, tuneable micro/mesoporous structures with ultrahigh specific surface areas (SBET) are successfully designed by KOH activation. The highest SBET of 3326 m2 g-1 with optimized proportion of small-mesopores is achieved at 850 °C. The rice-derived porous N-doped carbon nanosheets (NCS-850) are used as the active electrode materials for supercapacitors. It exhibites high specific capacitance specifically of 218 F g-1 at 80 A g-1 in 6 M KOH and a high-energy density of 104 Wh kg-1 (53 Wh L-1) in the ionic liquid electrolytes. These are the highest values among the reported biomass-derived carbon materials for the best of our knowledge. The present work demonstrates that the combination of "puffing effect" and common chemical activation can turn natural products such as rice into functional products with prospective applications in high-performance energy storage devices.

[Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

PubMed

Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

2014-01-01

Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.

PubMed

Beales, Ian L P; Garcia-Morales, Carla; Ogunwobi, Olorunseun O; Mutungi, Gabriel

2014-01-25

Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The third wheel: the impact of Twitter use on relationship infidelity and divorce.

PubMed

Clayton, Russell B

2014-07-01

The purpose of this study was to examine how social networking site (SNS) use, specifically Twitter use, influences negative interpersonal relationship outcomes. This study specifically examined the mediational effect of Twitter-related conflict on the relationship between active Twitter use and negative relationship outcomes, and how this mechanism may be contingent on the length of the romantic relationship. A total of 581 Twitter users aged 18 to 67 years (Mage=29, SDage=8.9) completed an online survey questionnaire. Moderation-mediation regression analyses using bootstrapping methods indicated that Twitter-related conflict mediated the relationship between active Twitter use and negative relationship outcomes. The length of the romantic relationship, however, did not moderate the indirect effect on the relationship between active Twitter use and negative relationship outcomes. The results from this study suggest that active Twitter use leads to greater amounts of Twitter-related conflict among romantic partners, which in turn leads to infidelity, breakup, and divorce. This indirect effect is not contingent on the length of the romantic relationship. The current study adds to the growing body of literature investigating SNS use and romantic relationship outcomes.

PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.

PubMed

Lehrke, Michael; Kahles, Florian; Makowska, Anna; Tilstam, Pathricia V; Diebold, Sebastian; Marx, Judith; Stöhr, Robert; Hess, Katharina; Endorf, Elizabeth B; Bruemmer, Dennis; Marx, Nikolaus; Findeisen, Hannes M

2015-04-01

Phosphodiesterase 4 (PDE4) activity mediates cAMP-dependent smooth muscle cell (SMC) activation following vascular injury. In this study we have investigated the effects of specific PDE4 inhibition with roflumilast on SMC proliferation and inflammatory activation in vitro and neointima formation following guide wire-induced injury of the femoral artery in mice in vivo. In vitro, roflumilast did not affect SMC proliferation, but diminished TNF-α induced expression of the vascular cell adhesion molecule 1 (VCAM-1). Specific activation of the cAMP effector Epac, but not PKA activation mimicked the effects of roflumilast on VCAM-1 expression. Consistently, the reduction of VCAM-1 expression was rescued following inhibition of Epac. TNF-α induced NFκB p65 translocation and VCAM-1 promoter activity were not altered by roflumilast in SMCs. However, roflumilast treatment and Epac activation repressed the induction of the activating epigenetic histone mark H3K4me2 at the VCAM-1 promoter, while PKA activation showed no effect. Furthermore, HDAC inhibition blocked the inhibitory effect of roflumilast on VCAM-1 expression. Both, roflumilast and Epac activation reduced monocyte adhesion to SMCs in vitro. Finally, roflumilast treatment attenuated femoral artery intima-media ratio by more than 50% after 4weeks. In summary, PDE4 inhibition regulates VCAM-1 through a novel Epac-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury. PDE4 inhibition and Epac activation might represent novel approaches for the treatment of vascular diseases, including atherosclerosis and in-stent restenosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Amino Acid Specificity for Activation of Phenylalanine Hydroxylase Matches the Specificity for Stabilization of Regulatory Domain Dimers

PubMed Central

2016-01-01

Liver phenylalanine hydroxylase is allosterically activated by phenylalanine. The structural changes that accompany activation have not been identified, but recent studies of the effects of phenylalanine on the isolated regulatory domain of the enzyme support a model in which phenylalanine binding promotes regulatory domain dimerization. Such a model predicts that compounds that stabilize the regulatory domain dimer will also activate the enzyme. Nuclear magnetic resonance spectroscopy and analytical ultracentrifugation were used to determine the ability of different amino acids and phenylalanine analogues to stabilize the regulatory domain dimer. The abilities of these compounds to activate the enzyme were analyzed by measuring their effects on the fluorescence change that accompanies activation and on the activity directly. At concentrations of 10–50 mM, d-phenylalanine, l-methionine, l-norleucine, and (S)-2-amino-3-phenyl-1-propanol were able to activate the enzyme to the same extent as 1 mM l-phenylalanine. Lower levels of activation were seen with l-4-aminophenylalanine, l-leucine, l-isoleucine, and 3-phenylpropionate. The ability of these compounds to stabilize the regulatory domain dimer agreed with their ability to activate the enzyme. These results support a model in which allosteric activation of phenylalanine hydroxylase is linked to dimerization of regulatory domains. PMID:26252467

Role of Proteases in Extra-Oral Digestion of a Predatory Bug, Andrallus spinidens

PubMed Central

Zibaee, Arash; Hoda, Hassan; Mahmoud, Fazeli-Dinan

2012-01-01

Roles of salivary proteases in the extra-oral digestion of the predatory bug, Andrallus spinidens Fabricius (Hemiptera: Pentatomidae) were studied by using 2% azocasein as a general substrate and specific protease substrates, as well as synthetic and endogenous inhibitors. It was found that salivary glands of A. spinidens have two anterior, two lateral, and two posterior lobes. Azocasein was used to measure the activity of general proteases in the salivary glands using different buffer solutions. The enzyme had the highest activity at pH 8. General protease activity was highest at 40 °C and was stable for 6–16 hours. The use of specific substrates showed that trypsin-like, chymotrypsin-like, aminopeptidase, and carboxypeptidase are the active proteases present in salivary glands, by the maximum activity of trypsin-like protease in addition to their optimal pH between 8–9. Ca2+ and Mg2+ increased proteolytic activity about 216%, while other ions decreased it. Specific inhibitors including SBTI, PMSF, TLCK, and TPCK significantly decreased enzyme activity, as well as the specific inhibitors of methalloproteases including phenanthroline, EGTA, and TTHA. Extracted endogenous trypsin inhibitors extracted from potential prey, Chilo suppressalis, Naranga aenescens, Pieris brassicae, Hyphantria cunea, and Ephestia kuhniella, had different effects on trypsin-like protease activity of A. spinidens salivary glands. With the exception of C. suppressalis, the endogenous inhibitors significantly decreased enzyme activity in A. spinidens. PMID:22954419

Characterization and effect of light on the plasma membrane H(+) -ATPase of bean leaves

NASA Technical Reports Server (NTRS)

Linnemeyer, P. A.; Van Volkenburgh, E.; Cleland, R. E.

1990-01-01

Proton excretion from bean (Phaseolus vulgaris L.) leaf cells is increased by bright white light. To test whether this could be due, at least in part, to an increase in plasma membrane (PM) ATPase activity, PM vesicles were isolated from primary leaves by phase partitioning and used to characterize PM ATPase activity and changes in response to light. ATPase activity was characterized as magnesium ion dependent, vanadate sensitive, and slightly stimulated by potassium chloride. The pH optimum was 6.5, the Km was approximately 0.30 millimolar ATP, and the activity was about 60% latent. PM vesicles were prepared from leaves of plants grown for 11 days in dim red light (growing slowly) or grown for 10 days in dim red light and then transferred to bright white-light for 1 day (growing rapidly). For both light treatments, ATPase specific activity was approximately 600 to 700 nanomoles per milligram protein per minute, and the latency, Km, and sensitivity to potassium chloride were also similar. PM vesicles from plants grown in complete darkness, however, exhibited a twofold greater specific activity. We conclude that the promotion of leaf growth and proton excretion by bright white light is not due to an increase in ATPase specific activity. Light does influence ATPase activity, however; both dim red light and bright white light decreased the ATPase specific activity by nearly 50% as compared with dark-grown leaves.

Creating a Professional Blog: The Impact of Student Learning Styles on Perceptions of Learning

ERIC Educational Resources Information Center

Fowler, Kendra; Thomas, Veronica L.

2015-01-01

This article provides marketing educators with a blogging activity that allows students to add to their marketing expertise as well as enhance their communication skills. Specifically, we propose an activity that incorporates the necessary steps for experiential learning to be achieved. Furthermore, the effectiveness of this activity is examined…

Essential Oil Variability and Biological Activities of Tetraclinis articulata (Vahl) Mast. Wood According to the Extraction Time.

PubMed

Djouahri, Abderrahmane; Saka, Boualem; Boudarene, Lynda; Baaliouamer, Aoumeur

2016-12-01

In the present work, the hydrodistillation (HD) and microwave-assisted hydrodistillation (MAHD) kinetics of essential oil (EO) extracted from Tetraclinis articulata (Vahl) Mast. wood was conducted, in order to assess the impact of extraction time and technique on chemical composition and biological activities. Gas chromatography (GC) and GC/mass spectrometry analyses showed significant differences between the extracted EOs, where each family class or component presents a specific kinetic according to extraction time, technique and especially for the major components: camphene, linalool, cedrol, carvacrol and α-acorenol. Furthermore, our findings showed a high variability for both antioxidant and anti-inflammatory activities, where each activity has a specific effect according to extraction time and technique. The highlighted variability reflects the high impact of extraction time and technique on chemical composition and biological activities, which led to conclude that we should select EOs to be investigated carefully depending on extraction time and technique, in order to isolate the bioactive components or to have the best quality of EO in terms of biological activities and preventive effects in food. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

PubMed Central

Hjelm, Brooke E; Kilbourne, Jacquelyn; Herbst-Kralovetz, Melissa M

2014-01-01

Virus-like particles (VLPs) are an active area of vaccine research, development and commercialization. Mucosal administration of VLPs provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. Nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. We compared both intranasal and oral administration of VLPs with a panel of toll-like receptor (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because it is an effective model antigen and an active area of research and commercialization. To prioritize these adjuvants, VLP-specific antibody production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice. Additional distal mucosal sites (nasal, brochoalveolar, salivary, and gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co-delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad-spectrum immune responses, systemically and at distal mucosal sites inducing VLP-specific antibodies at all sites evaluated. In addition, these VLP-specific antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1), supporting their functionality. Oral administration and/or other TLR agonists tested in the panel did not consistently enhance VLP-specific immune responses. This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9 agonists provides dose-sparing advantages for induction of specific and functional antibody responses against VLPs (i.e., non-replicating antigens) in the respiratory, gastrointestinal, and reproductive tract. PMID:24280723

AVX-470: A Novel Oral Anti-TNF Antibody with Therapeutic Potential in Inflammatory Bowel Disease

PubMed Central

Bhol, Kailash C.; Tracey, Daniel E.; Lemos, Brenda R.; Lyng, Gregory D.; Erlich, Emma C.; Keane, David M.; Quesenberry, Michael S.; Holdorf, Amy D.; Schlehuber, Lisa D.; Clark, Shawn A.; Fox, Barbara S.

2013-01-01

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the GI tract that is currently treated with injected monoclonal antibodies specific for tumor necrosis factor (TNF). We developed and characterized AVX-470, a novel polyclonal antibody specific for human TNF. We evaluated the oral activity of AVX-470m, a surrogate antibody specific murine TNF, in several well-accepted mouse models of IBD. Methods AVX-470 and AVX-470m were isolated from the colostrum of dairy cows that had been immunized with TNF. The potency, specificity and affinity of both AVX-470 and AVX-470m were evaluated in vitro and compared with infliximab. AVX-470m was orally administered to mice either before or after induction of colitis and activity was measured by endoscopy, histopathology, immunohistochemistry and quantitative measurement of mRNA levels. Colitis was induced using either 2,4,6-trinitrobenzene sulfonate (TNBS) or dextran sodium sulfate (DSS). Results AVX-470 and AVX-470m were shown to be functionally comparable in vitro. Moreover, the specificity, neutralizing potency and affinity of AVX-470 were comparable to infliximab. Orally administered AVX-470m effectively reduced disease severity in several mouse models of IBD. Activity was comparable to that of oral prednisolone or parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited TNF-driven mucosal inflammation with minimal systemic exposure. Conclusions AVX-470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile comparable to that of infliximab. Oral administration of a surrogate antibody specific for mouse TNF is effective in treating mouse models of IBD, delivering the anti-TNF to the site of inflammation with minimal systemic exposure. PMID:23949620

ISSUES IN ENDOCRINE DISRUPTION: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY

EPA Science Inventory

Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

Recruitment Strategies and Activities Used by Agriculture Teachers.

ERIC Educational Resources Information Center

Myers, Brian E.; Dyer, James E.; Breja, Lisa M.

2003-01-01

The most frequent student recruitment strategies reported by 275 secondary agriculture teachers were (in order of effectiveness) feeder schools, personal contacts, FFA, publications, strong curriculum, support groups, and special events. Specific activities for each strategy were identified. (Contains 34 references.) (SK)

Demonstration of Enantiomer Specificity of Proteins and Drugs

ERIC Educational Resources Information Center

Anderson, Gretchen L.; Page, Shallee T.

2004-01-01

Classroom demonstrations and activities are used to illustrate the properties of enantiomer. During this activity, in a relatively short time students develop a working knowledge of the importance of stereochemistry in biochemistry and its effect on drug design and metabolism.

ASSESSMENT OF THE REPRODUCTIVE AXIS: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY.

EPA Science Inventory

Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

Overexpression of ERβ is sufficient to inhibit hypoxia-inducible factor-1 transactivation

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

Park, Choa; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

2014-07-18

Highlights: • We examined the effect of ERβ specific ligand on HIF-1 inhibition. • DPN down-regulates the ARNT protein levels in PC3 cells. • DPN did not show additional effect in ERβ transfected MCF-7 cells. • Our study shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression. - Abstract: Estrogen receptor (ER) β is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ERβ suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, wemore » attempted to examine the effect of ERβ specific ligand on HIF-1 inhibition in ERβ positive PC3 cells and ERβ transfected MCF-7 cells. ERβ specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ERβ specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ERβ transfected MCF-7 cells. HIF-1 transcriptional activity repression by ERβ was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ERβ significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ERβ. This result shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression.« less

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

PubMed

LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

2006-03-15

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Distinct modes of gene regulation by a cell-specific transcriptional activator.

PubMed

Sengupta, Tanushri; Cohet, Nathalie; Morlé, François; Bieker, James J

2009-03-17

The architectural layout of a eukaryotic RNA polymerase II core promoter plays a role in general transcriptional activation. However, its role in tissue-specific expression is not known. For example, differing modes of its recognition by general transcription machinery can provide an additional layer of control within which a single tissue-restricted transcription factor may operate. Erythroid Kruppel-like factor (EKLF) is a hematopoietic-specific transcription factor that is critical for the activation of subset of erythroid genes. We find that EKLF interacts with TATA binding protein-associated factor 9 (TAF9), which leads to important consequences for expression of adult beta-globin. First, TAF9 functionally supports EKLF activity by enhancing its ability to activate the beta-globin gene. Second, TAF9 interacts with a conserved beta-globin downstream promoter element, and ablation of this interaction by beta-thalassemia-causing mutations decreases its promoter activity and disables superactivation. Third, depletion of EKLF prevents recruitment of TAF9 to the beta-globin promoter, whereas depletion of TAF9 drastically impairs beta-promoter activity. However, a TAF9-independent mode of EKLF transcriptional activation is exhibited by the alpha-hemoglobin-stabilizing protein (AHSP) gene, which does not contain a discernable downstream promoter element. In this case, TAF9 does not enhance EKLF activity and depletion of TAF9 has no effect on AHSP promoter activation. These studies demonstrate that EKLF directs different modes of tissue-specific transcriptional activation depending on the architecture of its target core promoter.

Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

PubMed Central

Lowry, C.A.; Hollis, J.H.; de Vries, A.; Pan, B.; Brunet, L.R.; Hunt, J.R.F.; Paton, J.F.R.; van Kampen, E.; Knight, D.M.; Evans, A.K.; Rook, G.A.W.; Lightman, S.L.

2007-01-01

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes. PMID:17367941

Haemolytic activities and adjuvant effect of Anemone raddeana saponins (ARS) on the immune responses to ovalbumin in mice.

PubMed

Sun, Yongxu; Li, Mingquan; Liu, Jicheng

2008-08-01

In this study, saponins (ARS) extracted from the rhizoma of Anemone raddeana were evaluated for their haemolytic activities and its potential ability as adjuvant on the cellular and humoral immune responses of ICR mice against ovalbumin. The haemolytic activity of ARS was determined using 0.5% rabbit red blood cell. ARS showed a slight haemolytic effect, with its haemolytic percents being 16.50 and 3.56% at the concentrations of 500 and 250 microg/ml, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 mug dissolved in saline containing Alum (200 microg), QuilA (10 and 20 microg) or ARS (50, 100 or 200 microg) on Days 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. ARS significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice especially at a dose of 100 microg (P<0.01 or P<0.05). The OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by ARS compared with OVA control group (P<0.01 or P<0.05). Moreover, no significant differences (P>0.05) were observed between enhancing effect of ARS and QuilA on the OVA-specific IgG2b antibody responses to OVA in mice. The results suggest that ARS showed a slight haemolytic effect and enhanced significantly a specific antibody and cellular response against OVA in mice.

Barriers to physical activity among working mothers.

PubMed

Dombrowski, Jill J

2011-04-01

Working mothers experience several barriers to physical activity. If these barriers can be identified by occupational health nurses and they can partner with working mothers to reduce these perceived barriers, the health of these workers can be improved and chronic disease risk prevented. The purpose of this study was to measure the effect of self-regulatory efficacy on physical activity among working mothers and to describe specific barriers to physical activity. The Barriers Specific Self-Efficacy Scale (BARSE) and the Kaiser Physical Activity Survey (KPAS) were used to measure the variables. Self-regulatory efficacy was found to be a strong predictor of physical activity in a diverse sample of working mothers who did not meet current recommendations for physical activity. Occupational health nurses can use these findings to design programs for groups and for counseling individuals. Copyright 2011, SLACK Incorporated.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells

PubMed Central

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

Background: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. Objective: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Materials and Methods: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. Results: TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Conclusion: Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. SUMMARY Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate-buffered saline; SD: standard deviation; ARE: androgenresponsive element; KLK: kallikrein PMID:28216900

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

PubMed

Le, Van So; Do, Zoe Phuc-Hien; Le, Minh Khoi; Le, Vicki; Le, Natalie Nha-Truc

2014-06-10

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

Roles of s3 site residues of nattokinase on its activity and substrate specificity.

PubMed

Wu, Shuming; Feng, Chi; Zhong, Jin; Huan, Liandong

2007-09-01

Nattokinase (Subtilisin NAT, NK) is a bacterial serine protease with high fibrinolytic activity. To probe their roles on protease activity and substrate specificity, three residues of S3 site (Gly(100), Ser(101) and Leu(126)) were mutated by site-directed mutagenesis. Kinetics parameters of 20 mutants were measured using tetrapeptides as substrates, and their fibrinolytic activities were determined by fibrin plate method. Results of mutation analysis showed that Gly(100) and Ser(101) had reverse steric and electrostatic effects. Residues with bulky or positively charged side chains at position 100 decreased the substrate binding and catalytic activity drastically, while residues with the same characters at position 101 could obviously enhance protease and fibrinolytic activity of NK. Mutation of Leu(126) might impair the structure of the active cleft and drastically decreased the activity of NK. Kinetics studies of the mutants showed that S3 residues were crucial to keep protease activity while they moderately affected substrate specificity of NK. The present study provided some original insight into the P3-S3 interaction in NK and other subtilisins, as well as showed successful protein engineering cases to improve NK as a potential therapeutic agent.

Comparison of four specific dynamic office chairs with a conventional office chair: impact upon muscle activation, physical activity and posture.

PubMed

Ellegast, Rolf P; Kraft, Kathrin; Groenesteijn, Liesbeth; Krause, Frank; Berger, Helmut; Vink, Peter

2012-03-01

Prolonged and static sitting postures provoke physical inactivity at VDU workplaces and are therefore discussed as risk factors for the musculoskeletal system. Manufacturers have designed specific dynamic office chairs featuring structural elements which promote dynamic sitting and therefore physical activity. The aim of the present study was to evaluate the effects of four specific dynamic chairs on erector spinae and trapezius EMG, postures/joint angles and physical activity intensity (PAI) compared to those of a conventional standard office chair. All chairs were fitted with sensors for measurement of the chair parameters (backrest inclination, forward and sideward seat pan inclination), and tested in the laboratory by 10 subjects performing 7 standardized office tasks and by another 12 subjects in the field during their normal office work. Muscle activation revealed no significant differences between the specific dynamic chairs and the reference chair. Analysis of postures/joint angles and PAI revealed only a few differences between the chairs, whereas the tasks performed strongly affected the measured muscle activation, postures and kinematics. The characteristic dynamic elements of each specific chair yielded significant differences in the measured chair parameters, but these characteristics did not appear to affect the sitting dynamics of the subjects performing their office tasks. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Critical Amino Acids in the Active Site of Meprin Metalloproteinases for Substrate and Peptide Bond Specificity*

PubMed Central

Villa, James P.; Bertenshaw, Greg P.; Bond, Judith S.

