Self-Efficacy and Social Support as Mediators Between Culturally Specific Dance and Lifestyle Physical Activity

PubMed Central

Murrock, Carolyn J.; Madigan, Elizabeth

2013-01-01

Culturally specific dance has the potential to generate health benefits but is seldom used even among studies advocating culturally specific interventions. This study examined the components of self-efficacy and social support as mediators between culturally specific dance and lifestyle physical activity in African American women (N = 126). An experimental design compared intervention and control groups for mediating effects of self-efficacy and social support on lifestyle physical activity. Findings indicated that only outcome expectations and social support from friends mediated effects. Culturally specific dance is a first step in encouraging African American women to become more physically active and improve health outcomes. The implications are that culturally specific dance programs can improve health outcomes by including members of underserved populations. PMID:18763475

Self-efficacy and social support as mediators between culturally specific dance and lifestyle physical activity.

PubMed

Murrock, Carolyn J; Madigan, Elizabeth

2008-01-01

Culturally specific dance has the potential to generate health benefits but is seldom used even among studies advocating culturally specific interventions. This study examined the components of self-efficacy and social support as mediators between culturally specific dance and lifestyle physical activity in African American women (N = 126). An experimental design compared intervention and control groups for mediating effects of self-efficacy and social support on lifestyle physical activity. Findings indicated that only outcome expectations and social support from friends mediated effects. Culturally specific dance is a first step in encouraging African American women to become more physically active and improve health outcomes. The implications are that culturally specific dance programs can improve health outcomes by including members of underserved populations.

Are flexibility and muscle-strengthening activities associated with a higher risk of developing low back pain?

PubMed Central

Sandler, Robert D.; Sui, Xuemei; Church, Timothy S.; Fritz, Stacy L.; Beattie, Paul F.; Blair, Steven N.

2013-01-01

Objective To examine the association between participation in flexibility or muscle-strengthening activities with the development of low back pain (LBP). Design Observational cohort study. Methods The cohort included 4,610 adults, 17% female, between 20 and 81 years of age (mean 46.6, s.d. 4.96). The cohort was followed for a mean of 4.9 years for self-reported LBP. All participants reported at baseline whether they performed flexibility or muscle-strengthening activities, including specific sub-types. Results Neither general performance of flexibility or muscle-strengthening activities were associated with a higher incidence of LBP compared to those who did not perform these activities. Those who reported stretching, as a specific flexibility activity were at a higher risk of developing LBP compared with those who performed no flexibility exercises, reported calisthenic flexibility activities, or attended exercise classes. Those who reported using weight training machines, as part of muscle-strengthening activities, had a higher risk of reporting LBP, compared with those who did not perform muscle-strengthening activities or performed calisthenic or free weight activities. Conclusion In this sample, stretching or use of weight training machines is associated with increased risk of developing LBP compared to use of free weights, calisthenics or flexibility classes. PMID:23988784

A randomized controlled trial of an activity specific exercise program for individuals with Alzheimer disease in long-term care settings.

PubMed

Roach, Kathryn E; Tappen, Ruth M; Kirk-Sanchez, Neva; Williams, Christine L; Loewenstein, David

2011-01-01

To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Randomized, controlled, single-blinded clinical trial. Residents of 7 long-term care facilities. Eighty-two long-term care residents with mild to severe AD. An activity specific exercise program was compared to a walking program and to an attention control. Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined.

Ride specification review for the Montana Department of Transportation

DOT National Transportation Integrated Search

2006-08-01

This report covers the activities that were performed to enhance the current Montana Department of Transportation (MDT)ride specification for flexible pavements. The project team reviewed the MDT ride specification for flexible pavements and compared...

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

Does arthroscopic rotator cuff repair improve patients' activity levels?