2008-01-01

SUMMARY The protease domains of the evolutionarily-related α and ß subunits of meprin metalloproteases are approximately 55% identical at the amino acid level, however, their substrate and peptide bond specificities differ markedly. The meprin ß subunit favors acidic residues proximal to the scissile bond, while the α subunit prefers small or aromatic amino acids flanking the scissile bond. Thus gastrin, a peptide that contains a string of five Glu residues, is an excellent substrate for meprin ß while it is not hydrolyzed by meprin α. Work herein aimed to identify critical amino acids in the meprin active sites that determine the substrate specificity differences. Sequence alignments and homology models, based on the crystal structure of the crayfish astacin, showed electrostatic differences within the meprin active sites. Site-directed mutagenesis of active site residues demonstrated that replacement of a hydrophobic residue by a basic amino acid enabled the meprin α protease to cleave gastrin. The meprin αY199K mutant was most effective; the corresponding mutation of meprin ßK185Y resulted in decreased activity toward gastrin. Peptide cleavage site determinations and kinetic analyses using a variety of peptides extended evidence that meprin αTyr199/ßLys185 are substrate specificity determinants in meprin active sites. These studies shed light on the molecular basis for the substrate specificity differences of astacin metalloproteinases. PMID:12888571

Effects of an inhibitor of tripeptidyl peptidase II (Ala-Ala-Phe-chloromethylketone) and its combination with an inhibitor of the chymotrypsin-like activity of the proteasome (PSI) on apoptosis, cell cycle and proteasome activity in U937 cells.

PubMed

Bury, M; Młynarczuk, I; Pleban, E; Hoser, G; Kawiak, J; Wójcik, C

2001-01-01

AAF-AMC is not a specific TPP II substrate, since it is also hydrolyzed by purified proteasomes. Moreover, AAF-cmk, claimed to be a specific TPP II inhibitor, also inhibits the chymotrypsin-like activity of the proteasome. While AAF-cmk itself is mildly cytostatic to U-937 cells and induces cell cycle block in G1, its combination with PSI does not induce an increase in the cytostatic/cytotoxic effects. This suggests that TPP II is possibly less important for cell metabolism than it was previously believed and it is less probable that it can be able to fully compensate for the loss of the proteasome function.

[The future of methotrexate therapy and other folate inhibitors].

PubMed

Fiehn, C

2011-02-01

Because of its good effectiveness and tolerability, methotrexate (MTX) has been the most important DMARD for the treatment of rheumatoid arthritis (RA) worldwide for many years. Thus the treatment of this disease is strongly based on the principle of folate inhibition. Recent years have brought new insights into the pharmacology and mechanisms of action of MTX. As a result, it now appears possible to further develop folate inhibitors to increase effectiveness and specificity. Polyglutamation of the drug, a metabolic step which appears to play a role both in terms of therapeutic effects and hepatic side effects, might be a possible starting point. Moreover, methods of targeted drug delivery intended to increase drug accumulation at the site of inflammation can increase the effectiveness of treatment and reduce toxicity. Albumin-coupled and liposomally-conjugated MTX, both of which inhibit inflammation in animal models more potently than MTX, are undergoing preclinical evaluation. It was recognized that activated synovial macrophages upregulate folate receptor ß (FR-ß) expression and that MTX can become active by this pathway. This finding makes it possible to develop new FR-ß-specific folate inhibitors with specificity for this pathophysiologically important cell population.

Stringency of substrate specificity of Escherichia coli malate dehydrogenase.

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

Boernke, W. E.; Millard, C. S.; Stevens, P. W.

1995-09-10

Malate dehydrogenase and lactate dehydrogenase are members of the structurally and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes display high specificity for their respective keto substrates, oxaloacetate and pyruvate. Closer analysis of their specificity, however, reveals that the specificity of malate dehydrogenase is much stricter and less malleable than that of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an attempt to reverse their specificity has met with contrary results. Conversion of a specific active-site glutamine to arginine in lactate dehydrogenase from Bacillus stearothermophilus generated an enzyme that displayed activity toward oxaloacetate equal to that of the nativemore » enzyme toward pyruvate (H. M. Wilks et al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in the mobile, active site loop of the Escherichia coli malate dehydrogenase that incorporate the complementary change, conversion of arginine 81 to glutamine, to evaluate the role of charge distribution and conformational flexibility within this loop in defining the substrate specificity of these enzymes. Mutants incorporating the change R81Q all had reversed specificity, displaying much higher activity toward pyruvate than to the natural substrate, oxaloacetate. In contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants were much less active than the native enzyme. Secondary mutations within the loop of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only moderately beneficial effects on the activity of the mutant enzyme toward pyruvate. The mutation A80P, which can be expected to reduce the overall flexibility of the loop, modestly improved activity toward pyruvate. The possible physiological relevance of the stringent specificity of malate dehydrogenase was investigated. In normal strains of E. coli, fermentative metabolism was not affected by expression of the mutant malate dehydrogenase. However, when expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme restored growth and produced lactic acid as the sole fermentation product.« less

Mineralization of LCFA associated with anaerobic sludge: Kinetics, enhancement of methanogenic activity, and effect of VFA.

PubMed

Pereira, M A; Sousa, D Z; Mota, M; Alves, M M

2004-11-20

Long-chain fatty acids (LCFA) associated with anaerobic sludge by mechanisms of precipitation, adsorption, or entrapment can be biodegraded to methane. The mineralization kinetics of biomass-associated LCFA were established according to an inhibition model based on Haldane's enzymatic inhibition kinetics. A value around 1,000 mg COD-LCFA..g VSS(-1) was obtained for the optimal specific LCFA content that allowed the maximal mineralization rate. For sludge with specific LCFA contents of 2,838 +/- 63 and 4,571 +/- 257 mg COD-LCFA..g VSS(-1), the specific methanogenic activities in the presence of acetate, butyrate, and H(2)/CO(2) were significantly enhanced after the mineralization of the biomass-associated LCFA. For sludge with a specific LCFA content near the optimal value defined by the kinetic model, the effect of adding VFA to the medium was studied during the mineralization of the biomass-associated LCFA. Different patterns were obtained for each individual substrate. Acetate and butyrate were preferentially consumed by the consortium, but in the case of propionate no evidence of a sequential consumption pattern could be withdrawn. It was concluded that LCFA do not exert a bactericidal neither a permanent toxic effect toward the anaerobic consortia. A discussion is addressed to the relative roles of a reversible inhibitory effect and a transport limitation effect imposed by the LCFA surrounding the cells. (c) 2004 Wiley Periodicals, Inc

Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity.

PubMed

Wells, James W; Cowled, Chris J; Darling, David; Guinn, Barbara-Ann; Farzaneh, Farzin; Noble, Alistair; Galea-Lauri, Joanna

2007-12-01

Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.

Feedback Specificity, Information Processing, and Transfer of Training

ERIC Educational Resources Information Center

Goodman, Jodi S.; Wood, Robert E.; Chen, Zheng

2011-01-01

This study examines the effects of feedback specificity on transfer of training and the mechanisms through which feedback can enhance or inhibit transfer. We used concurrent verbal protocol methodology to elicit and operationalize the explicit information processing activities used by 48 trainees performing the Furniture Factory computer…

What are the most effective intervention techniques for changing physical activity self-efficacy and physical activity behaviour--and are they the same?

PubMed

Williams, S L; French, D P

2011-04-01

There is convincing evidence that targeting self-efficacy is an effective means of increasing physical activity. However, evidence concerning which are the most effective techniques for changing self-efficacy and thereby physical activity is lacking. The present review aims to estimate the association between specific intervention techniques used in physical activity interventions and change obtained in both self-efficacy and physical activity behaviour. A systematic search yielded 27 physical activity intervention studies for 'healthy' adults that reported self-efficacy and physical activity data. A small, yet significant (P < 0.01) effect of the interventions was found on change in self-efficacy and physical activity (d = 0.16 and 0.21, respectively). When a technique was associated with a change in effect sizes for self-efficacy, it also tended to be associated with a change (r(s) = 0.690, P < 0.001) in effect size for physical activity. Moderator analyses found that 'action planning', 'provide instruction' and 'reinforcing effort towards behaviour' were associated with significantly higher levels of both self-efficacy and physical activity. 'Relapse prevention' and 'setting graded tasks' were associated with significantly lower self-efficacy and physical activity levels. This meta-analysis provides evidence for which psychological techniques are most effective for changing self-efficacy and physical activity.

Using TENS for pain control: the state of the evidence

PubMed Central

Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

2014-01-01

Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

The role of the left anterior temporal lobe in semantic composition vs. semantic memory.

PubMed

Westerlund, Masha; Pylkkänen, Liina

2014-05-01

The left anterior temporal lobe (LATL) is robustly implicated in semantic processing by a growing body of literature. However, these results have emerged from two distinct bodies of work, addressing two different processing levels. On the one hand, the LATL has been characterized as a 'semantic hub׳ that binds features of concepts across a distributed network, based on results from semantic dementia and hemodynamic findings on the categorization of specific compared to basic exemplars. On the other, the LATL has been implicated in combinatorial operations in language, as shown by increased activity in this region associated with the processing of sentences and of basic phrases. The present work aimed to reconcile these two literatures by independently manipulating combination and concept specificity within a minimal MEG paradigm. Participants viewed simple nouns that denoted either low specificity (fish) or high specificity categories (trout) presented in either combinatorial (spotted fish/trout) or non-combinatorial contexts (xhsl fish/trout). By combining these paradigms from the two literatures, we directly compared the engagement of the LATL in semantic memory vs. semantic composition. Our results indicate that although noun specificity subtly modulates the LATL activity elicited by single nouns, it most robustly affects the size of the composition effect when these nouns are adjectivally modified, with low specificity nouns eliciting a much larger effect. We conclude that these findings are compatible with an account in which the specificity and composition effects arise from a shared mechanism of meaning specification. Copyright © 2014 Elsevier Ltd. All rights reserved.

DISPERSION OF RADIOACTIVE ISOTOPES IN THE SOIL BY EARTHWORMS (in Russian)

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

Peredel'skii, A.A.; Shain, S.S.; Karavyanskii, N.S.

1960-11-01

The effects of earthworms on the distribution and migration of radioisotopes in contaminated earth were investigated. Data on the mean Ca/sup 45/ and Sr/sup 90/ activity of a single worm and its coprolith in contaminated soil are tabulated. It is shown that the specific radioactivity in the earthworm quickly reaches a maximum and remains unchanged during further inhabitance in the contuminated soil. The specific activity of the earthworm can reach that of the soil; however, after leaving the contuminated area, the activity is rapidly reduced in the worm. The specific activity of the earthworm coprolith is close to that ofmore » the body; sometimes it exceeds the activity of both the body and the soil due to uptake of organic material of higher radioactivity. The experiment shows that the influence of earthworms on dissemination of shont-lifs isotopes is negligible but that with long-life isotopes it may be more noticeable. (R.V.J.)« less

Classroom Activities: Simple Strategies to Incorporate Student-Centered Activities within Undergraduate Science Lectures

PubMed Central

Lom, Barbara

2012-01-01

The traditional science lecture, where an instructor delivers a carefully crafted monolog to a large audience of students who passively receive the information, has been a popular mode of instruction for centuries. Recent evidence on the science of teaching and learning indicates that learner-centered, active teaching strategies can be more effective learning tools than traditional lectures. Yet most colleges and universities retain lectures as their central instructional method. This article highlights several simple collaborative teaching techniques that can be readily deployed within traditional lecture frameworks to promote active learning. Specifically, this article briefly introduces the techniques of: reader’s theatre, think-pair-share, roundtable, jigsaw, in-class quizzes, and minute papers. Each technique is broadly applicable well beyond neuroscience courses and easily modifiable to serve an instructor’s specific pedagogical goals. The benefits of each technique are described along with specific examples of how each technique might be deployed within a traditional lecture to create more active learning experiences. PMID:23494568

Feature Statistics Modulate the Activation of Meaning During Spoken Word Processing.

PubMed

Devereux, Barry J; Taylor, Kirsten I; Randall, Billi; Geertzen, Jeroen; Tyler, Lorraine K

2016-03-01

Understanding spoken words involves a rapid mapping from speech to conceptual representations. One distributed feature-based conceptual account assumes that the statistical characteristics of concepts' features--the number of concepts they occur in (distinctiveness/sharedness) and likelihood of co-occurrence (correlational strength)--determine conceptual activation. To test these claims, we investigated the role of distinctiveness/sharedness and correlational strength in speech-to-meaning mapping, using a lexical decision task and computational simulations. Responses were faster for concepts with higher sharedness, suggesting that shared features are facilitatory in tasks like lexical decision that require access to them. Correlational strength facilitated responses for slower participants, suggesting a time-sensitive co-occurrence-driven settling mechanism. The computational simulation showed similar effects, with early effects of shared features and later effects of correlational strength. These results support a general-to-specific account of conceptual processing, whereby early activation of shared features is followed by the gradual emergence of a specific target representation. Copyright © 2015 The Authors. Cognitive Science published by Cognitive Science Society, Inc.

78 FR 39296 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... Information Collection Activity; Comment Request Proposed Projects Title: State Abstinence Education Program... accurate and effective abstinence-based plans responsive to their specific needs and inclusive of vulnerable populations. These plans must provide abstinence education, and at the option of the State, where...

Exercise Do's and Don'ts: Guidelines for Fitness Activities.

ERIC Educational Resources Information Center

Burgess, Sharon

Many common exercises are contraindicated due to their potential for injury relative to benefit produced. Specific contraindicated exercises are discussed, and safer, more effective exercises are recommended. Current stretching and toning guidelines are also given which apply to all fitness activities. (Author)

The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Moderates an Effect of Physical Activity on Working Memory Performance

PubMed Central

Erickson, Kirk I.; Banducci, Sarah E.; Weinstein, Andrea M.; MacDonald, Angus W.; Ferrell, Robert E.; Halder, Indrani; Flory, Janine D.; Manuck, Stephen B.

2014-01-01

Physical activity enhances cognitive performance, yet individual variability in its effectiveness limits its widespread therapeutic application. Genetic differences might be one source of this variation. For example, carriers of the methionine-specifying (Met) allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have reduced secretion of BDNF and poorer memory, yet physical activity increases BDNF levels. To determine whether the BDNF polymorphism moderated an association of physical activity with cognitive functioning among 1,032 midlife volunteers (mean age = 44.59 years), we evaluated participants’ performance on a battery of tests assessing memory, learning, and executive processes, and evaluated their physical activity with the Paffenbarger Physical Activity Questionnaire. BDNF genotype interacted robustly with physical activity to affect working memory, but not other areas of cognitive functioning. In particular, greater levels of physical activity offset a deleterious effect of the Met allele on working memory performance. These findings suggest that physical activity can modulate domain-specific genetic (BDNF) effects on cognition. PMID:23907543

Effect of pineal tetrapeptide on antioxidant defense in Drosophila melanogaster.

PubMed

Khavinson, V K; Myl'nikov, S V

2000-04-01

Effects of synthetic pineal tetrapeptide L-Ala-L-Glu-L-Asp-L-Glu (Epithalon) on specific catalase activity and the content of conjugated hydroperoxides in highly inbred Drosophila melanogaster lines differing in reproductive functions were studied. It was shown that Epithalon is a potent modulator of the antioxidant defense, whose biological activity 1000-fold surpasses that of the complex pineal peptide preparation Epithalamin.

Hemispheric dissociation of reward processing in humans: insights from deep brain stimulation.

PubMed

Palminteri, Stefano; Serra, Giulia; Buot, Anne; Schmidt, Liane; Welter, Marie-Laure; Pessiglione, Mathias

2013-01-01

Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motivation paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor effectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manipulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson's disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tissue-specific regulation of malic enzyme by thyroid hormone in the neonatal rat.

PubMed

Sood, A; Schwartz, H L; Oppenheimer, J H

1996-05-15

Two recent studies have claimed that thyroid hormone administration accelerates malic enzyme gene expression in the neonatal brain in contrast to the well-documented lack of effect of triiodothyronine on malic enzyme gene expression in the adult brain. Since these observations conflict with earlier observations in our laboratory, we reinvestigated the effect of thyroid hormone status on the ontogeny of malic enzyme gene expression in the neonatal rat. Neither hypothyroidism nor hyperthyroidism influenced the ontogenesis of malic enzyme activity in neonatal brain whereas the patterns of gene expression and enzyme activity in liver were markedly affected. Our results suggest that tissue-specific factors in brain block thyroid hormone-induced gene expression by thyroid hormone.

The active site architecture in peroxiredoxins: a case study on Mycobacterium tuberculosis AhpE.

PubMed

Pedre, Brandán; van Bergen, Laura A H; Palló, Anna; Rosado, Leonardo A; Dufe, Veronica Tamu; Molle, Inge Van; Wahni, Khadija; Erdogan, Huriye; Alonso, Mercedes; Proft, Frank De; Messens, Joris

2016-08-11

Peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. A nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. We used the Mycobacterium tuberculosis alkyl hydroperoxide reductase E (MtAhpE) as a model to investigate the effect of the chemical environment on the specificity of the reaction. Using an integrative structural (R116A - PDB ; F37H - PDB ), kinetic and computational approach, we explain the mutational effects of key residues in its environment. This study shows that the active site residues are specifically oriented to create an environment which selectively favours a reaction with peroxides.

Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: A review.

PubMed

Zhu, Fengmei; Du, Bin; Xu, Baojun

2018-05-24

Inflammation is the first biological response of the immune system to infection, injury or irritation. Evidence suggests that the anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ as well as noncytokine mediator, prostaglandin E 2 . Fruits, vegetables, and food legumes contain high levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions have not been completely identified. The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes. Specific cytokines released for specific type of physiological event might shed some light on the specific use of each source of phytochemicals that can benefit to counter the inflammatory response. As natural modulators of proinflammatory gene expressions, phytochemical from fruits, vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulations of various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the natural promotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruits and vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectins and peptides had anti-inflammatory activity in most cases. However, there are lack of human study data on the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes.

Comparative study of two methods of fractionation bromelain from pineapple core extract (Ananas comosus)

NASA Astrophysics Data System (ADS)

Febriani, K.; Wahyuni, I.; Setiasih, S.; Hudiyono, S.

2017-07-01

The enzyme can be purified by fractional precipitation. This can be done by salt or organic solvent. In this research, purification of bromelain from pineapple core by fractional precipitation was done by 2 compounds, ammonium sulfate, and ethanol. Fractional precipitation by ammonium sulfate proved to be more effective as it yielded a higher specific activity. Specific activity by ethanol and ammonium sulfate is 4.6480 U/mg at 0-60 % saturation and 8.2243 U/mg at 50-80 % saturation.

Competition and cooperation among similar representations: toward a unified account of facilitative and inhibitory effects of lexical neighbors.

PubMed

Chen, Qi; Mirman, Daniel

2012-04-01

One of the core principles of how the mind works is the graded, parallel activation of multiple related or similar representations. Parallel activation of multiple representations has been particularly important in the development of theories and models of language processing, where coactivated representations (neighbors) have been shown to exhibit both facilitative and inhibitory effects on word recognition and production. Researchers generally ascribe these effects to interactive activation and competition, but there is no unified explanation for why the effects are facilitative in some cases and inhibitory in others. We present a series of simulations of a simple domain-general interactive activation and competition model that is broadly consistent with more specialized domain-specific models of lexical processing. The results showed that interactive activation and competition can indeed account for the complex pattern of reversals. Critically, the simulations revealed a core computational principle that determines whether neighbor effects are facilitative or inhibitory: strongly active neighbors exert a net inhibitory effect, and weakly active neighbors exert a net facilitative effect.

Implementation intentions for physical activity behavior in older adult women: an examination of executive function as a moderator of treatment effects.

PubMed

Hall, Peter A; Zehr, Christopher; Paulitzki, Jeffrey; Rhodes, Ryan

2014-08-01

Implementation intentions are effective for enhancing physical activity, but it is unknown how well these effects extend to older adults and/or are modified by cognitive variables. Our objective is to examine (1) the efficacy of an implementation intentions intervention for physical activity in older adult women and (2) to examine the moderating effects of executive function. Participants (N = 75, M age = 73.72) completed measures of executive function and were randomly assigned to weekly implementation intentions for physical activity (experimental condition), implementation intentions for an unrelated behavior (control condition), or no treatment. Baseline activity was measured by accelerometer and self-report; follow-up activity was measured by weekly self-report. Findings indicated a significant treatment effect for the experimental condition and a treatment by executive function interaction. Specifically, participants with relatively stronger executive function benefited most from the experimental intervention. Implementation intentions are effective for enhancing physical activity among older adult women, and the effects may be especially pronounced for those with relatively stronger executive function.

Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues.

PubMed

Riese, Cornelia; Michaelis, Marten; Mentrup, Birgit; Götz, Franziska; Köhrle, Josef; Schweizer, Ulrich; Schomburg, Lutz

2006-12-01

Important enzymes for thyroid hormone metabolism, antioxidative defense, and intracellular redox control contain selenocysteine (Sec) in their active centers. Expression of these selenoproteins is tightly controlled, and a sex-specific phenotype is observed on disturbance of selenium (Se) transport in mice. Therefore, we analyzed Se concentrations and expression levels of several selenoproteins including type I iodothyronine deiodinase (Dio1) and glutathione peroxidase (GPx) isozymes in male and female mice. On regular lab chow, serum Se levels were comparable, but serum GPx3 activity was higher in females than males (1.3-fold). Selenoprotein P (SePP) mRNA levels were higher in livers (1.3-fold) and lower in kidneys (to 31%) in female compared with male mice. Orchidectomy alleviated the sex-specific differences in SePP mRNA amounts, indicating modulatory effects of androgens on SePP expression. Female mice expressed higher levels of Dio1 mRNA in kidney (2.6-fold) and liver (1.4-fold) in comparison with male mice. This sexual dimorphic expression of Dio1 mRNA was paralleled by increased Dio1 activity in female kidney (1.8-fold) but not in liver in which males expressed higher Dio1 activity (2.8-fold). Interestingly, Se deficiency decreased Dio1 activity more effectively in males than females, and resulting hepatic enzyme levels were then comparable between the sexes. At the same time, the sex-specific difference of Dio1 activity widened in kidney. Orchidectomy or estradiol treatment of ovariectomized females impacted stronger on renal than hepatic Dio1 expression. Thus, we conclude that Se-dependent posttranscriptional mechanisms are operational that affect either translational efficiency or Dio1 stability in a sex- and tissue-specific manner.

Effects of surface chemical properties of activated carbon modified by amino-fluorination for electric double-layer capacitor.

PubMed

Jung, Min-Jung; Jeong, Euigyung; Cho, Seho; Yeo, Sang Young; Lee, Young-Seak

2012-09-01

The surface of phenol-based activated carbon (AC) was seriatim amino-fluorinated with solution of ammonium hydroxide and hydrofluoric acid in varying ratio to fabricate electrode materials for use in an electric double-layer capacitor (EDLC). The specific capacitance of the amino-fluorinated AC-based EDLC was measured in a 1 M H(2)SO(4) electrolyte, in which it was observed that the specific capacitances increased from 215 to 389 Fg(-1) and 119 and 250 Fg(-1) with the current densities of 0.1 and 1.0 Ag(-1), respectively, in comparison with those of an untreated AC-based EDLC when the amino-fluorination was optimized via seriatim mixed solution of 7.43 mol L(-1) ammonium hydroxide and 2.06 mol L(-1) hydrofluoric acid. This enhancement of capacitance was attributed to the synergistic effects of an increased electrochemical activity due to the formation of surface N- and F-functional groups and increased, specific surface area, and mesopore volumes, all of which resulted from the amino-fluorination of the electrode material. Copyright © 2012 Elsevier Inc. All rights reserved.

(14)C levels in the vicinity of the Fukushima Dai-ichi Nuclear Power Plant prior to the 2011 accident.

PubMed

Xu, Sheng; Cook, Gordon T; Cresswell, Alan J; Dunbar, Elaine; Freeman, Stewart P H T; Hastie, Helen; Hou, Xiaolin; Jacobsson, Piotr; Naysmith, Philip; Sanderson, David C W; Tripney, Brian G; Yamaguchi, Katsuhiko

2016-06-01

A 50-year-old Japanese cedar (Cryptomeria japonica) from Okuma, ∼1 km southwest of the Fukushima Dai-ichi Nuclear Power Plant, was cored and each annual ring was analysed for (14)C. The (14)C specific activity values varied from 330.4 Bq kg(-1) C in the tree ring formed in 1971 to 231.2 Bq kg(-1) C in the 2014 ring. During the periods 1971-1976 and 2011-2014, the (14)C specific activities are indistinguishable from the ambient background values. However, compared with the ambient atmospheric levels, the (14)C specific activities between 1977 and 2010 are significantly elevated, clearly indicating (14)C discharges from the reactors during their normal operations. In addition, the specific activities are positively correlated with the annual electricity generation values. The excess (14)C specific activities were <36 Bq kg(-1) C, corresponding to an additional annual effective dose of <2 μSv via the food ingestion pathway in the study location. The primary wind direction is east-southeast/southeast with a frequency of ∼30%, in comparison to ∼20% frequency for the direction of the site under study (north-northeast/northeast). This would tend to indicate a similar magnitude of additional effective dose and consequently no significant radiological impact of atmospheric (14)C discharges from the FDNPP during the entire period of normal operations. Additionally, no (14)C pulse in activity can be observed in the year 2011 ring. This might be caused by a limited (14)C release from the damaged reactors during the accident or that the prevailing wind during the short period of release (11th-25th March 2011) was not in the direction of Okuma. Copyright © 2016 Elsevier Ltd. All rights reserved.

UNDERSTANDING THE EFFECTS OF ATRAZINE ON STEROIDOGENESIS IN THE HUMAN H295R AND RAT GRANULOSA CELLS

EPA Science Inventory

The effects of environmental chemicals on the catalytic activity of steroidogenic enzymes, including aromatase, have been well documented. However, specific effects of environmental chemicals on steroidogenesis and the physiological impact on local and systemic concentrations of ...

The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling.

PubMed

Ghosh, Mithun; Kim, In Sook; Lee, Young Min; Hong, Seong Min; Lee, Taek Hwan; Lim, Ji Hong; Debnath, Trishna; Lim, Beong Ou

2018-03-08

This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun- N -terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin β₃. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.

Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination.

PubMed

Kim, Aeyung; Noh, Young-Woock; Kim, Kwang Dong; Jang, Yong-Suk; Choe, Yong-Kyung; Lim, Jong-Seok

2004-10-31

Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL), which is responsible for tumor protection and regression. In this study, we examined whether DCs pulsed with necrotic tumor lysates can efficiently prevent malignant melanoma tumor cell metastasis to the lung. DCs derived from mouse bone marrow were found to produce remarkably elevated levels of IL-12 after being pulsed with the tumor lysates. Moreover, immunization with these DCs induced CTL activation and protected mice from metastasis development by intravenously inoculated tumor cells. In addition, these DCs activated NK cells in vitro in a contact-dependent manner, and induced NK activities in vivo. Furthermore, NK cell depletion before DC vaccination significantly reduced the tumor-specific CTL activity, IFN-gamma production, and IFN-gamma- inducible gene expression, and eventually interfered with the antitumor effect of tumor-pulsed DCs. Finally, similar findings with respect to NK cell dependency were obtained in the C57BL/ 6J-bg/bg mice, which have severe deficiency in cytolytic activity of NK cells. These data suggest that the antitumor effect elicited by DC vaccination, at least in a B16 melanoma model, requires the participation of both cytolytic NK and CD8(+) T cells. The findings of this study would provide important data for the effective design of DC vaccines for cancer immunotherapy.

[Mechanism for synergistic effect of IRF4 and MITF on tyrosinase promoter].

PubMed

Song, Jian; Liu, Xueming; Li, Jiada; Liu, Huadie; Peng, Zhen; Chen, Hongsheng; Mei, Lingyun; He, Chufeng; Feng, Yong

2018-05-28

To investigate the mechanism for the synergistic effect of interferon regulatory factor 4 (IRF4) and microphthalmia-associated transcription factor (MITF) on tyrosinase (TYR) promoter.
 Methods: The synergistic transcriptional effect, subcellular localization, and protein-protein interaction for IRF4 and MITF were observed by luciferase assay, immunofluorescence, GST-pull down, and co-immunoprecipitation, respectively.
 Results: IRF4 and MITF proteins were co-expressed in the cell nucleus. IRF4 augmented the transcriptional function of MITF (but not the mutant MITF) to activate the expression of the TYR promoter, but with no effect on other MITF-specific target promoters. IRF4 alone did not affect TYR promoter significantly. No direct interaction between the two proteins was noted.
 Conclusion: IRF4 and MITF exert a specifically synergistic effect on activation of TYR promoter through IRF4-mediated upregulation of transcriptional function of MITF. This synergistic effect is mainly regulated by MITF; DNA might be involved in the interaction between the two proteins.

THE EFFECT OF IONIZING RADIATION ON ACETYLCHOLINE METABOLISM IN MACACA- RHESUS MONKEYS

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

Demin, N.N.; Korneeva, N.V.; Shaternikov, V.A.

1961-11-01

In macaca-rhesus monkeys the normal content of free acetylcholine in the mucosa of the small intestine was higher, as it was in brain and liver, than bound acetyl choline. The total cholinesterase activity and, particularly, the activity of acetylcholinesterase and non-specific cholinesterase in control monkeys is highest in brain, followed by intestinal mucosa and liver. One to three days after gamma -irradiation of the monkey at a dose of 600 r the amount of free and bound acetylcholine in the mucosa of the small intestine increased, while it decreased in liver. The total cholinesterase activity in the mucosa of themore » small intestine during this period increased, in general because of the increase in the activity of non-specific cholinesterase. In the liver the increase in total cholinesterase activity also occurred because of an increase in non-specific cholinesterase activity, but was less clear-cut and occurred later (the third day after irradiation). In animals irradiated 2 to 3 years before the investigation, an increased concentration of free acetylcholine in brain, liver, and mucosa of the small intestine was noted; but there were no ehanges in bound acetylcholine. The total cholinesterase activity increased in liver as a result of acetyl cholinesterase increase and non-specific enzymes, and in mucosa of the small intestine only as a result of acetylcholinesterase activity. In brain the total cholinesterase activity decreased as a consequence of a decrease in acetylcholinesterase activity. (auth)« less

Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination

PubMed Central

Miura, Kazutoyo; Zhou, Hong; Moretz, Samuel E.; Diouf, Ababacar; Thera, Mahamadou A; Dolo, Amagana; Doumbo, Ogobara; Malkin, Elissa; Diemert, David; Miller, Louis H.; Mullen, Gregory E.D.; Long, Carole A.

2009-01-01

Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the U.S. with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active antibodies judged by an in vitro parasite Growth Inhibition Assay (GIA). However, the same vaccine in Malian adults did not increase biological activity although it elevated ELISA titers. As GIA has been used to evaluate the biological activity of antibodies induced by blood-stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific antibodies from both US vaccinees and from non-vaccinated individuals living in a malaria-endemic area of Mali, and performed ELISA and GIA. Both AMA1-specifc antibodies induced by vaccination (US) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG which did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 antibodies from US vaccinees; in contrast, US-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both US- and Mali-AMA1-specific antibodies showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific antibody by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of antibodies induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood-stage malaria vaccine. PMID:19050299

Quantification of growth factor signaling and pathway cross talk by live-cell imaging.

PubMed

Gross, Sean M; Rotwein, Peter

2017-03-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor-receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras-Raf-Mek-ERK and phosphatidylinositol (PI) 3-kinase-Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. Copyright © 2017 the American Physiological Society.

Quantification of growth factor signaling and pathway cross talk by live-cell imaging

PubMed Central

Gross, Sean M.

2017-01-01

Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor–receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras–Raf–Mek–ERK and phosphatidylinositol (PI) 3-kinase–Akt. Incubation of cells with epidermal growth factor (EGF) resulted in rapid, robust, and sustained ERK signaling but shorter-term activation of Akt. In contrast, hepatocyte growth factor induced sustained Akt signaling but weak and short-lived ERK activity, and insulin-like growth factor-I stimulated strong long-term Akt responses but negligible ERK signaling. To address potential interactions between signaling pathways, we employed specific small-molecule inhibitors. In cells incubated with EGF or platelet-derived growth factor-AA, Raf activation and the subsequent stimulation of ERK reduced Akt signaling, whereas Mek inhibition, which blocked ERK activation, enhanced Akt and turned transient effects into sustained responses. Our results reveal that individual growth factors initiate signaling cascades that vary markedly in strength and duration and demonstrate in living cells the dramatic effects of cross talk from Raf and Mek to PI 3-kinase and Akt. Our data further indicate how specific growth factors can encode distinct cellular behaviors by promoting complex interactions among signaling pathways. PMID:28100485

Age-specific strategies for immunization reminders and recalls: a registry-based randomized trial.

PubMed

Dombkowski, Kevin J; Costello, Lauren E; Harrington, Laura B; Dong, Shiming; Kolasa, Maureen; Clark, Sarah J

2014-07-01

Although previous studies have found reminder/recall to be effective in increasing immunization rates, little guidance exists regarding the specific ages at which it is optimal to send reminder/recall notices. To assess the relative effectiveness of centralized reminder/recall strategies targeting age-specific vaccination milestones among children in urban areas during June 2008-June 2009. Three reminder/recall strategies used capabilities of the Michigan Care Improvement Registry (MCIR), a statewide immunization information system: a 7-month recall strategy, a 12-month reminder strategy, and a 19-month recall strategy. Eligible children were randomized to notification (intervention) or no notification groups (control). Primary study outcomes included MCIR-recorded immunization activity (administration of ≥1 new dose, entry of ≥1 historic dose, entry of immunization waiver) within 60 days following each notification cycle. A total of 10,175 children were included: 2,072 for the 7-month recall, 3,502 for the 12-month reminder, and 4,601 for the 19-month recall. Immunization activity was similar between notification versus no notification groups at both 7 and 12 months. Significantly more 19-month-old children in the recall group (26%) had immunization activity compared to their counterparts who did not receive a recall notification (19%). Although recall notifications can positively affect immunization activity, the effect may vary by targeted age group. Many 7- and 12-month-olds had immunization activity following reminder/recall; however, levels of activity were similar irrespective of notification, suggesting that these groups were likely to receive medical care or immunization services without prompting. Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.

Teacher and student perspectives on motivation within the high school science classroom

NASA Astrophysics Data System (ADS)

Pickens, Melanie Turnure

The purpose of this study was to investigate teacher and student perspectives on the motivation of high school science students and to explore specific motivational strategies used by teachers as they attempt to enhance student motivation. Four science teachers took part in an initial audio-taped interview, classroom observations with debriefing conversations, and a final audio-taped interview to discuss findings and allow member checking for data triangulation and interpretation. Participating teachers also took part in a final focus group interview. Student participants from each teacher's class were given a Likert style anonymous survey on their views about motivation and learning, motivation in science class, and specific motivational strategies that emerged in their current science class. This study focused on effective teaching strategies for motivation commonly used by the four teachers and on specific teaching strategies used by two of these four teachers in different tracks of science classes. The intent was to determine not only what strategies worked well for all types of science classes, but also what specific motivational approaches were being used in high and low tracked science classes and the similarities and differences between them. This approach provided insight into the differences in motivating tracked students, with the hope that other educators in specific tracks might use such pedagogies to improve motivation in their own science classrooms. Results from this study showed that science teachers effectively motivate their students in the following ways: Questioning students to engage them in the lesson, exhibiting enthusiasm in lesson presentations, promoting a non-threatening environment, incorporating hands-on activities to help learn the lesson concepts, using a variety of activities, believing that students can achieve, and building caring relationships in the classroom. Specific to the higher tracked classroom, effective motivational strategies included: Use of teacher enthusiasm, promoting a non-threatening class atmosphere, and connecting the adolescent world to science. In the lower tracked classroom, specific effective strategies were: Encouraging student-student dialogue, making lessons relevant using practical applications, building student self-confidence, and using hands-on inquiry activities. Teachers who incorporate such strategies into their classrooms regardless of the track will likely increase motivation and also enhance learning for all students.

Activation of the TRPV1 Thermoreceptor Induced by Modulated or Unmodulated 1800 MHz Radiofrequency Field Exposure.

PubMed

Ruigrok, Hermanus J; Arnaud-Cormos, Delia; Hurtier, Annabelle; Poque, Emmanuelle; de Gannes, Florence Poulletier; Ruffié, Gilles; Bonnaudin, Fabrice; Lagroye, Isabelle; Sojic, Neso; Arbault, Stéphane; Lévêque, Philippe; Veyret, Bernard; Percherancier, Yann

2018-01-01

The existence of effects of radiofrequency field exposure at environmental levels on living tissues and organisms remains controversial, in particular regarding potential "nonthermal" effects produced in the absence of temperature elevation. Therefore, we investigated whether TRPV1, one of the most studied thermosensitive channels, can be activated by the heat produced by radiofrequency fields and by some specific nonthermal interaction with the fields. We have recently shown that TRPV1 activation can be assessed in real-time on live cells using the bioluminescence resonance energy transfer technique. Taking advantage of this innovative assay, we monitored TRPV1 thermal and chemical modes of activation under radiofrequency exposure at 1800 MHz using different signals (CW, GSM, UMTS, LTE, Wi-Fi and WiMAX) at specific absorption rates between 8 and 32 W/kg. We showed that, as expected, TRPV1 channels were activated by the heat produced by radiofrequency field exposure of transiently-transfected HEK293T cells, but found no evidence of TRPV1 activation in the absence of temperature elevation under radiofrequency field exposure. There was no evidence either that, at fixed temperature, radiofrequency exposure altered the maximal efficacy of the agonist Capsaicin to activate TRPV1.

Lactoferrin from Milk: Nutraceutical and Pharmacological Properties

PubMed Central

Giansanti, Francesco; Panella, Gloria; Leboffe, Loris; Antonini, Giovanni

2016-01-01

Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii) a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article. PMID:27690059

Content-specific activational effects of estrogen on working memory performance.

PubMed

Vranić, Andrea; Hromatko, Ivana

2008-07-01

The authors explored the influence of task content and the menstrual cycle phase on working memory (WM) performance. They addressed the content specificity of WM in the framework of evolutionary psychology, proposing a hormone-mediated adaptive design governing face perception. The authors tested 2 groups of healthy young women (n = 66 women with regular menstrual cycle, n = 27 oral contraceptive users) on a WM task with adult male or infant face photographs. Analyses of variance showed significant interaction between task content and estrogen level. Women were more efficient in solving the male faces task during high-estrogen phase of the cycle than during low-estrogen phase. No differences were found in the efficacy of solving the infant faces task between different phases of the cycle. Results suggest content-specific activational effects of estrogen on the WM performance and are consistent with the notion of a hormonal mechanism underlying adaptive shifts in cognition related to mating motivation.

Immunomodulating activity of Pidotimod in children with Down syndrome.

PubMed

Zuccotti, G V; Mameli, C; Trabattoni, D; Beretta, S; Biasin, M; Guazzarotti, L; Clerici, M

2013-01-01

Acute respiratory tract infections (ARTIs) are the most frequent illnesses in pediatric age, frequently experienced in children with Down Syndrome (DS) due to the associated immune defects of both specific and non-specific immunity. Pidotimod, a synthetic immunostimulant, was shown to reduce the rates of ARTIs in children with DS, however the mechanisms associated with this effect is currently unknown. We analyzed immune parameters in DS children who received the seasonal 2011–2012 virosomal-adjuvanted influenza vaccine. Eighteen children aged 3-10 years (mean age 7.1+/-2.6 years) were randomly assigned (1:1 ratio) to receive Pidotimod 400 mg, administered orally once a day for 90 days or placebo. At the recruitment (T0) all children received a single dose of virosomal-adjuvanted influenza vaccine (Flu). Blood samples were collected at T0 and 3 months after the recruitment (T3) in order to evaluate innate and adaptative immune responses pathway. Flu-specific IgG1 and IgG3 levels in plasma samples were determined at pre-vaccination (T0), and 1 (T1) and 3 months (T3) post-vaccination. The use of Pidotimod was associated with the upregulation of a number of genes involved in the activation of innate immune responses and in antimicrobial activity. Interestingly the ratio of Flu-specific IgG1/IgG3 was skewed in pidotimod-treated individuals, suggesting a preferential activation of complement-dependent effector mechanisms. Although preliminary these data suggest that Pidotimod can potentiate the beneficial effect of immunization, possibly resulting in a stronger activity of both innate and adaptive immune responses.

Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.

PubMed

Jessen, Niels; Pold, Rasmus; Buhl, Esben S; Jensen, Lasse S; Schmitz, Ole; Lund, Sten

2003-04-01

Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.

Intrinsic Network Connectivity Patterns Underlying Specific Dimensions of Impulsiveness in Healthy Young Adults.

PubMed

Kubera, Katharina M; Hirjak, Dusan; Wolf, Nadine D; Sambataro, Fabio; Thomann, Philipp A; Wolf, R Christian

2018-05-01

Impulsiveness is a central human personality trait and of high relevance for the development of several mental disorders. Impulsiveness is a multidimensional construct, yet little is known about dimension-specific neural correlates. Here, we address the question whether motor, attentional and non-planning components, as measured by the Barratt Impulsiveness Scale (BIS-11), are associated with distinct or overlapping neural network activity. In this study, we investigated brain activity at rest and its relationship to distinct dimensions of impulsiveness in 30 healthy young adults (m/f = 13/17; age mean/SD = 26.4/2.6 years) using resting-state functional magnetic resonance imaging at 3T. A spatial independent component analysis and a multivariate model selection strategy were used to identify systems loading on distinct impulsivity domains. We first identified eight networks for which we had a-priori hypotheses. These networks included basal ganglia, cortical motor, cingulate and lateral prefrontal systems. From the eight networks, three were associated with impulsiveness measures (p < 0.05, FDR corrected). There were significant relationships between right frontoparietal network function and all three BIS domains. Striatal and midcingulate network activity was associated with motor impulsiveness only. Within the networks regionally confined effects of age and gender were found. These data suggest distinct and overlapping patterns of neural activity underlying specific dimensions of impulsiveness. Motor impulsiveness appears to be specifically related to striatal and midcingulate network activity, in contrast to a domain-unspecific right frontoparietal system. Effects of age and gender have to be considered in young healthy samples.

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis

PubMed Central

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-01-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced lung fibrosis is diminished in both PAR-1 and PAR-2 deficient mice. We thus have been suggested that combined inactivation of PAR-1 and PAR-2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR-1 and PAR-2 agonists in the absence or presence of specific PAR-1 or PAR-2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and PAR-2 deficient mice with or without a specific PAR-1 antagonist (P1pal-12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR-1 and/or PAR-2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR-1 and PAR-2 did not show any additive effects on these pro-fibrotic responses. Strikingly, PAR-2 deficiency as well as pharmacological PAR-1 inhibition reduced bleomycin-induced pulmonary fibrosis to a similar extent. PAR-1 inhibition in PAR-2 deficient mice did not further diminish bleomycin-induced pulmonary fibrosis. Finally, we show that the PAR-1-dependent pro-fibrotic responses are inhibited by the PAR-2 specific antagonist. Targeting PAR-1 and PAR-2 simultaneously is not superior to targeting either receptor alone in bleomycin-induced pulmonary fibrosis. We postulate that the pro-fibrotic effects of PAR-1 require the presence of PAR-2. PMID:25689283

Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

PubMed

Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

2012-01-01

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Influence of emotional valence and arousal on the spread of activation in memory.

PubMed

Jhean-Larose, Sandra; Leveau, Nicolas; Denhière, Guy

2014-11-01

Controversy still persists on whether emotional valence and arousal influence cognitive activities. Our study sought to compare how these two factors foster the spread of activation within the semantic network. In a lexical decision task, prime words were varied depending on the valence (pleasant or unpleasant) or on the level of emotional arousal (high or low). Target words were carefully selected to avoid semantic priming effects, as well as to avoid arousing specific emotions (neutral). Three SOA durations (220, 420 and 720 ms) were applied across three independent groups. Results indicate that at 220 ms, the effect of arousal is significantly higher than the effect of valence in facilitating spreading activation while at 420 ms, the effect of valence is significantly higher than the effect of arousal in facilitating spreading activation. These findings suggest that affect is a sequential process involving the successive intervention of arousal and valence.

Locomotor activation induced in rodent by substance P and analogues. Blockade of the effect of substance P by met-enkephalin antiserum.