PubMed

Baumgarten, Keith M; Chang, Peter S; Dannenbring, Tasha M; Foley, Elaine K

2018-06-04

Rotator cuff repair decreases pain, improves range of motion, and increases strength. Whether these improvements translate to an improvement in a patient's activity level postoperatively remains unknown. The Shoulder Activity Level is a valid and reliable outcomes survey that can be used to measure a patient's shoulder-specific activity level. Currently, there are no studies that examine the effect of rotator cuff repair on shoulder activity level. Preoperative patient-determined outcomes scores collected prospectively on patients undergoing rotator cuff repair were compared with postoperative scores at a minimum of 2 years. These scores included the Shoulder Activity Level, Western Ontario Rotator Cuff Index, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, and simple shoulder test. Inclusion criteria were patients undergoing arthroscopic rotator cuff repair. Included were 281 shoulders from 273 patients with a mean follow-up of 3.7 years. The postoperative median Western Ontario Rotator Cuff Index (42 vs. 94), American Shoulder and Elbow Surgeons (41 vs. 95), Single Assessment Numeric Evaluation (30 vs. 95), and simple shoulder test (4 vs. 11) scores were statistically significantly improved compared with preoperative scores (P < .0001). The postoperative median Shoulder Activity Level score decreased compared with the preoperative score (12 vs. 11; P < .0001). Patients reported a statistically significant deterioration of their Shoulder Activity Level score after rotator cuff repair compared with their preoperative scores, although disease-specific and joint-specific quality of life scores all had statistically significantly improvement. This study suggests that patients generally have (1) significant improvements in their quality of life and (2) small deteriorations in activity level after arthroscopic rotator cuff repair. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

PubMed

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

PubMed Central

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. PMID:29320502

Comparing brain activity patterns during spontaneous exploratory and cue-instructed learning using single photon-emission computed tomography (SPECT) imaging of regional cerebral blood flow in freely behaving rats.

PubMed

Mannewitz, A; Bock, J; Kreitz, S; Hess, A; Goldschmidt, J; Scheich, H; Braun, Katharina

2018-05-01

Learning can be categorized into cue-instructed and spontaneous learning types; however, so far, there is no detailed comparative analysis of specific brain pathways involved in these learning types. The aim of this study was to compare brain activity patterns during these learning tasks using the in vivo imaging technique of single photon-emission computed tomography (SPECT) of regional cerebral blood flow (rCBF). During spontaneous exploratory learning, higher levels of rCBF compared to cue-instructed learning were observed in motor control regions, including specific subregions of the motor cortex and the striatum, as well as in regions of sensory pathways including olfactory, somatosensory, and visual modalities. In addition, elevated activity was found in limbic areas, including specific subregions of the hippocampal formation, the amygdala, and the insula. The main difference between the two learning paradigms analyzed in this study was the higher rCBF observed in prefrontal cortical regions during cue-instructed learning when compared to spontaneous learning. Higher rCBF during cue-instructed learning was also observed in the anterior insular cortex and in limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes showed hemispheric lateralization. Taken together, our study is the first to compare partly lateralized brain activity patterns during two different types of learning.

Molybdenum and vanadium do not replace tungsten in the catalytically active forms of the three tungstoenzymes in the hyperthermophilic archaeon Pyrococcus furiosus.

PubMed Central

Mukund, S; Adams, M W

1996-01-01

Three different types of tungsten-containing enzyme have been previously purified from Pyrococcus furiosus (optimum growth temperature, 100 degrees C): aldehyde ferredoxin oxidoreductase (AOR), formaldehyde ferredoxin oxidoreductase (FOR), and glyceraldehyde-3-phosphate oxidoreductase (GAPOR). In this study, the organism was grown in media containing added molybdenum (but not tungsten or vanadium) or added vanadium (but not molybdenum or tungsten). In both cell types, there were no dramatic changes compared with cells grown with tungsten, in the specific activities of hydrogenase, ferredoxin:NADP oxidoreductase, or the 2-keto acid ferredoxin oxidoreductases specific for pyruvate, indolepyruvate, 2-ketoglutarate, and 2-ketoisovalerate. Compared with tungsten-grown cells, the specific activities of AOR, FOR, and GAPOR were 40, 74, and 1%, respectively, in molybdenum-grown cells, and 7, 0, and 0%, respectively, in vanadium-grown cells. AOR purified from vanadium-grown cells lacked detectable vanadium, and its tungsten content and specific activity were both ca. 10% of the values for AOR purified from tungsten-grown cells. AOR and FOR purified from molybdenum-grown cells contained no detectable molybdenum, and their tungsten contents and specific activities were > 70% of the values for the enzymes purified from tungsten-grown cells. These results indicate that P. furiosus uses exclusively tungsten to synthesize the catalytically active forms of AOR, FOR, and GAPOR, and active molybdenum- or vanadium-containing isoenzymes are not expressed when the cells are grown in the presence of these other metals. PMID:8550411

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

In vitro autoradiographic localization of angiotensin-converting enzyme in sarcoid lymph nodes

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

Allen, R.K.; Chai, S.Y.; Dunbar, M.S.