PubMed

Naranjo, J R; Del Rio, J

1984-10-01

Intraventricular administration of substance P (SP), of the heptapeptide SP5-11 and of DiMe-C7, a stable analogue of SP5-11 induced locomotor activation in rats and in mice. The activating effect of substance P was longer-lasting in mice than in rats, whereas the effect of the two heptapeptides appears to be more marked in rats than in mice. The locomotor stimulation induced by substance P was blocked by naloxone and by the specific antiserum against met-enkephalin, suggesting that this effect is possibly mediated by released of this opioid peptide. Since the activating effect of substance P was also blocked by haloperidol, it is proposed that substance P produces behavioural excitation by activating dopaminergic systems, implicated in the control of locomotion, through interposed enkephalinergic neurones.

Chapter 14: Effects of fire suppression and postfire management activities on plant invasions

Treesearch

Matthew L. Brooks

2008-01-01

This chapter explains how various fire suppression and postfire management activities can increase or decrease the potential for plant invasions following fire. A conceptual model is used to summarize the basic processes associated with plant invasions and show how specific fire management activities can be designed to minimize the potential for invasion. The...

School-Based Physical Activity Interventions: Effectiveness, Trends, Issues, Implications and Recommendations for Practice

ERIC Educational Resources Information Center

Cale, Lorraine; Harris, Jo

2006-01-01

The promotion of physical activity within schools and physical education (PE) has attracted growing interest in recent years. Schools have been acknowledged as the primary institution with responsibility for promoting activity in young people and more specifically, school PE has been recognized as having a key role to play. Given this, and based…

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

ERIC Educational Resources Information Center

Randall, Edin T.; Bohnert, Amy M.

2012-01-01

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

Effect of contraceptive steroids on monoamine oxidase activity

PubMed Central

Southgate, Jennifer; Collins, G. G. S.; Pryse-Davies, J.; Sandler, M.

1969-01-01

Cyclical variations in monoamine oxidase activity during the human menstrual cycle, specific to the endometrium and modified in women undergoing contraceptive steroid treatment, may reflect changes in hormonal environment. Treatment of rats with individual constituents of the contraceptive pill causes analogous changes: oestrogens inhibit and progestogens potentiate uterine monoamine oxidase activity. ImagesFig. 2Fig. 3

Effective intracellular inhibition of the cAMP-dependent protein kinase by microinjection of a modified form of the specific inhibitor peptide PKi in living fibroblasts.

PubMed

Fernandez, A; Mery, J; Vandromme, M; Basset, M; Cavadore, J C; Lamb, N J

1991-08-01

In order to obtain a peptide retaining its biological activity following microinjection into living cells, we have modified a synthetic peptide [PKi(m)(6-24)], derived from the specific inhibitor protein of the cAMP-dependent protein kinase (A-kinase) in two ways: (1) substitution of the arginine at position 18 for a D-arginine; (2) blockade of the side chain on the C-terminal aspartic acid by a cyclohexyl ester group. In an in vitro assay, PKi(m) has retained a specific inhibitory activity against A-kinase as assessed against six other kinases, with similar efficiency to that of the unmodified PKi(5-24) peptide. Microinjection of PKi(m) into living fibroblasts reveals its capacity to prevent the changes in cell morphology and cytoskeleton induced by drugs which activate endogenous A-kinase, whereas the original PKi peptide failed to do so. This inhibition of A-kinase in vivo by PKi(m) lasts between 4 and 6 h after injection. In light of its effective half-life, this modified peptide opens a route for the use of biologically active peptides in vivo, an approach which has been hampered until now by the exceedingly short half-life of peptides inside living cells. By providing a direct means of inhibiting A-kinase activity for sufficiently long periods to observe effects on cellular functions in living cells, PKi(m) represents a powerful tool in studying the potential role of cAMP-dependent phosphorylation in vivo.

Education Facilities Sector-Specific Plan: An Annex to the Government Facilities Sector-Specific Plan

ERIC Educational Resources Information Center

US Department of Homeland Security, 2010

2010-01-01

Critical infrastructure and key resources (CIKR) provide the essential services that support basic elements of American society. Compromise of these CIKR could disrupt key government and industry activities, facilities, and systems, producing cascading effects throughout the Nation's economy and society and profoundly affecting the national…

Evaluation of the specificity and effectiveness of selected oral hygiene actives in salivary biofilm microcosms.

PubMed

Ledder, Ruth G; Sreenivasan, Prem K; DeVizio, William; McBain, Andrew J

2010-12-01

The microbiological effects of biocidal products used for the enhancement of oral hygiene relate to the active compound(s) as well as other formulation components. Here, we test the specificities of selected actives in the absence of multiple excipients. Salivary ecosystems were maintained in tissue culture plate-based hydroxyapatite disc models (HDMs) and modified drip-flow biofilm reactors (MDFRs). Test compounds stannous fluoride (SF), SDS, triclosan (TCS), zinc lactate (ZL) and ZL with SF in combination (ZLSF) were delivered to the HDMs once and four times daily for 6 days to MDFRs. Plaques were characterized by differential viable counting and PCR-denaturing gradient gel electrophoresis (DGGE). TCS and SDS were the most effective compounds against HDM plaques, significantly reducing total viable counts (P<0.05), whilst SF, ZL and ZLSF were comparatively ineffective. TCS exhibited specificity for streptococci (P<0.01) and Gram-negative anaerobes (P<0.01) following a single dosing and also on repeated dosing in MDFRs. In contrast to single exposures, multiple dosing with ZLSF also significantly reduced all bacterial groups, whilst SF and ZL caused significant but transient reductions. According to PCR-DGGE analyses, significant (P<0.05) reductions in eubacterial diversity occurred following 6 day dosing with both TCS and ZLSF. Concordance of MDFR eubacterial profiles with salivary inocula ranged between 58 and 97%. TCS and ZL(SF) exhibited similar specificities to those reported for formulations. TCS was the most potent antibacterial, after single and multiple dosage regimens.

Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: effects on energy metabolism.

PubMed

Adzic, Miroslav; Lukic, Iva; Mitic, Milos; Djordjevic, Jelena; Elaković, Ivana; Djordjevic, Ana; Krstic-Demonacos, Marija; Matić, Gordana; Radojcic, Marija

2013-12-01

Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fluoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fluoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

PubMed Central

Haug, Markus; Brede, Gaute; Håkerud, Monika; Nedberg, Anne Grete; Gederaas, Odrun A.; Flo, Trude H.; Edwards, Victoria T.; Selbo, Pål K.; Høgset, Anders; Halaas, Øyvind

2018-01-01

Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs) in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses. PMID:29670624

Metabotropic Glutamate Receptor 5 Activity in the Nucleus Accumbens Is Required for the Maintenance of Ethanol Self-Administration in a Rat Genetic Model of High Alcohol Intake

PubMed Central

Besheer, Joyce; Grondin, Julie J.M.; Cannady, Reginald; Sharko, Amanda C.; Faccidomo, Sara; Hodge, Clyde W.

2010-01-01

Background Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized. This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration. Methods Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration. Results Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity. The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior. Conclusions These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption. PMID:19897175

Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake.

PubMed

Besheer, Joyce; Grondin, Julie J M; Cannady, Reginald; Sharko, Amanda C; Faccidomo, Sara; Hodge, Clyde W

2010-05-01

Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized. This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration. Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration. Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity. The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior. These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

[An experimental study of effects of active-heating-system for extravehicular spacesuit gloves on working performance].

PubMed

Ding, Li; Han, Long-zhu; Yang, Chun-xin; Yang, Feng; Yuan, Xiu-gan

2005-02-01

To observe the effects of active heating system for spacesuit gloves on extravehicular working performance. After analyzing the factors with gloves influence on the working performance, the effects of active heating system for gloves were studied experimentally with aspects to fatigue, hand strength, dexterity and tactile sensing. 1) Heating-system had not influence to grip; 2) Heating-system had 17% influence to fatigue except specific person; 3) Nut assembly and nipping pin showed that heating-system had little influence to dexterity; 4) Apperceiving shape of object and two-point distance showed heating-system had little influence to tactility. The active heating method is rational and has little influence on working performance.

Time course of brain activation elicited by basic emotions.

PubMed

Hot, Pascal; Sequeira, Henrique

2013-11-13

Whereas facial emotion recognition protocols have shown that each discrete emotion has a specific time course of brain activation, there is no electrophysiological evidence to support these findings for emotional induction by complex pictures. Our objective was to specify the differences between the time courses of brain activation elicited by feelings of happiness and, with unpleasant pictures, by feelings of disgust and sadness. We compared event-related potentials (ERPs) elicited by the watching of high-arousing pictures from the International Affective Picture System, selected to induce specific emotions. In addition to a classical arousal effect on late positive components, we found specific ERP patterns for each emotion in early temporal windows (<200 ms). Disgust was the first emotion to be associated with different brain processing after 140 ms, whereas happiness and sadness differed in ERPs elicited at the frontal and central sites after 160 ms. Our findings highlight the limits of the classical averaging of ERPs elicited by different emotions inside the same valence and suggest that each emotion could elicit a specific temporal pattern of brain activation, similar to those observed with emotional face recognition.

Substrate and Enzyme Specificity of the Kinetic Isotope Effects Associated with the Dioxygenation of Nitroaromatic Contaminants.

PubMed

Pati, Sarah G; Kohler, Hans-Peter E; Pabis, Anna; Paneth, Piotr; Parales, Rebecca E; Hofstetter, Thomas B

2016-07-05

Compound-specific isotope analysis (CSIA) is a promising approach for tracking biotransformation of organic pollutants, but isotope fractionation associated with aromatic oxygenations is only poorly understood. We investigated the dioxygenation of a series of nitroaromatic compounds to the corresponding catechols by two enzymes, namely, nitrobenzene and 2-nitrotoluene dioxygenase (NBDO and 2NTDO) to elucidate the enzyme- and substrate-specificity of C and H isotope fractionation. While the apparent (13)C- and (2)H-kinetic isotope effects of nitrobenzene, nitrotoluene isomers, 2,6-dinitrotoluene, and naphthalene dioxygenation by NBDO varied considerably, the correlation of C and H isotope fractionation revealed a common mechanism for nitrobenzene and nitrotoluenes. Similar observations were made for the dioxygenation of these substrates by 2NTDO. Evaluation of reaction kinetics, isotope effects, and commitment-to-catalysis based on experiment and theory showed that rates of dioxygenation are determined by the enzymatic O2 activation and aromatic C oxygenation. The contribution of enzymatic O2 activation to the reaction rate varies for different nitroaromatic substrates of NBDO and 2NTDO. Because aromatic dioxygenation by nonheme iron dioxygenases is frequently the initial step of biodegradation, O2 activation kinetics may also have been responsible for the minor isotope fractionation reported for the oxygenation of other aromatic contaminants.

Keratin sponge/hydrogel II, active agent delivery

USDA-ARS?s Scientific Manuscript database

Keratin sponge/hydrogels from oxidation and reduction hydrolysis of fine and coarse wool fibers were formed to behave as cationic hydrogels to swell and release active agents in the specific region of the gastro-intestinal (GI) tract. Their porous, interpenetrating networks (IPN) were effective for...

Effects of biology teachers' professional knowledge and cognitive activation on students' achievement

NASA Astrophysics Data System (ADS)

Förtsch, Christian; Werner, Sonja; von Kotzebue, Lena; Neuhaus, Birgit J.

2016-11-01

This study examined the effects of teachers' biology-specific dimensions of professional knowledge - pedagogical content knowledge (PCK) and content knowledge (CK) - and cognitively activating biology instruction, as a feature of instructional quality, on students' learning. The sample comprised 39 German secondary school teachers whose lessons on the topic neurobiology were videotaped twice. Teachers' instruction was coded with regard to cognitive activation using a rating manual. Multilevel path analysis results showed a positive significant effect of cognitive activation on students' learning and an indirect effect of teachers' PCK on students' learning mediated through cognitive activation. These findings highlight the importance of PCK in preservice biology teachers' education. Items of the rating manual may be used to provide exemplars of concrete teaching situations during university seminars for preservice teacher education or professional development initiatives for in-service teachers.

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.

PubMed

Sebastián, María; Anoz-Carbonell, Ernesto; Gracia, Begoña; Cossio, Pilar; Aínsa, José Antonio; Lans, Isaías; Medina, Milagros

2018-12-01

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.

Regulation of leukemia-initiating cell activity by the ubiquitin ligase FBXW7

PubMed Central

King, Bryan; Trimarchi, Thomas; Reavie, Linsey; Xu, Luyao; Mullenders, Jasper; Ntziachristos, Panagiotis; Aranda-Orgilles, Beatriz; Perez-Garcia, Arianne; Shi, Junwei; Vakoc, Christopher; Sandy, Peter; Shen, Steven S.; Ferrando, Adolfo; Aifantis, Iannis

2013-01-01

SUMMARY Sequencing efforts led to the identification of somatic mutations that could affect self-renewal and differentiation of cancer-initiating cells. One such recurrent mutation targets the binding pocket of the ubiquitin ligase FBXW7. Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Finally, we demonstrated that small molecule-mediated suppression of MYC activity leads to T-ALL remission, suggesting a novel effective therapeutic strategy. PMID:23791182

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

PubMed

Udi, Shiran; Hinden, Liad; Earley, Brian; Drori, Adi; Reuveni, Noa; Hadar, Rivka; Cinar, Resat; Nemirovski, Alina; Tam, Joseph

2017-12-01

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB 1 R) induces nephropathy, whereas CB 1 R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB 1 R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β -oxidation. Collectively, these findings indicate that renal proximal tubule cell CB 1 R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway. Copyright © 2017 by the American Society of Nephrology.

The Effects of Secondary Oxides on Copper-Based Catalysts for Green Methanol Synthesis.

PubMed

Hayward, James S; Smith, Paul J; Kondrat, Simon A; Bowker, Michael; Hutchings, Graham J

2017-05-10

Catalysts for methanol synthesis from CO 2 and H 2 have been produced by two main methods: co-precipitation and supercritical anti-solvent (SAS) precipitation. These two methods are compared, along with the behaviour of copper supported on Zn, Mg, Mn, and Ce oxides. Although the SAS method produces initially active material with high Cu specific surface area, they appear to be unstable during reaction losing significant amounts of surface area and hence activity. The CuZn catalysts prepared by co-precipitation, however, showed much greater thermal and reactive stability than the other materials. There appeared to be the usual near-linear dependence of activity upon Cu specific area, though the initial performance relationship was different from that post-reaction, after some loss of surface area. The formation of the malachite precursor, as reported before, is important for good activity and stability, whereas if copper oxides are formed during the synthesis and ageing process, then a detrimental effect on these properties is seen.

The Effects of Secondary Oxides on Copper‐Based Catalysts for Green Methanol Synthesis

PubMed Central

Hayward, James S.; Smith, Paul J.; Kondrat, Simon A.; Bowker, Michael

2017-01-01

Abstract Catalysts for methanol synthesis from CO2 and H2 have been produced by two main methods: co‐precipitation and supercritical anti‐solvent (SAS) precipitation. These two methods are compared, along with the behaviour of copper supported on Zn, Mg, Mn, and Ce oxides. Although the SAS method produces initially active material with high Cu specific surface area, they appear to be unstable during reaction losing significant amounts of surface area and hence activity. The CuZn catalysts prepared by co‐precipitation, however, showed much greater thermal and reactive stability than the other materials. There appeared to be the usual near‐linear dependence of activity upon Cu specific area, though the initial performance relationship was different from that post‐reaction, after some loss of surface area. The formation of the malachite precursor, as reported before, is important for good activity and stability, whereas if copper oxides are formed during the synthesis and ageing process, then a detrimental effect on these properties is seen. PMID:28706570

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem.

PubMed

Kišidayová, Svetlana; Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities.

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem

PubMed Central

Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities. PMID:29324899

Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials.

PubMed

Yardimci, Mustafa; Sevgiler, Yusuf; Rencuzogullari, Eyyup; Arslan, Mehmet; Buyukleyla, Mehmet; Yilmaz, Mehmet

2014-12-01

Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid's adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg⁻¹) or in combination with piperonyl butoxide (100 mg kg⁻¹) or menadione (25 mg kg⁻¹) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity.

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.

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

Muscle Activation During ACL Injury Risk Movements in Young Female Athletes: A Narrative Review.

PubMed

Bencke, Jesper; Aagaard, Per; Zebis, Mette K

2018-01-01

Young, adolescent female athletes are at particular high risk of sustaining a non-contact anterior cruciate ligament (ACL) injury during sport. Through the last decades much attention has been directed toward various anatomical and biomechanical risk factors for non-contact ACL injury, and important information have been retrieved about the influence of external loading factors on ACL injury risk during given sports-specific movements. However, much less attention has been given to the aspect of neuromuscular control during such movements and only sparse knowledge exists on the specific muscle activation patterns involved during specific risk conditions. Therefore, the aim of this narrative review was (1) to describe anatomical aspects, strength aspects and biomechanical aspects relevant for the understanding of ACL non-contact injury mechanisms in young female athletes, and (2) to review the existing literature on lower limb muscle activation in relation to risk of non-contact ACL-injury and prevention of ACL injury in young female athletes. Studies investigating muscle activity patterns associated with sports-specific risk situations were identified, comprising cohort studies, intervention studies and prospective studies. Based on the retrieved studies, clear gender-specific differences in muscle activation and coordination were identified demonstrating elevated quadriceps activity and reduced hamstring activity in young female athletes compared to their male counterparts, and suggesting young female athletes to be at elevated risk of non-contact ACL injury. Only few studies ( n = 6) examined the effect of preventive exercise-based intervention protocols on lower limb muscle activation during sports-specific movements. A general trend toward enhanced hamstring activation was observed during selected injury risk situations (e.g., sidecutting and drop landings). Only a single study examined the association between muscle activation deficits and ACL injury risk, reporting that low medial hamstring activation and high vastus lateralis activation prior to landing was associated with an elevated incidence of ACL-injury. A majority of studies were performed in adult female athletes. The striking paucity of studies in adolescent female athletes emphasizes the need for increased research activities to examine of lower limb muscle activity in relation to non-contact ACL injury in this high-risk athlete population.

NF-κB Activation Protects Oligodendrocytes against Inflammation

PubMed Central

Stone, Sarrabeth; Jamison, Stephanie; Yue, Yuan; Durose, Wilaiwan

2017-01-01

NF-κB is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-κB activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IκBαΔN, a super-suppressor of NF-κB, specifically in oligodendrocytes and demonstrated that IκBαΔN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IκBαΔN blocked NF-κB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that express IFN-γ ectopically in the CNS (both sexes). We also showed that NF-κB inactivation in oligodendrocytes aggravated IFN-γ-induced remyelinating oligodendrocyte death and remyelination failure in the cuprizone model (male mice). Moreover, we found that NF-κB inactivation in oligodendrocytes increased the susceptibility of mice to EAE (female mice). These findings imply the cytoprotective effects of NF-κB activation on oligodendrocytes in MS and EAE. SIGNIFICANCE STATEMENT Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. NF-κB is a major player in inflammatory diseases that acts by regulating inflammation and cell viability. Data indicate that NF-κB activation in inflammatory cells facilitates the development of MS. However, to date, attempts to understand the role of NF-κB activation in oligodendrocytes in MS have been unsuccessful. Herein, we generated a mouse model that allows for inactivation of NF-κB specifically in oligodendrocytes and then used this model to determine the precise role of NF-κB activation in oligodendrocytes in models of MS. The results presented in this study represent the first demonstration that NF-κB activation acts cell autonomously to protect oligodendrocytes against inflammation in animal models of MS. PMID:28842413

[Effect of age, different light conditions, melatonin, and epitalon on lysosomal proteinase activity in the liver and kidneys of rats].

PubMed

Rendakov, N L; Tiutiunnik, N N; Vinogradova, I A

2006-01-01

Ageing, melatonin, epithalon (tetrapeptide Ala-Glu-Asp-Gly) and different light conditions effects on protein content and cathepsins B and D activities in rat liver and kidneys lysosomal fractions were studied. Ageing leads to decrease of cathepsins activity in rat liver lysosomal fractions. Constant light and darkness conditions result in earlier age decline of cathepsins activity. Absence of day and night succession in comparison with alternating light conditions causes decline of both general and specific cathepsin D activity. Melatonin and epithalon administration resulted in decrease of cathepsin D activity in liver only under control interchangeable light conditions. Cathepsin B activity in liver and kidneys lysosomal fractions declined in all experimental light conditions. Cathepsins activity decrease under the influence of epiphysial factors is evidently connected with their inhibitory effect on protein and general metabolism.

Potential for thermal tolerance to mediate climate change effects on three members of a cool temperate lizard genus, Niveoscincus.

PubMed

Caldwell, Amanda J; While, Geoffrey M; Beeton, Nicholas J; Wapstra, Erik

2015-08-01

Climatic changes are predicted to be greater in higher latitude and mountainous regions but species specific impacts are difficult to predict. This is partly due to inter-specific variance in the physiological traits which mediate environmental temperature effects at the organismal level. We examined variation in the critical thermal minimum (CTmin), critical thermal maximum (CTmax) and evaporative water loss rates (EWL) of a widespread lowland (Niveoscincus ocellatus) and two range restricted highland (N. microlepidotus and N. greeni) members of a cool temperate Tasmanian lizard genus. The widespread lowland species had significantly higher CTmin and CTmax and significantly lower EWL than both highland species. Implications of inter-specific variation in thermal tolerance for activity were examined under contemporary and future climate change scenarios. Instances of air temperatures below CTmin were predicted to decline in frequency for the widespread lowland and both highland species. Air temperatures of high altitude sites were not predicted to exceed the CTmax of either highland species throughout the 21st century. In contrast, the widespread lowland species is predicted to experience air temperatures in excess of CTmax on 1 or 2 days by three of six global circulation models from 2068-2096. To estimate climate change effects on activity we reran the thermal tolerance models using minimum and maximum temperatures selected for activity. A net gain in available activity time was predicted under climate change for all three species; while air temperatures were predicted to exceed maximum temperatures selected for activity with increasing frequency, the change was not as great as the predicted decline in air temperatures below minimum temperatures selected for activity. We hypothesise that the major effect of rising air temperatures under climate change is an increase in available activity period for both the widespread lowland and highland species. The consequences of a greater available activity period will depend on the extent to which changes in climate alters other related factors, such as the nature and level of competition between the respective species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fibrin-specific and effective clot lysis requires both plasminogen activators and for them to be in a sequential rather than simultaneous combination.