1986-09-01

Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, /sup 125/I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosismore » had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.« less

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.

Parsing the Passive: Comparing Children with Specific Language Impairment to Sequential Bilingual Children

ERIC Educational Resources Information Center

Marinis, Theodoros; Saddy, Douglas

2013-01-01

Twenty-five monolingual (L1) children with specific language impairment (SLI), 32 sequential bilingual (L2) children, and 29 L1 controls completed the Test of Active & Passive Sentences-Revised (van der Lely 1996) and the Self-Paced Listening Task with Picture Verification for actives and passives (Marinis 2007). These revealed important…

Growth, sucrose synthase, and invertase activities of developing Phaseolus vulgaris L. fruits

Treesearch

Shi-Jean S. Sung; W.J. Sheih; D.R. Geiger; C.C. Black

1994-01-01

Activities of sucrose-cleaving enzymes, acid and neutral invertase and sucrose synthase, were measured in pods and seeds of developing snap bean (Phaseolus vulgaris L.) fruits, and compared with 14C-import, elongation and dry weight accumulation. The data supports the association of specific sucrose-cleaving enzymes with the specific processes that occur in the...

Exploration of the benefits of an activity-specific test of temperament.

PubMed

Trofimova, Irina N

2009-10-01

The Structure of Temperament Questionnaire (STQ) was proposed by Rusalov in 1989 and subsequently tested in five languages. The questionnaire assesses four temperamental traits (Ergonicity, Plasticity, Tempo, and Emotionality) in three separate areas of activity: physical, verbal-social, and intellectual. The scales are all activity-specific. In 775 Canadian subjects, two temperament tests were compared, both developed on the basis of Pavlovian studies of the nervous system: the activity-specific approach (STQ) and the nonspecific Pavlovian Temperamental Survey (PTS). More significant sex differences were found on activity-specific scales of the STQ than on the nonspecific PTS scales. The pattern of correlations between the STQ scales and the time taken on an experimental task requiring a prolonged and intense word-assessment activity showed stronger correlations with the specific scales of the STQ measuring the dynamic aspects of social-verbal activity, and not with the PTS Strength of Excitation scale, which is based on a "general arousal" concept. The results supported the separation of temperament traits related to three different types of activities and opposed to "general arousal" theories of temperament.

FMRI Brain Activation in a Finnish Family with Specific Language Impairment Compared with a Normal Control Group

ERIC Educational Resources Information Center

Hugdahl, Kenneth; Gundersen, Hilde; Brekke, Cecilie; Thomsen, Tormod; Rimol, Lars Morten; Ersland, Lars; Niemi, Jussi

2004-01-01

The aim of the present study was to investigate differences in brain activation in a family with SLI as compared to intact individuals with normally developed language during processing of language stimuli. Functional magnetic resonance imaging (fMRI) was used to monitor changes in neuronal activation in temporal and frontal lobe areas in 5…

Analysis of Phosphorylation of the Receptor-Like Protein Kinase HAESA during Arabidopsis Floral Abscission

PubMed Central

Taylor, Isaiah; Wang, Ying; Seitz, Kati; Baer, John; Bennewitz, Stefan; Mooney, Brian P.; Walker, John C.