PubMed

Pannell, R; Li, S; Gurewich, V

2017-08-01

Thrombolysis with tissue plasminogen activator (tPA) has been a disappointment and has now been replaced by an endovascular procedure whenever possible. Nevertheless, thrombolysis remains the only means by which circulation in a thrombosed artery can be restored rapidly. In contrast to tPA monotherapy, endogenous fibrinolysis uses both tPA and urokinase plasminogen activator (uPA), whose native form is a proenzyme, prouPA. This combination is remarkably effective as evidenced by the fibrin degradation product, D-dimer, which is invariably present in plasma. The two activators have complementary mechanisms of plasminogen activation and are synergistic in combination. Since tPA initiates fibrinolysis when released from the vessel wall and prouPA is in the blood, they induce fibrinolysis sequentially. It was postulated that this may be more effective and fibrin-specific. The hypothesis was tested in a model of clot lysis in plasma in which a clot was first exposed to tPA for 5 min, washed and incubated with prouPA. Lysis was compared with that of clots incubated with both activators simultaneously. The sequential combination was almost twice as effective and caused less fibrinogenolysis than the simultaneous combination (p < 0.0001) despite having significantly less tPA, as a result of the wash. A mechanism is described by which this phenomenon can be explained. The findings are believed to have significant therapeutic implications.

Feasibility and Effectiveness of Using Wearable Activity Trackers in Youth: A Systematic Review

PubMed Central

McNarry, Melitta A; Mackintosh, Kelly A

2016-01-01

Background The proliferation and popularity of wearable activity trackers (eg, Fitbit, Jawbone, Misfit) may present an opportunity to integrate such technology into physical activity interventions. While several systematic reviews have reported intervention effects of using wearable activity trackers on adults’ physical activity levels, none to date have focused specifically on children and adolescents. Objective The aim of this review was to examine the effectiveness of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. We also examined the feasibility of using such technology in younger populations (age range 5-19 years). Methods We conducted a systematic search of 5 electronic databases, reference lists, and personal archives to identify articles published up until August 2016 that met the inclusion criteria. Articles were included if they (1) specifically examined the use of a wearable device within an intervention or a feasibility study; (2) included participants aged 5-19 years old; (3) had a measure of physical activity as an outcome variable for intervention studies; (4) reported process data concerning the feasibility of the device in feasibility studies; and (5) were published in English. Data were analyzed in August 2016. Results In total, we identified and analyzed 5 studies (3 intervention, 2 feasibility). Intervention delivery ranged from 19 days to 3 months, with only 1 study using a randomized controlled trial design. Wearable activity trackers were typically combined with other intervention approaches such as goal setting and researcher feedback. While intervention effects were generally positive, the reported differences were largely nonsignificant. The feasibility studies indicated that monitor comfort and design and feedback features were important factors to children and adolescents. Conclusions There is a paucity of research concerning the effectiveness and feasibility of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. While there are some preliminary data to suggest these devices may have the potential to increase activity levels through self-monitoring and goal setting in the short term, more research is needed to establish longer-term effects on behavior. PMID:27881359

ERP correlates of anticipatory attention: spatial and non-spatial specificity and relation to subsequent selective attention.

PubMed

Dale, Corby L; Simpson, Gregory V; Foxe, John J; Luks, Tracy L; Worden, Michael S

2008-06-01

Brain-based models of visual attention hypothesize that attention-related benefits afforded to imperative stimuli occur via enhancement of neural activity associated with relevant spatial and non-spatial features. When relevant information is available in advance of a stimulus, anticipatory deployment processes are likely to facilitate allocation of attention to stimulus properties prior to its arrival. The current study recorded EEG from humans during a centrally-cued covert attention task. Cues indicated relevance of left or right visual field locations for an upcoming motion or orientation discrimination. During a 1 s delay between cue and S2, multiple attention-related events occurred at frontal, parietal and occipital electrode sites. Differences in anticipatory activity associated with the non-spatial task properties were found late in the delay, while spatially-specific modulation of activity occurred during both early and late periods and continued during S2 processing. The magnitude of anticipatory activity preceding the S2 at frontal scalp sites (and not occipital) was predictive of the magnitude of subsequent selective attention effects on the S2 event-related potentials observed at occipital electrodes. Results support the existence of multiple anticipatory attention-related processes, some with differing specificity for spatial and non-spatial task properties, and the hypothesis that levels of activity in anterior areas are important for effective control of subsequent S2 selective attention.

Superior In Vitro Stimulation of Human CD8+ T-Cells by Whole Virus versus Split Virus Influenza Vaccines

PubMed Central

Distler, Eva; Dass, Martin; Wagner, Eva M.; Plachter, Bodo; Probst, Hans Christian; Strand, Dennis; Hartwig, Udo F.; Karner, Anita; Aichinger, Gerald; Kistner, Otfried; Landfester, Katharina; Herr, Wolfgang

2014-01-01

Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations. PMID:25072749

Effects of addition of different carbon materials on the electrochemical performance of nickel hydroxide electrode

NASA Astrophysics Data System (ADS)

Sierczynska, Agnieszka; Lota, Katarzyna; Lota, Grzegorz

Nickel hydroxide is used as an active material in positive electrodes of rechargeable alkaline batteries. The capacity of nickel-metal hydride (Ni-MH) batteries depends on the specific capacity of the positive electrode and utilization of the active material because of the Ni(OH) 2/NiOOH electrode capacity limitation. The practical capacity of the positive nickel electrode depends on the efficiency of the conductive network connecting the Ni(OH) 2 particle with the current collector. As β-Ni(OH) 2 is a kind of semiconductor, the additives are necessary to improve the conductivity between the active material and the current collector. In this study the effect of adding different carbon materials (flake graphite, multi-walled carbon nanotubes (MWNT)) on the electrochemical performance of pasted nickel-foam electrode was established. A method of production of MWNT special type of catalysts had an influence on the performance of the nickel electrodes. The electrochemical tests showed that the electrode with added MWNT (110-170 nm diameter) exhibited better electrochemical properties in the chargeability, specific discharge capacity, active material utilization, discharge voltage and cycling stability. The nickel electrodes with MWNT addition (110-170 nm diameter) have exhibited a specific capacity close to 280 mAh g -1 of Ni(OH) 2, and the degree of active material utilization was ∼96%.

Knee joint stabilization therapy in patients with osteoarthritis of the knee: a randomized, controlled trial.

PubMed

Knoop, J; Dekker, J; van der Leeden, M; van der Esch, M; Thorstensson, C A; Gerritsen, M; Voorneman, R E; Peter, W F; de Rooij, M; Romviel, S; Lems, W F; Roorda, L D; Steultjens, M P M

2013-08-01

To investigate whether an exercise program, initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only, in reducing activity limitations in patients with knee osteoarthritis (OA) and instability of the knee joint. A single-blind, randomized, controlled trial involving 159 knee OA patients with self-reported and/or biomechanically assessed knee instability, randomly assigned to two treatment groups. Both groups received a supervised exercise program for 12 weeks, consisting of muscle strengthening exercises and training of daily activities, but only in the experimental group specific knee joint stabilization training was provided. Outcome measures included activity limitations (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC physical function, primary outcome), pain, global perceived effect and knee stability. Both treatment groups demonstrated large (∼20-40%) and clinically relevant reductions in activity limitations, pain and knee instability, which were sustained 6 months post-treatment. No differences in effectiveness between experimental and control treatment were found on WOMAC physical function (B (95% confidence interval - CI) = -0.01 (-2.58 to 2.57)) or secondary outcome measures, except for a higher global perceived effect in the experimental group (P = 0.04). Both exercise programs were highly effective in reducing activity limitations and pain and restoring knee stability in knee OA patients with instability of the knee. In knee OA patients suffering from knee instability, specific knee joint stabilization training, in addition to muscle strengthening and functional exercises, does not seem to have any additional value. Dutch Trial Register (NTR) registration number: NTR1475. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A regulator of ubiquitin-proteasome activity, 2-hexyldecanol, suppresses melanin synthesis and the appearance of facial hyperpigmented spots.

PubMed

Hakozaki, T; Laughlin, T; Zhao, S; Wang, J; Deng, D; Jewell-Motz, E; Elstun, L

2013-07-01

2-Hexyldecanol has long been used in skin-care products, but has not previously been reported as an active ingredient for skin benefits. To evaluate 2-hexyldecanol in in vitro and ex vivo systems and, if found to be active, progress it to topical clinical testing to determine effects on pigmentation in skin. 2-Hexyldecanol was tested in melanocyte cell culture systems (B16 mouse melanoma cells and normal human melanocytes) for its effect on proteolytic activity and melanin production, in the absence and presence of the proteasome-specific inhibitor, MG132. It was further tested in a human skin explant model for its effect on melanin production. Lastly, topically applied 2-hexyldecanol was evaluated for its effect on the appearance of facial pigmentation in an 8-week, randomized, double-blind, vehicle-controlled, split-face incomplete block design study in Chinese women. In submerged cell culture, 2-hexyldecanol upregulated proteolytic activity and decreased melanin synthesis. These effects were antagonized by the proteasome-specific inhibitor MG132. MG132, tested in the absence of 2-hexyldecanol, increased melanin production. In a human skin explant model, topical 2-hexyldecanol suppressed the production of melanin vs. a vehicle control. In a human clinical study in Chinese women (n = 110 observations per test material), a 2-hexyldecanol-containing formulation significantly reduced the appearance of facial hyperpigmented spots vs. its control. These data indicate that regulation of proteasome activity is a viable target for control of melanin production, that 2-hexyldecanol upregulates proteasomal activity in melanocytes, and that topical 2-hexyldecanol reduces the appearance of hyperpigmentation. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Effect of calcination temperatures on microstructures and photocatalytic activity of tungsten trioxide hollow microspheres.

PubMed

Yu, Jiaguo; Qi, Lifang; Cheng, Bei; Zhao, Xiufeng

2008-12-30

Tungsten trioxide hollow microspheres were prepared by immersing SrWO4 microspheres in a concentrated HNO3 solution, and then calcined at different temperatures. The prepared tungsten oxide samples were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectra, differential thermal analysis-thermogravimetry, UV-visible spectrophotometry, scanning electron microscopy, N2 adsorption/desorption measurements. The photocatalytic activity of the samples was evaluated by photocatalytic decolorization of rhodamine B aqueous solution under visible-light irradiation. It was found that with increasing calcination temperatures, the average crystallite size and average pore size increased, on the contrary, Brunauer-Emmett-Teller-specific surface areas decreased. However, pore volume and porosity increased firstly, and then decreased. Increasing calcination temperatures resulted in the changes of surface morphology of hollow microspheres. The un-calcined and 300 degrees C-calcined samples showed higher photocatalytic activity than other samples. At 400 degrees C, the photocatalytic activity decreased greatly due to the decrease of specific surface areas. At 500 degrees C, the photocatalytic activity of the samples increased again due to the junction effect of two phases.

Insulin Action is Blocked by a Monoclonal Antibody That Inhibits the Insulin Receptor Kinase

NASA Astrophysics Data System (ADS)

Morgan, David O.; Ho, Lisa; Korn, Laurence J.; Roth, Richard A.

1986-01-01

Thirty-six monoclonal antibodies to the human insulin receptor were produced. Thirty-four bound the intracellular domain of the receptor β subunit, the domain containing the tyrosine-specific kinase activity. Of these 34 antibodies, 33 recognized the rat receptor and 1 was shown to precipitate the receptors from mice, chickens, and frogs with high affinity. Another of the antibodies inhibited the kinase activities of the human and frog receptors with equal potencies. This antibody inhibited the kinase activities of these receptors by more than 90%, whereas others had no effect on either kinase activity. Microinjection of the inhibiting antibody into Xenopus oocytes blocked the ability of insulin to stimulate oocyte maturation. In contrast, this inhibiting antibody did not block the ability of progesterone to stimulate the same response. Furthermore, control immunoglobulin and a noninhibiting antibody to the receptor β subunit did not block this response to insulin. These results strongly support a role for the tyrosine-specific kinase activity of the insulin receptor in mediating this biological effect of insulin.

Specificity and mechanism of protein kinase C activation by sn-1,2-diacylglycerols.

PubMed Central

Ganong, B R; Loomis, C R; Hannun, Y A; Bell, R M

1986-01-01

The specificity of protein kinase C activation by sn-1,2-diacylglycerols and analogues was investigated by using a Triton X-100 mixed micellar assay [Hannun, Y. A., Loomis, C. R. & Bell, R. M. (1985) J. Biol. Chem. 260, 10039-10043]. Analogues containing acyl or alkyl chains eight carbons in length were synthesized because sn-1,2-dioctanoylglycerol is an effective cell-permeant activator of protein kinase C. These analogues were tested as activators and antagonists of rat brain protein kinase C to determine the exact structural features important for activity. The analogues established that activation of protein kinase C by diacylglycerols is highly specific. Several analogues established that both carbonyl moieties of the oxygen esters are required for maximal activity and that the 3-hydroxyl moiety is also required. None of the analogues were antagonists. These data, combined with previous investigations, permitted formulation of a model of protein kinase C activation. A three-point attachment of sn-1,2-diacylglycerol to the surface-bound protein kinase C-phosphatidylserine-Ca2+ complex is envisioned to cause activation. Direct ligation of diacylglycerol to Ca2+ is proposed to be an essential step in the mechanism of activation of protein kinase C. Images PMID:3456578

Porous carbon from local coconut shell char by CO2 and H2O activation in the presence of K2CO3

NASA Astrophysics Data System (ADS)

Vi, Nguyen Ngoc Thuy; Truyen, Dang Hai; Trung, Bien Cong; An, Ngo Thanh; Van Dung, Nguyen; Long, Nguyen Quang

2017-09-01

Vietnamese coconut shell char was activated by steam and carbon dioxide at low temperatures with the presence of K2CO3 as a catalyst. The effects of process parameters on adsorption capability of the product including different ratio of impregnation of activation agents, activation temperature, activation time were investigated in this study. Iodine number, methylene blue adsorption capacity, specific surface area and pore size distribution were measured to assess the properties of the activated carbon. Accordingly, the porous carbon was applied for toluene removal by adsorption technology. Significant increases in specific surface area and the toluene adsorption capacity were observed when the coconut shell char was activated in CO2 flow at 720 °C for 150 minutes and the K2CO3/char weight ratio of 0.5.

The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1

PubMed Central

Raoch, V; Martinez-Miguel, P; Arribas-Gomez, I; Rodriguez-Puyol, M; Rodriguez-Puyol, D; Lopez-Ongil, S

2007-01-01

Background and purpose: CGS-26303 inhibits endothelin converting enzyme (ECE)-1 more specifically than phosphoramidon. We have studied the effect of CGS-26303 on ECE-1 expression in bovine aortic endothelial cells. Methods: ECE-1 activity and big endothelin (ET)-1 levels were measured by ELISA, ECE-1 expression using western and northern blot and promoter activity using transfection assays. Key results: ECE-1 activity was completely inhibited by CGS-26303 25 μ M and phosphoramidon 100 μ M. CGS-26303 and phosphoramidon, though not thiorphan, a neutral endopeptidase (NEP) inhibitor, stimulated ECE-1 expression in cells (maximal effect at 16 h, 25 μ M). Cycloheximide abolished that effect. CGS-26303 induced ECE-1 mRNA expression and ECE-1 promoter activity. CGS-35066, a selective ECE-1 inhibitor, mimicked the effects of CGS-26303, suggesting that the effect was specific to ECE-1 inhibition. Big ET-1 accumulated in the cells and in the supernatants after CGS-26303 treatment. Neither exogenously added ET-1 nor the blockade of their receptors with bosentan modified ECE-1 protein. When big ET-1 was added to cells, significant increases in ECE-1 protein content and ECE-1 promoter activity were found. Bosentan did not block those effects. CGS-26303 did not modify prepro-ET-1 expression. CGS-26303 and big ET-1 induced the same effects in human endothelial cells, at lower doses. Conclusions: These results suggest that the accumulation of big ET-1 is responsible for the effects of CGS-26303 on ECE-1 and they did not depend on NEP blockade. Changes in ECE-1 protein after the administration of CGS-26303 could lead to a decreased response in long-term treatments. PMID:17643133

Effects of pore structure and electrolyte on the capacitive characteristics of steam- and KOH-activated carbons for supercapacitors

NASA Astrophysics Data System (ADS)

Wu, Feng-Chin; Tseng, Ru-Ling; Hu, Chi-Chang; Wang, Chen-Ching

Four kinds of activated carbons (denoted as ACs) with specific surface area of ca. 1050 m 2 g -1 were fabricated from fir wood and pistachio shell by means of steam activation or chemical activation with KOH. Pore structures of ACs were characterized by a t-plot method based on N 2 adsorption isotherms. The amount of mesopores within KOH-activated carbons ranged from 9.2 to 15.3% while 33.3-49.5% of mesopores were obtained for the steam-activated carbons. The pore structure, surface functional groups, and raw materials of ACs, as well as pH and the supporting electrolyte were also found to be significant factors determining the capacitive characteristics of ACs. The excellent capacitive characteristics in both acidic and neutral media and the weak dependence of the specific capacitance on the scan rate of cyclic voltammetry (CV) for the ACs derived from the pistachio shell with steam activation (denoted as P-H 2O-AC) revealed their promising potential in the application of supercapacitors. The ACs derived from fir wood with KOH activation (denoted as F-KOH-AC), on the other hand, showed the best capacitive performance in H 2SO 4 due to excellent reversibility and high specific capacitance (180 F g -1 measured at 10 mV s -1), which is obviously larger than 100 F g -1 (a typical value of activated carbons with specific surface areas equal to/above 1000 m 2 g -1).

Stretch and interleukin 1 beta: pro-labour factors with similar mitogen-activated protein kinase effects but differential patterns of transcription factor activation and gene expression.

PubMed

Sooranna, S R; Engineer, N; Liang, Z; Bennett, P R; Johnson, M R

2007-07-01

IL-1beta and stretch increase uterine smooth muscle cell (USMC) prostaglandin H synthase 2 (PGHS-2) and interleukin (IL)-8 mRNA expression in a mitogen-activated protein kinase (MAPK) dependent mechanism. We have tested our hypothesis that stretch and IL-1beta activate different components of the MAPK cascade in USMC and investigated the effects of specific MAPK inhibitors on these components. Further, we have used a Jun N-terminal kinase (JNK) and p38 activator, anisomycin, to compare the effect of differential MAPK activation on the expression of PGHS-2, IL-8 and oxytocin receptor (OTR) mRNA with that seen in response to stretch and IL-1beta. Stretch, IL-1beta and anisomycin activated similar components of the MAPK cascade and specific inhibitors of MAPK altered phosphorylation of MAPK and downstream cascade components as expected. Expression of OTR mRNA was increased by stretch and anisomycin in a MAPK-independent manner. All three stimuli increased PGHS-2 and IL-8 mRNA expression in a MAPK-dependent manner, but while the MAPK inhibitors reduced the IL-1beta-induced activation of activating transcription factor (ATF)-2, liver activating protein (LAP) and c-jun, the stretch-induced increase in LAP was unaffected by MAPK-inhibition and only JNK inhibition appeared to reduce c-jun activation. These observations show that stretch, IL-1beta and anisomycin activate the same components of the MAPK cascade, but differentially activate LAP and liver inhibitory protein (LIP) perhaps accounting for the increase in OTR by stretch and anisomycin but not IL-1beta observed in this study.

Differential patterns of amygdala and ventral striatum activation predict gender-specific changes in sexual risk behavior.

PubMed

Victor, Elizabeth C; Sansosti, Alexandra A; Bowman, Hilary C; Hariri, Ahmad R

2015-06-10

Although the initiation of sexual behavior is common among adolescents and young adults, some individuals express this behavior in a manner that significantly increases their risk for negative outcomes including sexually transmitted infections. Based on accumulating evidence, we have hypothesized that increased sexual risk behavior reflects, in part, an imbalance between neural circuits mediating approach and avoidance in particular as manifest by relatively increased ventral striatum (VS) activity and relatively decreased amygdala activity. Here, we test our hypothesis using data from seventy 18- to 22-year-old university students participating in the Duke Neurogenetics Study. We found a significant three-way interaction between amygdala activation, VS activation, and gender predicting changes in the number of sexual partners over time. Although relatively increased VS activation predicted greater increases in sexual partners for both men and women, the effect in men was contingent on the presence of relatively decreased amygdala activation and the effect in women was contingent on the presence of relatively increased amygdala activation. These findings suggest unique gender differences in how complex interactions between neural circuit function contributing to approach and avoidance may be expressed as sexual risk behavior in young adults. As such, our findings have the potential to inform the development of novel, gender-specific strategies that may be more effective at curtailing sexual risk behavior. Copyright © 2015 the authors 0270-6474/15/358896-05$15.00/0.

Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross-sectional study on effects of time since injury and physical activity level.

PubMed

de Groot, Sonja; van der Scheer, Jan W; Bakkum, Arjan J T; Adriaansen, Jacinthe J E; Smit, Christof A; Dijkstra, Catja; Post, Marcel W M; van der Woude, Lucas H V

2016-01-01

To study the impact of time since injury (TSI) and physical activity (PA) on fitness of persons with spinal cord injury (SCI). Cross-sectional study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and ≥30 years after SCI and divided in an active and inactive group. Fitness [peak power output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. In persons with tetraplegia, no significant relationship was found between TSI and fitness after controlling for confounders, while a higher activity level was related to a higher POpeak in this group. Active people with tetraplegia also showed less decline in POpeak with an increase in TSI compared to inactive people. In persons with paraplegia, after controlling for confounders, it was shown that TSI had a negative effect on POpeak, while PA was not significantly associated with fitness in people with paraplegia. In people with paraplegia, fitness was significantly lower in those with a longer TSI. Persons with a long TSI might need more attention to remain fit and PA might be an important element in that respect as shown by the results of the group with a tetraplegia. Wheelchair-specific fitness seems to diminish over time after paraplegia. An active lifestyle is related to wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term deconditioning is very important.

Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines

PubMed Central

Chang, Wei-Ting; Chen, Hui-Ming; Yin, Shu-Yi; Chen, Yung-Hsiang; Wen, Chih-Chun; Wei, Wen-Chi; Lai, Phoency; Wang, Cheng-Hsin; Yang, Ning-Sun

2013-01-01

Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines. PMID:23935688

Caveolae-localized L-type Ca2+ channels do not contribute to function or hypertrophic signalling in the mouse heart.

PubMed

Correll, Robert N; Makarewich, Catherine A; Zhang, Hongyu; Zhang, Chen; Sargent, Michelle A; York, Allen J; Berretta, Remus M; Chen, Xiongwen; Houser, Steven R; Molkentin, Jeffery D

2017-06-01

L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t-tubules where they initiate excitation-contraction coupling. Our recent work has shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae of adult feline cardiomyocytes can also generate a Ca2+ microdomain that activates nuclear factor of activated T-cells signaling and cardiac hypertrophy, although the relevance of this paradigm to hypertrophy regulation in vivo has not been examined. Here we generated heart-specific transgenic mice with a putative caveolae-targeted LTCC activator protein that was ineffective in initiating or enhancing cardiac hypertrophy in vivo. We also generated transgenic mice with cardiac-specific overexpression of a putative caveolae-targeted inhibitor of LTCCs, and while this protein inhibited caveolae-localized LTCCs without effects on global Ca2+ handling, it similarly had no effect on cardiac hypertrophy in vivo. Cardiac hypertrophy was elicited by pressure overload for 2 or 12 weeks or with neurohumoral agonist infusion. Caveolae-specific LTCC activator or inhibitor transgenic mice showed no greater change in nuclear factor of activated T-cells activity after 2 weeks of pressure overload stimulation compared with control mice. Our results indicate that LTCCs in the caveolae microdomain do not affect cardiac function and are not necessary for the regulation of hypertrophic signaling in the adult mouse heart. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

A dynamic model for generating actuator specifications for small arms barrel active stabilization

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan; Lavigna, Chris

2006-03-01

Due to stresses encountered in combat, it is known that soldier marksmanship noticeably decreases regardless of prior training. Active stabilization systems in small arms have potential to address this problem to increase soldier survivability and mission effectiveness. The key to success is proper actuator design, but this is highly dependent on proper specification which is challenging due to the human/weapon interaction. This paper presents a generic analytical dynamic model which is capable of defining the necessary actuation specifications for a wide range of small arms platforms. The model is unique because it captures the human interface--shoulder and arm--that introduces the jitter disturbance in addition to the geometry, inertial properties and active stabilization stiffness of the small arms platform. Because no data to date is available for actual shooter-induced disturbance in field conditions, a method is given using the model to back-solve from measured shooting range variability data the disturbance amplitude information relative to the input source (arm or shoulder). As examples of the applicability of the model to various small arms systems, two different weapon systems were investigated: the M24 sniper weapon and the M16 assault rifle. In both cases, model based simulations provided valuable insight into impact on the actuation specifications (force, displacement, phase, frequency) due to the interplay of the human-weapon-active stabilization interface including the effect of shooter-disturbance frequency, disturbance location (shoulder vs. arm), and system parameters (stiffness, barrel rotation).

Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

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

Fan, Yu; Zhan, Qian; Xu, Hongying

The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect onmore » Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.« less

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats.

PubMed

Ellis, J R; McDonald, R B; Stern, J S

1990-01-01

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.

Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis.

PubMed

Hylander, Terese; Latif, Leith; Petersson-Westin, Ulla; Cardell, Lars Olaf

2013-02-01

Allergen-specific immunotherapy is the only causative treatment of IgE-mediated allergic disorders. The most common administration route is subcutaneous, which may necessitate more than 50 allergen injections during 3 to 5 years. Recent evidence suggests that direct intralymphatic injections could yield faster beneficial results with considerably lower allergen doses and markedly reduced numbers of injections. To evaluate the effects of intralymphatic allergen-specific immunotherapy in pollen-allergic patients. In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with allergic rhinitis were treated with 3 intralymphatic inguinal injections of ALK Alutard (containing 1000 SQ-U birch pollen or grass pollen) or placebo (ALK diluent). Clinical pre- and posttreatment parameters were assessed, the inflammatory cell content in nasal lavage fluids estimated, and the activation pattern of peripheral T cells described. All patients tolerated the intralymphatic immunotherapy (ILIT) treatment well, and the injections did not elicit any severe adverse event. Patients receiving active treatment displayed an initial increase in allergen-specific IgE level and peripheral T-cell activation. A clinical improvement in nasal allergic symptoms upon challenge was recorded along with a decreased inflammatory response in the nose. In addition, these patients reported an improvement in their seasonal allergic disease. No such changes were seen in the placebo group. Although this study is based on a limited number of patients, ILIT with grass-pollen or birch-pollen extracts appears to reduce nasal allergic symptoms without causing any safety problems. Hence, ILIT might constitute a less time-consuming and more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Variation effect on the insecticide activity of DDT analogues. A chemometric approach

NASA Astrophysics Data System (ADS)

Itoh, S.; Nagashima, U.

2002-08-01

We investigated a variation effect on the insecticide activity of DDT analogues by using the first principles electronic structure calculations and the neural network analysis. It has been found that the charge distribution at the specific atomic sites in the DDT molecule is related to their toxicity. This approach can contribute to designing a new insecticide and a new harmlessness process of the DDT analogues.

Effects of yoga on brain waves and structural activation: A review.

PubMed

Desai, Radhika; Tailor, Anisha; Bhatt, Tanvi

2015-05-01

Previous research has shown the vast mental and physical health benefits associated with yoga. Yoga practice can be divided into subcategories that include posture-holding exercise (asana), breathing (pranayama, Kriya), and meditation (Sahaj) practice. Studies measuring mental health outcomes have shown decreases in anxiety, and increases in cognitive performance after yoga interventions. Similar studies have also shown cognitive advantages amongst yoga practitioners versus non-practitioners. The mental health and cognitive benefits of yoga are evident, but the physiological and structural changes in the brain that lead to this remain a topic that lacks consensus. Therefore, the purpose of this study was to examine and review existing literature on the effects of yoga on brain waves and structural changes and activation. After a narrowed search through a set of specific inclusion and exclusion criteria, 15 articles were used in this review. It was concluded that breathing, meditation, and posture-based yoga increased overall brain wave activity. Increases in graygray matter along with increases in amygdala and frontal cortex activation were evident after a yoga intervention. Yoga practice may be an effective adjunctive treatment for a clinical and healthy aging population. Further research can examine the effects of specific branches of yoga on a designated clinical population. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators].

PubMed

Zaĭtseva, Iu V; Granik, V G; Belik, A S; Koksharova, O A; Khmel', I A

2010-01-01

Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation.

Neurotransmitters couple brain activity to subventricular zone neurogenesis

PubMed Central

Young, Stephanie Z.; Taylor, M. Morgan; Bordey, Angélique

2011-01-01

Adult neurogenesis occurs in two privileged microenvironments, the hippocampal subgranular zone of the dentate gyrus and the subventricular zone (SVZ) along the lateral ventricle. This review focuses on accumulating evidence suggesting that the activity of specific brain regions or bodily states influences SVZ cell proliferation and neurogenesis. Neuromodulators such as dopamine and serotonin have been shown to have long-range effects through neuronal projections into the SVZ. Local GABA and glutamate signaling have demonstrated effects on SVZ proliferation and neurogenesis, but an extra-niche source of these neurotransmitters remains to be explored and options will be discussed. There is also accumulating evidence that diseases and bodily states such as Alzheimer's disease, seizures, sleep, and pregnancy influence SVZ cell proliferation. With such complex behavior and environmentally-driven factors that control subregion-specific activity, it will become necessary to account for overlapping roles of multiple neurotransmitter systems on neurogenesis when developing cell therapies or drug treatments. PMID:21395856

Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

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

Yu, S.-H.; Wang, T.-H.; Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11227, Taiwan

2009-01-09

Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU {yields} GUU) at the GU dinucleotide while left the wild-type (WT)more » K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.« less

Targeting Inhibition of Fibroblast Activation Protein-α and Prolyl Oligopeptidase Activities on Cells Common to Metastatic Tumor Microenvironments1

PubMed Central

Christiansen, Victoria J; Jackson, Kenneth W; Lee, Kyung N; Downs, Tamyra D; McKee, Patrick A

2013-01-01

Fibroblast activation protein (FAP), a membrane prolyl-specific proteinase with both dipeptidase and endopeptidase activities, is overexpressed by reactive stromal fibroblasts during epithelial-derived cancer growth. FAP digests extracellular matrix as tissue is remodeled during cancer expansion and may also promote an immunotolerant tumor microenvironment. Recent studies suggest that nonspecific FAP inhibitors suppress human cancer xenografts in mouse models. Prolyl oligopeptidase (POP), another prolyl-specific serine proteinase, is also elevated in many cancers and may have a regulatory role in angiogenesis promotion. FAP and POP cell-associated activities may be targets for diagnosis and treatment of various cancers, but their accessibilities to highly effective specific inhibitors have not been shown for cells important to cancer growth. Despite their frequent simultaneous expression in many cancers and their overlapping activities toward commonly used substrates, precise, separate measurement of FAP or POP activity has largely been ignored. To distinguish each of the two activities, we synthesized highly specific substrates and inhibitors for FAP or POP based on amino acid sequences surrounding the scissile bonds of their respective putative substrates. We found varying amounts of FAP and POP protein and activities on activated fibroblasts, mesenchymal cells, normal breast cells, and one breast cancer cell line, with some cells exhibiting more POP than FAP activity. Replicating endothelial cells (ECs) expressed POP but not FAP until tubulogenesis began. Targeting FAP-positive cells, especially mesenchymal stem cells and cancer-associated fibroblasts for inactivation or destruction, and inhibiting POP-producing EC may abrogate stromal invasion and angiogenesis simultaneously and thereby diminish cancer growth. PMID:23555181

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

PubMed

von Hundelshausen, Philipp; Agten, Stijn M; Eckardt, Veit; Blanchet, Xavier; Schmitt, Martin M; Ippel, Hans; Neideck, Carlos; Bidzhekov, Kiril; Leberzammer, Julian; Wichapong, Kanin; Faussner, Alexander; Drechsler, Maik; Grommes, Jochen; van Geffen, Johanna P; Li, He; Ortega-Gomez, Almudena; Megens, Remco T A; Naumann, Ronald; Dijkgraaf, Ingrid; Nicolaes, Gerry A F; Döring, Yvonne; Soehnlein, Oliver; Lutgens, Esther; Heemskerk, Johan W M; Koenen, Rory R; Mayo, Kevin H; Hackeng, Tilman M; Weber, Christian

2017-04-05

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting. Copyright © 2017, American Association for the Advancement of Science.

Neck-specific training with a cognitive behavioural approach compared with prescribed physical activity in patients with cervical radiculopathy: a protocol of a prospective randomised clinical trial.

PubMed

Dedering, Åsa; Halvorsen, Marie; Cleland, Joshua; Svensson, Mikael; Peolsson, Anneli

2014-08-12

Patients with cervical radiculopathy often have neck- and arm pain, neurological changes, activity limitations and difficulties in returning to work. Most patients are not candidates for surgery but are often treated with different conservative approaches and may be sick-listed for long periods. The purpose of the current study is to compare the effectiveness of neck-specific training versus prescribed physical activity. The current protocol is a two armed intervention randomised clinical trial comparing the outcomes of patients receiving neck specific training or prescribed physical activity. A total of 144 patients with cervical radiculopathy will be randomly allocated to either of the two interventions. The interventions will be delivered by experienced physiotherapists and last 14 weeks. The primary outcome variable is neck- and arm pain intensity measured with a Visual Analogue Scale accompanied with secondary outcome measures of impairments and subjective health measurements collected before intervention and at 3, 6, 12 and 24 months after base-line assessment. We anticipate that the results of this study will provide evidence to support recommendations as to the effectiveness of conservative interventions for patients with cervical radiculopathy. ClinicalTrials.gov identifier: NCT01831271.

Face adaptation aftereffects reveal anterior medial temporal cortex role in high level category representation.

PubMed

Furl, N; van Rijsbergen, N J; Treves, A; Dolan, R J

2007-08-01

Previous studies have shown reductions of the functional magnetic resonance imaging (fMRI) signal in response to repetition of specific visual stimuli. We examined how adaptation affects the neural responses associated with categorization behavior, using face adaptation aftereffects. Adaptation to a given facial category biases categorization towards non-adapted facial categories in response to presentation of ambiguous morphs. We explored a hypothesis, posed by recent psychophysical studies, that these adaptation-induced categorizations are mediated by activity in relatively advanced stages within the occipitotemporal visual processing stream. Replicating these studies, we find that adaptation to a facial expression heightens perception of non-adapted expressions. Using comparable behavioral methods, we also show that adaptation to a specific identity heightens perception of a second identity in morph faces. We show both expression and identity effects to be associated with heightened anterior medial temporal lobe activity, specifically when perceiving the non-adapted category. These regions, incorporating bilateral anterior ventral rhinal cortices, perirhinal cortex and left anterior hippocampus are regions previously implicated in high-level visual perception. These categorization effects were not evident in fusiform or occipital gyri, although activity in these regions was reduced to repeated faces. The findings suggest that adaptation-induced perception is mediated by activity in regions downstream to those showing reductions due to stimulus repetition.

Promoting Technology-Assisted Active Learning in Computer Science Education

ERIC Educational Resources Information Center

Gao, Jinzhu; Hargis, Jace

2010-01-01

This paper describes specific active learning strategies for teaching computer science, integrating both instructional technologies and non-technology-based strategies shown to be effective in the literature. The theoretical learning components addressed include an intentional method to help students build metacognitive abilities, as well as…

Using Challenge Course Activities to Teach Organizational Ethics

ERIC Educational Resources Information Center

Goltz, Sonia M.; Hietapelto, Amy B.

2006-01-01

Few learning experiences give students immediate feedback on ethical and unethical behaviors and provide opportunities to repeatedly practice effective behaviors. This article describes how the authors have used challenge course activities to stimulate students to observe their own and others' ethical and unethical behaviors. Specifically, these…

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

PubMed

Polstein, Lauren R; Perez-Pinera, Pablo; Kocak, D Dewran; Vockley, Christopher M; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

2015-08-01

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. © 2015 Polstein et al.; Published by Cold Spring Harbor Laboratory Press.

Re-examination of the Pt Particle Size Effect on the Oxygen Reduction Reaction for Ultrathin Uniform Pt/C Catalyst Layers without Influence from Nafion

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

Shinozaki, Kazuma; Morimoto, Yu; Pivovar, Bryan S.

The platinum 'particle size effect' on the oxygen reduction reaction (ORR) has been re-evaluated using commercial Pt/C catalysts (2-10 nm Pt particle) and polycrystalline Pt (poly-Pt) in 0.1 M HClO4 with a rotating disk electrode method. Nafion-free catalyst layers were employed to obtain specific activities (SA) that were not perturbed (suppressed) by sulfonate anion adsorption/blocking. By using ultrathin uniform catalyst layers, O2 diffusion limitation was minimized as confirmed from the high SAs of our supported catalysts that were comparable to unsupported sputtered Pt having controlled sizes. The specific activity (SA) steeply increased for the particle sizes in the range -2-10more » nm (0.8-1.8 mA/cm2Pt at 0.9 V vs. RHE) and plateaued over -10 nm to 2.7 mA/cm2Pt for bulk poly-Pt. On the basis of the activity trend for the range of particle sizes studied, it appears that the effect of carbon support on activity is negligible. The experimental results and the concomitant profile of SA vs. particle size was found to be in an agreement to a truncated octahedral particle model that assumes active terrace sites.« less

Nootropic Effects of Filipendula Vulgaris Moench Water Extract Fractions.

PubMed

Shilova, I V; Suslov, N I; Amelchenko, V P

2015-07-01

Nootropic activity of water extract fractions from aerial parts of Filipendula vulgaris Moench was demonstrated on the models of hermetic volume hypoxia, conditioned passive avoidance response, open field test, and forced swimming with a load. The fractions stimulated hypoxic resistance, normalized orientation and exploratory behavior, improved conditioned response reproduction during testing after hypoxic injury, and increased exercise tolerance. Fractionation of the extract led to dissociation of the effect components, which suggests that individual constituents have specific characteristics. Ethylacetate fraction exhibited most pronounced nootropic activity and was superior to plant extract by some characteristics. The detected effects seemed to be caused by modulation of the hippocampus activity the under the effects of phenol and triterpene compounds.

Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma

PubMed Central

Don, Elena; Farafonova, Olga; Pokhil, Suzanna; Barykina, Darya; Nikiforova, Marina; Shulga, Darya; Borshcheva, Alena; Tarasov, Sergey; Ermolaeva, Tatyana; Epstein, Oleg

2016-01-01

In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs. PMID:26791304

Hyperglycaemia promotes human brain microvascular endothelial cell apoptosis via induction of protein kinase C-ßI and prooxidant enzyme NADPH oxidase.

PubMed

Shao, Beili; Bayraktutan, Ulvi

2014-01-01

Blood-brain barrier disruption represents a key feature in hyperglycaemia-aggravated cerebral damage after an ischaemic stroke. Although the underlying mechanisms remain largely unknown, activation of protein kinase C (PKC) is thought to play a critical role. This study examined whether apoptosis of human brain microvascular endothelial cells (HBMEC) might contribute to hyperglycaemia-evoked barrier damage and assessed the specific role of PKC in this phenomenon. Treatments with hyperglycaemia (25 mM) or phorbol myristate acetate (PMA, a protein kinase C activator, 100 nM) significantly increased NADPH oxidase activity, O2 (•-) generation, proapoptotic protein Bax expression, TUNEL-positive staining and caspase-3/7 activities. Pharmacological inhibition of NADPH oxidase, PKC-a, PKC-ß or PKC-ßI via their specific inhibitors and neutralisation of O2 (•-) by a cell-permeable superoxide dismutase mimetic, MnTBAP normalised all the aforementioned increases induced by hyperglycaemia. Suppression of these PKC isoforms also negated the stimulatory effects of hyperglycaemia on the protein expression of NADPH oxidase membrane-bound components, Nox2 and p22-phox which determine the overall enzymatic activity. Silencing of PKC-ßI gene through use of specific siRNAs abolished the effects of both hyperglycaemia and PMA on endothelial cell NADPH oxidase activity, O2 (•-) production and apoptosis and consequently improved the integrity and function of an in vitro model of human cerebral barrier comprising HBMEC, astrocytes and pericytes. Hyperglycaemia-mediated apoptosis of HBMEC contributes to cerebral barrier dysfunction and is modulated by sequential activations of PKC-ßI and NADPH oxidase.

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.

PubMed

Slotkin, Theodore A; Skavicus, Samantha; Stapleton, Heather M; Seidler, Frederic J

2017-09-01

In addition to their activity as endocrine disruptors, brominated and organophosphate flame retardants are suspected to be developmental neurotoxicants, although identifying their specific mechanisms for that activity has been elusive. In the current study, we evaluated the effects of several flame retardants on neurodifferentiation using two in vitro models that assess distinct "decision nodes" in neural cell development: embryonic rat neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors, and rat neuronotypic PC12 cells, which characterize a later stage where cells committed to a neuronal phenotype undergo neurite outgrowth and neurotransmitter specification. In NSCs, both brominated and organophosphate flame retardants diverted the phenotype in favor of glia and away from formation of neurons, leading to an increased glia/neuron ratio, a common hallmark of the in vivo effects of neurotoxicants. For this early decision node, the brominated flame retardants were far more potent than the organophosphates. In PC12 cells, the brominated flame retardants were far less effective, whereas tris (1,3-dichloro-2-propyl) phosphate, an organophosphate, was more effective. Thus, the two classes of flame retardants differentially impact the two distinct vulnerable periods of neurodifferentiation. Furthermore, the effects on neurodifferentiation were separable from outright cytotoxicity, an important requirement in establishing a specific effect of these agents on neural cell development. These results reinforce the likelihood that flame retardants act as developmental neurotoxicants via direct effects on neural cell differentiation, over and above other activities that can impact nervous system development, such as endocrine disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential neurobiological effects of expert advice on risky choice in adolescents and adults.

PubMed

Engelmann, Jan B; Moore, Sara; Monica Capra, C; Berns, Gregory S

2012-06-01

We investigated behavioral and neurobiological mechanisms by which risk-averse advice, provided by an expert, affected risky decisions across three developmental groups [early adolescents (12-14 years), late adolescents (15-17 years), adults (18+ years)]. Using cumulative prospect theory, we modeled choice behavior during a risky-choice task. Results indicate that advice had a significantly greater impact on risky choice in both adolescent groups than in adults. Using functional magnetic resonance imaging, we investigated the neural correlates of this behavioral effect. Developmental effects on correlations between brain activity and valuation parameters were obtained in regions that can be classified into (i) cognitive control regions, such as dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC; (ii) social cognition regions, such as posterior temporoparietal junction; and (iii) reward-related regions, such as ventromedial PFC (vmPFC) and ventral striatum. Within these regions, differential effects of advice on neural correlates of valuation were observed across development. Specifically, advice increased the correlation strength between brain activity and parameters reflective of safe choice options in adolescent DLPFC and decreased correlation strength between activity and parameters reflective of risky choice options in adult vmPFC. Taken together, results indicate that, across development, distinct brain systems involved in cognitive control and valuation mediate the risk-reducing effect of advice during decision making under risk via specific enhancements and reductions of the correlation strength between brain activity and valuation parameters.

Effectiveness of Social Marketing Interventions to Promote Physical Activity Among Adults: A Systematic Review.

PubMed

Xia, Yuan; Deshpande, Sameer; Bonates, Tiberius

2016-11-01

Social marketing managers promote desired behaviors to an audience by making them tangible in the form of environmental opportunities to enhance benefits and reduce barriers. This study proposed "benchmarks," modified from those found in the past literature, that would match important concepts of the social marketing framework and the inclusion of which would ensure behavior change effectiveness. In addition, we analyzed behavior change interventions on a "social marketing continuum" to assess whether the number of benchmarks and the role of specific benchmarks influence the effectiveness of physical activity promotion efforts. A systematic review of social marketing interventions available in academic studies published between 1997 and 2013 revealed 173 conditions in 92 interventions. Findings based on χ 2 , Mallows' Cp, and Logical Analysis of Data tests revealed that the presence of more benchmarks in interventions increased the likelihood of success in promoting physical activity. The presence of more than 3 benchmarks improved the success of the interventions; specifically, all interventions were successful when more than 7.5 benchmarks were present. Further, primary formative research, core product, actual product, augmented product, promotion, and behavioral competition all had a significant influence on the effectiveness of interventions. Social marketing is an effective approach in promoting physical activity among adults when a substantial number of benchmarks are used and when managers understand the audience, make the desired behavior tangible, and promote the desired behavior persuasively.

Local effect of compression stockings on skin microcirculatory activity through the measurement of skin effective thermal conductivity.

PubMed

Grenier, Etienne; Gehin, Claudine; Lun, Bertrand; McAdams, Eric

2013-01-01

This paper presents a preliminary study to demonstrate the instantaneous local effect of compression stocking (Class 2) on skin microcirculatory activity. The measurement needs to be carefully performed as the sensor is placed under the garment. To assess the local effect of compression stockings, we use the ambulatory device Hematron located on the calf under the garment. Skin microcirculatory activity is assessed through the skin's effective thermal conductivity measurement. A specific housing for the sensor has been designed to avoid excessive pressure induced by the sensor when squeezed by stockings. The experiment, conducted on ten healthy subjects, comprised two stages: without and with compression stockings. Skin effective thermal conductivity was recorded at three successive positions (supine, sitting and standing). Significant improvement in skin microcirculatory activity was recorded by the Hematron device for the three positions. We have also demonstrated that Hematron sensor can be used under compression stockings.

A Synthesis of Current Research On Marijuana

ERIC Educational Resources Information Center

Brubaker, Timothy H.

1973-01-01

Since the isolation of the active component of marijuana (THC), studies have revealed various effects to the memory, specific physiological effects, and definite visual effects to individuals while under the influence of marijuana. The sociological aspects of the drug may stimulate an individual into the use of this drug. (Author)

Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines.

PubMed

Salem, Mohamed Labib

2005-06-01

Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.

Responsiveness of outcome measures for upper limb prosthetic rehabilitation.

PubMed

Resnik, Linda; Borgia, Matthew

2016-02-01

There is limited research on responsiveness of prosthetic rehabilitation outcome measures. To examine responsiveness of the Box and Block test, Jebsen-Taylor Hand Function tests, Upper Extremity Functional Scale, University of New Brunswick skill and spontaneity tests, Activity Measure for Upper Limb Amputation, and the Patient-Specific Functional Scale. This was a quasi-experimental study with repeated measurements in a convenience sample of upper limb amputees. Measures were collected before, during, and after training with the DEKA Arm. Largest effect sizes were observed for Patient-Specific Functional Scale (effect size: 1.59, confidence interval: 1.00, 2.14), Activity Measure for Upper Limb Amputation (effect size: 1.33, confidence interval: 0.73, 1.90), and University of New Brunswick skill test (effect size: 1.18, confidence interval: 0.61, 1.73). Other measures that were responsive to change were Box and Block test, Jebsen-Taylor Hand Function light and heavy can tests, and University of New Brunswick spontaneity test. Responsiveness and pattern of responsiveness varied by prosthetic level. The Box and Block test, Jebsen-Taylor Hand Function light and heavy can tests, University of New Brunswick skill and spontaneity tests, Activities Measure for Upper Limb Amputation, and the Patient-Specific Functional Scale were responsive to change during prosthetic training. These findings have implications for choice of measures for research and practice and inform clinicians about the amount of training necessary to maximize outcomes with the DEKA Arm. Findings on responsiveness of outcome measures have implications for the choice of measures for clinical trials and practice. Findings regarding the responsiveness to change over the course of training can inform clinicians about the amount of training that may be necessary to maximize specific outcomes with the DEKA Arm. © The International Society for Prosthetics and Orthotics 2014.

Organ-specific SPECT activity calibration using 3D printed phantoms for molecular radiotherapy dosimetry.

PubMed

Robinson, Andrew P; Tipping, Jill; Cullen, David M; Hamilton, David; Brown, Richard; Flynn, Alex; Oldfield, Christopher; Page, Emma; Price, Emlyn; Smith, Andrew; Snee, Richard

2016-12-01

Patient-specific absorbed dose calculations for molecular radiotherapy require accurate activity quantification. This is commonly derived from Single-Photon Emission Computed Tomography (SPECT) imaging using a calibration factor relating detected counts to known activity in a phantom insert. A series of phantom inserts, based on the mathematical models underlying many clinical dosimetry calculations, have been produced using 3D printing techniques. SPECT/CT data for the phantom inserts has been used to calculate new organ-specific calibration factors for (99m) Tc and (177)Lu. The measured calibration factors are compared to predicted values from calculations using a Gaussian kernel. Measured SPECT calibration factors for 3D printed organs display a clear dependence on organ shape for (99m) Tc and (177)Lu. The observed variation in calibration factor is reproduced using Gaussian kernel-based calculation over two orders of magnitude change in insert volume for (99m) Tc and (177)Lu. These new organ-specific calibration factors show a 24, 11 and 8 % reduction in absorbed dose for the liver, spleen and kidneys, respectively. Non-spherical calibration factors from 3D printed phantom inserts can significantly improve the accuracy of whole organ activity quantification for molecular radiotherapy, providing a crucial step towards individualised activity quantification and patient-specific dosimetry. 3D printed inserts are found to provide a cost effective and efficient way for clinical centres to access more realistic phantom data.

Peripheral Blood Signatures of Lead Exposure

PubMed Central

LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

2011-01-01

Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

Neuropeptidergic Signaling Partitions Arousal Behaviors in Zebrafish

PubMed Central

Schoppik, David; Shi, Veronica J.; Zimmerman, Steven; Coleman, Haley A.; Greenwood, Joel; Soucy, Edward R.

2014-01-01

Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal. PMID:24573274

Determinants of information technology outsourcing among health maintenance organizations.

PubMed

Wholey, D R; Padman, R; Hamer, R; Schwartz, S

2001-09-01

We analyze the determinants of HMO information technology outsourcing using two studies. Study 1 examines the effect of asset specificity on outsourcing for development and operation activities, using HMO specific fixed effects to control for differences between HMOs. Study 2 regresses the HMO specific fixed effects from Study 1, which measure an HMO's propensity to outsource, on HMO characteristics. The data comes from a 1995 InterStudy survey about information technology organization of HMOs. While HMOs split roughly equally in outsourcing information technology development activities, they are extremely unlikely to outsource the day-to-day operation of information systems. The greater an HMO's information technology capability and the complexity of information systems supported, the less likely is an HMO to outsource. While HMOs less than two years old, for-profit HMOs, local or Blue Cross-affiliated HMOs, and mixed HMOs are more likely to outsource, federally qualified HMOs are less likely to outsource. Policy and managerial implications for the adoption and diffusion of new ways of organizing information technology, such as application service providers (ASPs), are discussed.

Effects of category-specific costs on neural systems for perceptual decision-making.

PubMed

Fleming, Stephen M; Whiteley, Louise; Hulme, Oliver J; Sahani, Maneesh; Dolan, Raymond J

2010-06-01

Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category-specific cost in keeping with the hypothesis that loss functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between perception and action, expressed via general effects on frontal cortex, and selective effects on extrastriate cortex. These findings indicate that asymmetric costs may affect a neural implementation of perceptual decision making in a similar manner to changes in category expectation, constituting a step toward accounting for how prospective losses are flexibly integrated with sensory evidence in the brain.

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

PubMed Central

Zambirinis, Constantinos P.; Levie, Elliot; Nguy, Susanna; Avanzi, Antonina; Barilla, Rocky; Xu, Yijie; Seifert, Lena; Daley, Donnele; Greco, Stephanie H.; Deutsch, Michael; Jonnadula, Saikiran; Torres-Hernandez, Alejandro; Tippens, Daniel; Pushalkar, Smruti; Eisenthal, Andrew; Saxena, Deepak; Ahn, Jiyoung; Hajdu, Cristina; Engle, Dannielle D.; Tuveson, David

2015-01-01

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis. PMID:26481685

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.

PubMed

Zambirinis, Constantinos P; Levie, Elliot; Nguy, Susanna; Avanzi, Antonina; Barilla, Rocky; Xu, Yijie; Seifert, Lena; Daley, Donnele; Greco, Stephanie H; Deutsch, Michael; Jonnadula, Saikiran; Torres-Hernandez, Alejandro; Tippens, Daniel; Pushalkar, Smruti; Eisenthal, Andrew; Saxena, Deepak; Ahn, Jiyoung; Hajdu, Cristina; Engle, Dannielle D; Tuveson, David; Miller, George

2015-11-16

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis. © 2015 Zambirinis et al.

Mu Opioid Mediated Discriminative-Stimulus Effects of Tramadol: An Individual Subjects Analysis

PubMed Central

Strickland, Justin C.; Rush, Craig R.; Stoops, William W.

2015-01-01

Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human subjects. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human subjects first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to subjects after acquiring the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all subjects. These effects were attenuated by naltrexone. Individual subject records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure. PMID:25664525

A training paradigm to enhance motor recovery in contused rats: effects of staircase training.

PubMed

Singh, Anita; Murray, Marion; Houle, John D

2011-01-01

Ambulating on stairs is an important aspect of daily activities for many individuals with incomplete spinal cord injury (SCI), and little is known about the effect of training for this specific task. The goal of this study was to determine whether staircase ascent training enhances motor recovery in animals with contusion injury. Rats received a midthoracic contusion lesion of moderate severity and were randomly divided into 2 groups, with one group receiving staircase ascent training for up to 8 weeks and the other receiving no training. To assess the direct effect of training, a task-specific staircase climbing test was performed. Open field test (BBB) and gait analysis (CatWalk) assessed overground recovery, and a grid test was used to assess improvement in sensorimotor tasks. Changes in muscle mass of the forelimb and hindlimb muscles were also measured, and the extent of spared white matter was determined for lesion verification and anatomical correlations. Staircase training improved the task-specific performance of ascent. Gait parameters, including base of support, stride length, regularity index (RI), and step sequence, also improved. Overground locomotion and the grid test, both showed a trend of improved performance. Finally, hindlimb muscle mass was maintained with training. Staircase ascent training after incomplete SCI has beneficial effects on task-specific as well as nonspecific motor and sensorimotor activities.

Preparatory neural activity predicts performance on a conflict task.

PubMed

Stern, Emily R; Wager, Tor D; Egner, Tobias; Hirsch, Joy; Mangels, Jennifer A

2007-10-24

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

Meta-analysis of functional brain imaging in specific phobia.

PubMed

Ipser, Jonathan C; Singh, Leesha; Stein, Dan J

2013-07-01

Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation

PubMed Central

Wang, Juan; Huang, Liying; Li, Jian; Fan, Qiangwang; Long, Yicheng; Li, Ying; Zhou, Bing

2010-01-01

The biological mode of action of artemisinin, a potent antimalarial, has long been controversial. Previously we established a yeast model addressing its mechanism of action and found mitochondria the key in executing artemisinin's action. Here we present data showing that artemisinin directly acts on mitochondria and it inhibits malaria in a similar way as yeast. Specifically, artemisinin and its homologues exhibit correlated activities against malaria and yeast, with the peroxide bridge playing a key role for their inhibitory action in both organisms. In addition, we showed that artemisinins are distributed to malarial mitochondria and directly impair their functions when isolated mitochondria were tested. In efforts to explore how the action specificity of artemisinin is achieved, we found strikingly rapid and dramatic reactive oxygen species (ROS) production is induced with artemisinin in isolated yeast and malarial but not mammalian mitochondria, and ROS scavengers can ameliorate the effects of artemisinin. Deoxyartemisinin, which lacks an endoperoxide bridge, has no effect on membrane potential or ROS production in malarial mitochondria. OZ209, a distantly related antimalarial endoperoxide, also causes ROS production and depolarization in isolated malarial mitochondria. Finally, interference of mitochondrial electron transport chain (ETC) can alter the sensitivity of the parasite towards artemisinin. Addition of iron chelator desferrioxamine drastically reduces ETC activity as well as mitigates artemisinin-induced ROS production. Taken together, our results indicate that mitochondrion is an important direct target, if not the sole one, in the antimalarial action of artemisinins. We suggest that fundamental differences among mitochondria from different species delineate the action specificity of this class of drugs, and differing from many other drugs, the action specificity of artemisinins originates from their activation mechanism. PMID:20221395

Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C 82(OH) 22 and its implication for de novo design of nanomedicine

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

Kang, S. -g.; Zhou, G.; Yang, P.

2012-09-18

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C 82(OH) 22 can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C 82(OH) 22 effectively blocks tumor growth in human pancreatic cancermore » xenografts in a nude mouse model. Enzyme activity assays also show Gd@C 82(OH) 22 not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C 82(OH) 22–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C 82(OH) 22 inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C 82(OH) 22 exhibits specific binding modes near the ligand-specificity loop S1', thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C 82(OH) 22 a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Finally, our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.« less

Which behaviour change techniques are most effective at increasing older adults' self-efficacy and physical activity behaviour? A systematic review.

PubMed

French, David P; Olander, Ellinor K; Chisholm, Anna; Mc Sharry, Jennifer

2014-10-01

Increasing self-efficacy is an effective mechanism for increasing physical activity, especially for older people. The aim of this review was to identify behaviour change techniques (BCTs) that increase self-efficacy and physical activity behaviour in non-clinical community-dwelling adults 60 years or over. A systematic search identified 24 eligible studies reporting change in self-efficacy for physical activity following an intervention. Moderator analyses examined whether the inclusion of specific BCTs (as defined by CALO-RE taxonomy) was associated with changes in self-efficacy and physical activity behaviour. Overall, interventions increased self-efficacy (d = 0.37) and physical activity (d = 0.14). Self-regulatory techniques such as setting behavioural goals, prompting self-monitoring of behaviour, planning for relapses, providing normative information and providing feedback on performance were associated with lower levels of both self-efficacy and physical activity. Many commonly used self-regulation intervention techniques that are effective for younger adults may not be effective for older adults.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity.

PubMed

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo; Lee, Daeho

2011-04-01

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Extracurricular Activities and the Development of Social Skills in Children with Intellectual and Specific Learning Disabilities

ERIC Educational Resources Information Center

Brooks, B. A.; Floyd, F.; Robins, D. L.; Chan, W. Y.

2015-01-01

Background: Children with intellectual disability and specific learning disabilities often lack age-appropriate social skills, which disrupts their social functioning. Because of the limited effectiveness of classroom mainstreaming and social skills training for these children, it is important to explore alternative opportunities for social skill…

Using Web-based Tutorials To Enhance Library Instruction.

ERIC Educational Resources Information Center

Kocour, Bruce G.

2000-01-01

Describes the development of a Web site for library instruction at Carson-Newman College (TN) and its integration into English composition courses. Describes the use of a virtual tour, a tutorial on database searching, tutorials on specific databases, and library guides to specific disciplines to create an effective mechanism for active learning.…

Immunotoxicological Analysis of the Immune Adjuvant Effects of Source Specific Diesel and Environmental Ambient Particulate Matter in a Murine Sensitization And Challenge Model.

EPA Science Inventory

Rationale: Acute exposure to ambient particulate matter (APM) provokes oxidative and inflammatory lung activation in vivo. Here, we test the hypothesis that environmental diesel exhaust particles (eDEP), emission source-specific DEP (cDEP) and APM differentially provoke an allerg...

Effect of heavy metals on nitrification activity as measured by RNA- and DNA-based function-specific assays

EPA Science Inventory

Heavy metals can inhibit nitrification, a key process for nitrogen removal in wastewater treatment. The transcriptional responses of functional genes (amoA, hao, nirK and norB) were measured in conjunction with specific oxygen uptake rate (sOUR) for nitrifying enrichment cultures...

The Adjuvant Effects of High-Molecule-Weight Polysaccharides Purified from Antrodia cinnamomea on Dendritic Cell Function and DNA Vaccines

PubMed Central

Lin, Chi-Chen; Pan, I-Hong; Li, Yi-Rong; Pan, Yi-Gen; Lin, Ming-Kuem; Lu, Yi-Huang; Wu, Hsin-Chieh; Chu, Ching-Liang

2015-01-01

The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants. PMID:25723174

Regulation of Alternative Splicing in Vivo by Overexpression of Antagonistic Splicing Factors

NASA Astrophysics Data System (ADS)

Caceres, Javier F.; Stamm, Stefan; Helfman, David M.; Krainer, Adrian R.

1994-09-01

The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or hnRNP A1 complementary DNAs were transiently overexpressed in HeLa cells, and the effect on alternative splicing of several cotransfected reporter genes was measured. Increased expression of SF2/ASF activated proximal 5' splice sites, promoted inclusion of a neuron-specific exon, and prevented abnormal exon skipping. Increased expression of hnRNP A1 activated distal 5' splice sites. Therefore, variations in the intracellular levels of antagonistic splicing factors influence different modes of alternative splicing in vivo and may be a natural mechanism for tissue-specific or developmental regulation of gene expression.

Activity measurement and effective dose modelling of natural radionuclides in building material.

PubMed

Maringer, F J; Baumgartner, A; Rechberger, F; Seidel, C; Stietka, M

2013-11-01

In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown. Copyright © 2013 Elsevier Ltd. All rights reserved.

The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase

PubMed Central

Cross, Janet V; Foss, Frank W; Rady, Joshua M; Macdonald, Timothy L; Templeton, Dennis J

2007-01-01

Background Dietary isothiocyanates (ITCs) are electrophilic compounds that have diverse biological activities including induction of apoptosis and effects on cell cycle. They protect against experimental carcinogenesis in animals, an activity believed to result from the transcriptional induction of "Phase 2" enzymes. The molecular mechanism of action of ITCs is unknown. Since ITCs are electrophiles capable of reacting with sulfhydryl groups on amino acids, we hypothesized that ITCs induce their biological effects through covalent modification of proteins, leading to changes in cell regulatory events. We previously demonstrated that stress-signaling kinase pathways are inhibited by other electrophilic compounds such as menadione. We therefore tested the effects of nutritional ITCs on MEKK1, an upstream regulator of the SAPK/JNK signal transduction pathway. Methods The activity of MEKK1 expressed in cells was monitored using in vitro kinase assays to measure changes in catalytic activity. The activity of endogenous MEKK1, immunopurified from ITC treated and untreated LnCAP cells was also measured by in vitro kinase assay. A novel labeling and affinity reagent for detection of protein modification by ITCs was synthesized and used in competition assays to monitor direct modification of MEKK1 by ITC. Finally, immunoblots with phospho-specific antibodies were used to measure the activity of MAPK protein kinases. Results ITCs inhibited the MEKK1 protein kinase in a manner dependent on a specific cysteine residue in the ATP binding pocket. Inhibition of MEKK1 catalytic activity was due to direct, covalent and irreversible modification of the MEKK1 protein itself. In addition, ITCs inhibited the catalytic activity of endogenous MEKK1. This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase. This inhibition was specific to SAPK, as parallel MAPK pathways were unaffected. Conclusion These results demonstrate that MEKK1 is directly modified and inhibited by ITCs, and that this correlates with inhibition of downstream activation of SAPK. These results support the conclusion that ITCs may carry out many of their actions by directly targeting important cell regulatory proteins. PMID:17894894

Activation of structural carbon fibres for potential applications in multifunctional structural supercapacitors.

PubMed

Qian, Hui; Diao, Hele; Shirshova, Natasha; Greenhalgh, Emile S; Steinke, Joachim G H; Shaffer, Milo S P; Bismarck, Alexander

2013-04-01

The feasibility of modifying conventional structural carbon fibres via activation has been studied to create fibres, which can be used simultaneously as electrode and reinforcement in structural composite supercapacitors. Both physical and chemical activation, including using steam, carbon dioxide, acid and potassium hydroxide, were conducted and the resulting fibre properties compared. It was proven that the chemical activation using potassium hydroxide is an effective method to prepare activated structural carbon fibres that possess both good electrochemical and mechanical properties. The optimal activation conditions, such as the loading of activating agent and the burn-off of carbon fibres, was identified and delivered a 100-fold increase in specific surface area and 50-fold improvement in specific electrochemical capacitance without any degradation of the fibre mechanical properties. The activation process was successfully scaled-up, showing good uniformity and reproducibility. These activated structural carbon fibres are promising candidates as reinforcement/electrodes for multifunctional structural energy storage devices. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural Correlates of Expert Behavior During a Domain-Specific Attentional Cueing Task in Badminton Players.

PubMed

Wang, Chun-Hao; Tu, Kuo-Cheng

2017-06-01

The present study aimed to investigate the neural correlates associated with sports expertise during a domain-specific task in badminton players. We compared event-related potentials activity from collegiate male badminton players and a set of matched athletic controls when they performed a badminton-specific attentional cueing task in which the uncertainty and validity were manipulated. The data showed that, regardless of cue type, the badminton players had faster responses along with greater P3 amplitudes than the athletic controls on the task. Specifically, the contingent negative variation amplitude was smaller for the players than for the controls in the condition involving higher uncertainty. Such an effect, however, was absent in the condition with lower uncertainty. We conclude that expertise in sports is associated with proficient modulation of brain activity during cognitive and motor preparation, as well as response execution, when performing a task related to an individual's specific sport domain.

Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

PubMed

Imbernon, Monica; Beiroa, Daniel; Vázquez, María J; Morgan, Donald A; Veyrat-Durebex, Christelle; Porteiro, Begoña; Díaz-Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A; Al-Massadi, Omar; Varela, Luis; Gándara, Marina; López-Soriano, Francisco-Javier; Gallego, Rosalía; Seoane, Luisa M; Argiles, Josep M; López, Miguel; Davis, Roger J; Sabio, Guadalupe; Rohner-Jeanrenaud, Françoise; Rahmouni, Kamal; Dieguez, Carlos; Nogueiras, Ruben

2013-03-01

Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism. Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot. We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism. Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems for targeted drug delivery in pancreatic cancer.

PubMed

Grünwald, Barbara; Vandooren, Jennifer; Locatelli, Erica; Fiten, Pierre; Opdenakker, Ghislain; Proost, Paul; Krüger, Achim; Lellouche, Jean Paul; Israel, Liron Limor; Shenkman, Louis; Comes Franchini, Mauro

2016-10-10

Specific cancer cell targeting is a pre-requisite for efficient drug delivery as well as for high-resolution imaging and still represents a major technical challenge. Tumor-associated enzyme-assisted targeting is a new concept that takes advantage of the presence of a specific activity in the tumor entity. MMP-9 is a protease found to be upregulated in virtually all malignant tumors. Consequently, we hypothesized that its presence can provide a de-shielding activity for targeted delivery of drugs by nanoparticles (NPs) in pancreatic cancer. Here, we describe synthesis and characterization of an optimized MMP-9-cleavable linker mediating specific removal of a PEG shield from a PLGA-b-PEG-based polymeric nanocarrier (Magh@PNPs-PEG-RegaCP-PEG) leading to specific uptake of the smaller PNPs with their cargo into cells. The specific MMP-9-cleavable linker was designed based on the degradation efficiency of peptides derived from the collagen type II sequence. MMP-9-dependent uptake of the Magh@PNPs-PEG-RegaCP-PEG was demonstrated in pancreatic cancer cells in vitro. Accumulation of the Magh@PNPs-PEG-RegaCP-PEG in pancreatic tissues in the clinically relevant KPC mouse model of pancreatic cancer, as a proof-of-concept, was tumor-specific and MMP-9-dependent, indicating that MMP-9 has a strong potential as a specific mediator of PNP de-shielding for tumor-specific uptake. Pre-treatment of mice with Magh@PNPs-PEG-RegaCP-PEG led to reduction of liver metastasis and drastically decreased average colony size. In conclusion, the increased tumor-specific presence and activity of MMP-9 can be exploited to deliver an MMP-9-activatable NP to pancreatic tumors specifically, effectively, and safely. Copyright © 2016 Elsevier B.V. All rights reserved.

Cross-reactive influenza virus–specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus–associated infectious mononucleosis

PubMed Central

Clute, Shalyn C.; Watkin, Levi B.; Cornberg, Markus; Naumov, Yuri N.; Sullivan, John L.; Luzuriaga, Katherine; Welsh, Raymond M.; Selin, Liisa K.

2005-01-01

The marked proliferation of activated CD8+ T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8+ T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8+ T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2+ IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M158–66–specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1280–288, which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM. PMID:16308574

Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis.

PubMed

Clute, Shalyn C; Watkin, Levi B; Cornberg, Markus; Naumov, Yuri N; Sullivan, John L; Luzuriaga, Katherine; Welsh, Raymond M; Selin, Liisa K

2005-12-01

The marked proliferation of activated CD8+ T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8+ T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8+ T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2+ IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M1(58-66)-specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1(280-288), which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM.

Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.

PubMed

Argaiz, Eduardo R; Chavez-Canales, Maria; Ostrosky-Frid, Mauricio; Rodriguez-Gama, Alejandro; Vázquez, Norma; Gonzalez-Rodriguez, Xochiquetzal; Garcia-Valdés, Jesus; Hadchouel, Juliette; Ellison, David H; Gamba, Gerardo

2018-05-30

Familial Hyperkalemic Hypertension (FHHt) can be mainly attributed to increased activity of the renal Na+:Cl- cotransporter (NCC), which is caused by altered expression and regulation of the WNK1 and WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/SPAK/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl-]i) is reduced or when KS-WNK1 is co-expressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl-]i. Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl-]i.

Active Learning Improves Student Performance in a Respiratory Physiology Lab

ERIC Educational Resources Information Center

Wolf, Alex M.; Liachovitzky, Carlos; Abdullahi, Abass S.

2015-01-01

This study assessed the effectiveness of the introduction of active learning exercises into the anatomy and physiology curriculum in a community college setting. Specifically, the incorporation of a spirometry-based respiratory physiology lab resulted in improved student performance in two concepts (respiratory volumes and the hallmarks of…

Emergy Evaluations of the Global Biogeochemical Cycles of Six Biologically Active Elements and Two Compounds

EPA Science Inventory

Estimates of the emergy carried by the flows of biologically active elements (BAE) and compounds are needed to accurately evaluate the near and far field effects of anthropogenic wastes. The transformities and specific emergies of these elements and of their different chemical sp...

Influence of lorcainide on microsomal Na+, K(+)-ATPase in guinea-pig isolated heart preparations.

PubMed Central

Almotrefi, A. A.; Dzimiri, N.

1991-01-01

1. The effects of lorcainide on the myocardial Mg2(+)-dependent, Na+ and K(+)-activated adenosine triphosphatase (Na+, K(+)-ATPase) were compared in guinea-pig heart preparations with those of ouabain, a specific inhibitor of the enzyme activity. 2. Both ouabain and lorcainide inhibited the microsomal Na+, K(+)-ATPase activity in a concentration-dependent fashion. Their inhibitory effective ranges were 0.05-100 microM and 0.15-125 microM, respectively, and the concentrations for half maximal inhibition (IC50 values) were 2.1 +/- 0.3 and 33.5 +/- 7.3 microM, respectively. 3. In a second series of experiments, the combined effects of the two drugs on the enzyme activity were studied. In these experiments, lorcainide produced a concentration-dependent potentiation of the inhibitory effects of ouabain on Na+, K(+)-ATPase activity. 4. The present study demonstrates that lorcainide is a potent inhibitor of myocardial Na+, K(+)-ATPase. PMID:1849773

Staphylococcal enterotoxin A-activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation.

PubMed

Zeng, Wei-Ping; McFarland, Margaret M; Zhou, Baohua; Holtfreter, Silva; Flesher, Susan; Cheung, Ambrose; Mallick, Avishek

2017-02-01

T H 2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote T H 2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a T H 2-polarizing cytokine milieu. Ovalbumin (OVA)-specific, staphylococcal enterotoxin A (SEA)-nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-specific CD4 T cells were then analyzed for IL-13 and IFN-γ expression. SEA-activated Treg cells were analyzed for the expression of the T H 2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and T H 2 differentiation in these mice were analyzed. SEA-activated Treg cells induced IL-13 but suppressed IFN-γ expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells. SEA promoted T H 2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Integrating genomics and proteomics data to predict drug effects using binary linear programming.

PubMed

Ji, Zhiwei; Su, Jing; Liu, Chenglin; Wang, Hongyan; Huang, Deshuang; Zhou, Xiaobo

2014-01-01

The Library of Integrated Network-Based Cellular Signatures (LINCS) project aims to create a network-based understanding of biology by cataloging changes in gene expression and signal transduction that occur when cells are exposed to a variety of perturbations. It is helpful for understanding cell pathways and facilitating drug discovery. Here, we developed a novel approach to infer cell-specific pathways and identify a compound's effects using gene expression and phosphoproteomics data under treatments with different compounds. Gene expression data were employed to infer potential targets of compounds and create a generic pathway map. Binary linear programming (BLP) was then developed to optimize the generic pathway topology based on the mid-stage signaling response of phosphorylation. To demonstrate effectiveness of this approach, we built a generic pathway map for the MCF7 breast cancer cell line and inferred the cell-specific pathways by BLP. The first group of 11 compounds was utilized to optimize the generic pathways, and then 4 compounds were used to identify effects based on the inferred cell-specific pathways. Cross-validation indicated that the cell-specific pathways reliably predicted a compound's effects. Finally, we applied BLP to re-optimize the cell-specific pathways to predict the effects of 4 compounds (trichostatin A, MS-275, staurosporine, and digoxigenin) according to compound-induced topological alterations. Trichostatin A and MS-275 (both HDAC inhibitors) inhibited the downstream pathway of HDAC1 and caused cell growth arrest via activation of p53 and p21; the effects of digoxigenin were totally opposite. Staurosporine blocked the cell cycle via p53 and p21, but also promoted cell growth via activated HDAC1 and its downstream pathway. Our approach was also applied to the PC3 prostate cancer cell line, and the cross-validation analysis showed very good accuracy in predicting effects of 4 compounds. In summary, our computational model can be used to elucidate potential mechanisms of a compound's efficacy.

Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways.

PubMed

Saleh, A M; Vijayasarathy, C; Masoud, L; Kumar, L; Shahin, A; Kambal, A

2003-07-01

The toxicity of organophosphorus compounds, such as paraoxon (POX), is due to their anticholinesterase action. Recently, we have shown that, at noncholinergic doses (1 to 10 nM), POX (the bioactive metabolite of parathion) causes apoptotic cell death in murine EL4 T-lymphocytic leukemia cell line through activation of caspase-3. In this study, by employing caspase-specific inhibitors, we extend our observations to elucidate the sequence of events involved in POX-stimulated apoptosis. Pretreatment of EL4 cells with the caspase-9-specific inhibitor zLEHD-fmk attenuated POX-induced apoptosis in a dose-dependent manner, whereas the caspase-8 inhibitor zIETD-fmk had no effect. Furthermore, the activation of caspase-9, -8, and -3 in response to POX treatment was completely inhibited in the presence of zLEHD-fmk, implicating the involvement of caspase 9-dependent mitochondrial pathways in POX-stimulated apoptosis. Indeed, under both in vitro and in vivo conditions, POX triggered a dose- and time-dependent translocation of cytochrome c from mitochondria into the cytosol, as assessed by Western blot analysis. Investigation of the mechanism of cytochrome c release revealed that POX disrupted mitochondrial transmembrane potential. Neither this effect nor cytchrome c release was dependent on caspase activation, since the general inhibitor of the caspase family zVAD-fmk did not influence both processes. Finally, POX treatment also resulted in a time-dependent up-regulation and translocation of the proapoptotic molecule Bax to mitochondria. Inhibition of this event by zVAD-fmk suggests that the activation and translocation of Bax to mitochondria is subsequent to activation of the caspase cascades. The results indicate that POX induces apoptosis in EL4 cells through a direct effect on mitochondria by disrupting its transmembrane potential, causing the release of cytochrome c into the cytosol and subsequent activation of caspase-9. Inhibition of this specific pathway might provide a useful strategy to minimize organophosphate-induced poisoning.

Inferring genome-wide functional modulatory network: a case study on NF-κB/RelA transcription factor.

PubMed

Li, Xueling; Zhu, Min; Brasier, Allan R; Kudlicki, Andrzej S

2015-04-01

How different pathways lead to the activation of a specific transcription factor (TF) with specific effects is not fully understood. We model context-specific transcriptional regulation as a modulatory network: triplets composed of a TF, target gene, and modulator. Modulators usually affect the activity of a specific TF at the posttranscriptional level in a target gene-specific action mode. This action may be classified as enhancement, attenuation, or inversion of either activation or inhibition. As a case study, we inferred, from a large collection of expression profiles, all potential modulations of NF-κB/RelA. The predicted modulators include many proteins previously not reported as physically binding to RelA but with relevant functions, such as RNA processing, cell cycle, mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification. Modulators from different processes exert specific prevalent action modes on distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and kinases modulate the NF-κB/RelA activity with specific action modes consistent with their molecular functions and modulation level. The modulatory networks of NF-κB/RelA in the context epithelial-mesenchymal transition (EMT) and burn injury have different modulators, including those involved in extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH, PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury.

Biasing the brain's attentional set: I. cue driven deployments of intersensory selective attention.

PubMed

Foxe, John J; Simpson, Gregory V; Ahlfors, Seppo P; Saron, Clifford D

2005-10-01

Brain activity associated with directing attention to one of two possible sensory modalities was examined using high-density mapping of human event-related potentials. The deployment of selective attention was based on visually presented symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory modality to attend. We measured the spatio-temporal pattern of activation in the approximately 1 second period between the cue-instruction and a subsequent compound auditory-visual imperative stimulus. This allowed us to assess the flow of processing across brain regions involved in deploying and sustaining inter-sensory selective attention, prior to the actual selective processing of the compound audio-visual target stimulus. Activity over frontal and parietal areas showed sensory specific increases in activation during the early part of the anticipatory period (~230 ms), probably representing the activation of fronto-parietal attentional deployment systems for top-down control of attention. In the later period preceding the arrival of the "to-be-attended" stimulus, sustained differential activity was seen over fronto-central regions and parieto-occipital regions, suggesting the maintenance of sensory-specific biased attentional states that would allow for subsequent selective processing. Although there was clear sensory biasing in this late sustained period, it was also clear that both sensory systems were being prepared during the cue-target period. These late sensory-specific biasing effects were also accompanied by sustained activations over frontal cortices that also showed both common and sensory specific activation patterns, suggesting that maintenance of the biased state includes top-down inputs from generators in frontal cortices, some of which are sensory-specific regions. These data support extensive interactions between sensory, parietal and frontal regions during processing of cue information, deployment of attention, and maintenance of the focus of attention in anticipation of impending attentionally relevant input.

Differential Role of Glutamate Dehydrogenase in Nitrogen Metabolism of Maize Tissues 1

PubMed Central

Loyola-Vargas, Victor Manuel; de Jimenez, Estela Sanchez

1984-01-01

Both calli and plantlets of maize (Zea mays L. var Tuxpeño 1) were exposed to specific nitrogen sources, and the aminative (NADH) and deaminative (NAD+) glutamate dehydrogenase activities were measured at various periods of time in homogenates of calli, roots, and leaves. A differential effect of the nitrogen sources on the tissues tested was observed. In callus tissue, glutamate, ammonium, and urea inhibited glutamate dehydrogenase (GDH) activity. The amination and deamination reactions also showed different ratios of activity under different nitrogen sources. In roots, ammonium and glutamine produced an increase in GDH-NADH activity whereas the same metabolites were inhibitory of this activity in leaves. These data suggest the presence of isoenzymes or conformers of GDH, specific for each tissue, whose activities vary depending on the nutritional requirements of the tissue and the state of differentiation. PMID:16663876

Physical activity and neuropsychiatric symptoms of Parkinson disease.

PubMed

Abrantes, Ana M; Friedman, Joseph H; Brown, Richard A; Strong, David R; Desaulniers, Julie; Ing, Eileen; Saritelli, Jennifer; Riebe, Deborah

2012-09-01

Neuropsychiatric symptoms of Parkinson disease (PD) such as fatigue, depression, and apathy are common and detract from quality of life. There is little published on the impact of physical activity on the neuropsychiatric symptoms of PD. A convenience sample of 45 patients with PD (mean age = 66.1 years; 33% female) completed questionnaires on physical activity, neuropsychiatric symptoms, and specific exercise preferences. Covarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect. Exercise preferences included moderate intensity (73%), at home (56%), in the morning (73%), scheduled (69%), options for varied activities (73%), and preference for both structured/supervised (50%), and unsupervised/self-paced (50%) programs. Preferred activities included the use of aerobic exercise equipment, resistance training, and yoga. Developing and tailoring exercise programs that incorporate specific preferences may result in more effective interventions for patients with PD.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

PubMed

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

2017-04-15

Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. Copyright © 2017 Tsai et al.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

PubMed Central

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

2017-01-01

ABSTRACT Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. PMID:28179531

Potent virucidal effect of pheophorbide a and pyropheophorbide a on enveloped viruses.

PubMed

Bouslama, Lamjed; Hayashi, Kyoko; Lee, Jung-Bum; Ghorbel, Abdelwahed; Hayashi, Toshimitsu

2011-01-01

In this study, we evaluated the inhibitory effect of ethanol and aqueous extracts from a stem of Opuntia ficus indica on replication of three kinds of viruses: two enveloped viruses [herpes simplex virus type 2 (HSV-2), influenza A virus (IFV-A)], and one non-enveloped virus [poliovirus type 1 (PV-1)]. Only ethanol extract from the cactus stem showed significant antiviral activity in vitro. Two chlorophyll derivatives, pheophorbide a and pyropheophorbide a, were isolated as active substances exhibiting potent virucidal effects on HSV-2 and IFV-A, but no activity against PV-1 was observed. These findings suggest that these active compounds might recognize specific glycoproteins of enveloped viruses, precluding their binding to host cell receptors and inhibiting viral infections.

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

PubMed

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress

PubMed Central

Wright, Matthew B.; Kucharava, Krystsina; Huerzeler, Nathan; Levano, Soledad; Brand, Yves; Leitmeyer, Katharina; Glutz, Andrea; Bausch, Alexander; Bodmer, Daniel

2017-01-01

Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants. Western blots showed high levels of PPARγ and PPARα proteins in mouse OC lysates. Immunofluorescence assays indicated that PPARγ and PPARα proteins are present in auditory HCs and other cell types in the mouse cochlea. Gentamicin treatment induced production of reactive oxygen species (ROS), lipid peroxidation, caspase activation, PARP-1 cleavage, and HC apoptosis in cultured OCs. Pioglitazone mediated its anti-apoptotic effects by opposing the increase in ROS induced by gentamicin, which inhibited the subsequent formation of 4-hydroxy-2-nonenal (4-HNE) and activation of pro-apoptotic mediators. Pioglitazone mediated its effects by upregulating genes that control ROS production and detoxification pathways leading to restoration of the reduced:oxidized glutathione ratio. Structurally diverse PPAR agonists were protective of HCs. Pioglitazone (PPARγ-specific), tesaglitazar (PPARγ/α-specific), and fenofibric acid (PPARα-specific) all provided >90% protection from gentamicin toxicity by regulation of overlapping subsets of genes controlling ROS detoxification. This study revealed that PPARs play important roles in the cochlea, and that PPAR-targeting drugs possess therapeutic potential as treatment for hearing loss. PMID:29182629

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

PubMed Central

Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

2015-01-01

Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

Effects of Astragalus polysaccharides (APS) and chitooligosaccharides (COS) on growth, immune response and disease resistance of juvenile largemouth bass, Micropterus salmoides.

PubMed

Lin, Shi-Mei; Jiang, Yu; Chen, Yong-Jun; Luo, Li; Doolgindachbaporn, Sompong; Yuangsoi, Bundit

2017-11-01

The effects of oral administration of Astragalus polysaccharides (APS) and chitooligosaccharides (COS), single or combined, on the growth performance, immunity and disease resistance of M. salmoides were investigated. Largemouth bass juvenile were divided into 4 groups and each group was fed with diets supplemented with or without immunostimulant for 8 weeks. After 8 weeks of feeding trial, five fish per tank were sampled for immunity determination, ten fish per tank were challenged by A. hydrophila. The results showed that the largemouth bass fed with two immunostimulants alone or in combination significantly enhanced the final weight and specific growth rate (SGR), decreased feed conversion ratio (FCR) (P < 0.05). However, there were no significant differences (P < 0.05) in specific growth rate (SGR) between dietary COS and dietary APS. In addition, both COS and APS upregulated respiratory burst activity (RBA), phagocytic activity (PA), lysozyme activity and superoxide dismutase (SOD) activity. Meanwhile, COS also exhibited a increase in total leukocyte count, nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity compared to the control. When challenged with A. hydrophila, the mortality of groups fed with COS and/or APS was lower than the control (P < 0.05). Under the experimental conditions, dietary APS and COS had a synergistic effect on lysozme activity, iNOS activity, NO content and disease resistance of fish (P < 0.05). Copyright © 2017 Elsevier Ltd. All rights reserved.

Engagement of the left extrastriate body area during body-part metaphor comprehension.

PubMed

Lacey, Simon; Stilla, Randall; Deshpande, Gopikrishna; Zhao, Sinan; Stephens, Careese; McCormick, Kelly; Kemmerer, David; Sathian, K

2017-03-01

Grounded cognition explanations of metaphor comprehension predict activation of sensorimotor cortices relevant to the metaphor's source domain. We tested this prediction for body-part metaphors using functional magnetic resonance imaging while participants heard sentences containing metaphorical or literal references to body parts, and comparable control sentences. Localizer scans identified body-part-specific motor, somatosensory and visual cortical regions. Both subject- and item-wise analyses showed that, relative to control sentences, metaphorical but not literal sentences evoked limb metaphor-specific activity in the left extrastriate body area (EBA), paralleling the EBA's known visual limb-selectivity. The EBA focus exhibited resting-state functional connectivity with ipsilateral semantic processing regions. In some of these regions, the strength of resting-state connectivity correlated with individual preference for verbal processing. Effective connectivity analyses showed that, during metaphor comprehension, activity in some semantic regions drove that in the EBA. These results provide converging evidence for grounding of metaphor processing in domain-specific sensorimotor cortical activity. Published by Elsevier Inc.

Time perspective and weight management behaviors in newly diagnosed Type 2 diabetes: a mediational analysis.

PubMed

Hall, Peter A; Fong, Geoffrey T; Cheng, Alice Y

2012-12-01

The primary objective of the current study was to examine the extent to which domain-specific time perspective predicts weight management behaviors (dietary behavior and physical activity) among those newly diagnosed with Type 2 diabetes. A secondary objective was to test potential mediators of the hypothesized effect (behavioral intention, self-efficacy and control beliefs). A total of 204 adults newly diagnosed (≤6 months) with Type 2 diabetes participated in the study, which included a baseline assessment of domain-general and domain-specific time perspective, as well as strength of intention to perform two weight-management behaviors (dietary choice and physical activity); both weight-management behaviors were assessed again at 6 month follow-up. Hierarchical multiple regression analyses revealed a prospective association between domain-specific time perspective and uptake of weight management behaviors. Individuals with newly diagnosed T2DM possessing a future-oriented time perspective reported making less frequent fatty food choices and greater increases in physical activity over the 6-month follow-up interval. These effects were selectively mediated by intention strength, and not competing social cognitive variables. For both behaviors, the total effects and meditational models were robust to adjustments for demographics, body composition and disease variables. A future-oriented time perspective is prospectively associated with superior uptake of weight management behaviors among those with newly diagnosed Type 2 diabetes. The facilitating effect of future-oriented thinking appears to occur via enhanced strength of intentions to perform weight management behaviors.