2016-01-01

Receptor-like protein kinases (RLKs) are the largest family of plant transmembrane signaling proteins. Here we present functional analysis of HAESA, an RLK that regulates floral organ abscission in Arabidopsis. Through in vitro and in vivo analysis of HAE phosphorylation, we provide evidence that a conserved phosphorylation site on a region of the HAE protein kinase domain known as the activation segment positively regulates HAE activity. Additional analysis has identified another putative activation segment phosphorylation site common to multiple RLKs that potentially modulates HAE activity. Comparative analysis suggests that phosphorylation of this second activation segment residue is an RLK specific adaptation that may regulate protein kinase activity and substrate specificity. A growing number of RLKs have been shown to exhibit biologically relevant dual specificity toward serine/threonine and tyrosine residues, but the mechanisms underlying dual specificity of RLKs are not well understood. We show that a phospho-mimetic mutant of both HAE activation segment residues exhibits enhanced tyrosine auto-phosphorylation in vitro, indicating phosphorylation of this residue may contribute to dual specificity of HAE. These results add to an emerging framework for understanding the mechanisms and evolution of regulation of RLK activity and substrate specificity. PMID:26784444

Relative Contributions of Specific Activity Histories and Spontaneous Processes to Size Remodeling of Glutamatergic Synapses

PubMed Central

Dvorkin, Roman; Ziv, Noam E.

2016-01-01

The idea that synaptic properties are defined by specific pre- and postsynaptic activity histories is one of the oldest and most influential tenets of contemporary neuroscience. Recent studies also indicate, however, that synaptic properties often change spontaneously, even in the absence of specific activity patterns or any activity whatsoever. What, then, are the relative contributions of activity history-dependent and activity history-independent processes to changes synapses undergo? To compare the relative contributions of these processes, we imaged, in spontaneously active networks of cortical neurons, glutamatergic synapses formed between the same axons and neurons or dendrites under the assumption that their similar activity histories should result in similar size changes over timescales of days. The size covariance of such commonly innervated (CI) synapses was then compared to that of synapses formed by different axons (non-CI synapses) that differed in their activity histories. We found that the size covariance of CI synapses was greater than that of non-CI synapses; yet overall size covariance of CI synapses was rather modest. Moreover, momentary and time-averaged sizes of CI synapses correlated rather poorly, in perfect agreement with published electron microscopy-based measurements of mouse cortex synapses. A conservative estimate suggested that ~40% of the observed size remodeling was attributable to specific activity histories, whereas ~10% and ~50% were attributable to cell-wide and spontaneous, synapse-autonomous processes, respectively. These findings demonstrate that histories of naturally occurring activity patterns can direct glutamatergic synapse remodeling but also suggest that the contributions of spontaneous, possibly stochastic, processes are at least as great. PMID:27776122

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

A Randomized Controlled Trial of an Activity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings

PubMed Central

Roach, Kathryn E.; Tappen, Ruth M.; Kirk-Sanchez, Neva; Williams, Christine L.; Loewenstein, David

2011-01-01

Objective To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Design Randomized, controlled, single-blinded clinical trial. Setting Residents of 7 long-term care facilities. Participants Eighty-two long-term care residents with mild to severe AD. Intervention An activity specific exercise program was compared to a walking program and to an attention control. Measurements Ability to perform bed mobility and transfers were assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Results Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined. PMID:21937893

Context-Specific Outdoor Time and Physical Activity among School-Children Across Gender and Age: Using Accelerometers and GPS to Advance Methods

PubMed Central

Klinker, Charlotte Demant; Schipperijn, Jasper; Kerr, Jacqueline; Ersbøll, Annette Kjær; Troelsen, Jens

2014-01-01

Introduction: Being outdoors has a positive influence on health among children. Evidence in this area is limited and many studies have used self-reported measures. Objective context-specific assessment of physical activity patterns and correlates, such as outdoor time, may progress this field. Aims: To employ novel objective measures to assess age and gender differences in context-specific outdoor weekday behavior patterns among school-children [outdoor time and outdoor moderate to vigorous physical activity (MVPA)] and to investigate associations between context-specific outdoor time and MVPA. Methods: A total of 170 children had at least one weekday of 9 h combined accelerometer and global positioning system data and were included in the analyses. The data were processed using the personal activity and location measurement system (PALMS) and a purpose-built PostgreSQL database resulting in context-specific measures for outdoor time, outdoor MVPA, and overall daily MVPA. In addition, 4 domains (leisure, school, transport, and home) and 11 subdomains (e.g., urban green space and sports facilities) were created and assessed. Multilevel analyses provided results on age and gender differences and the association between outdoor time and MVPA. Results: Girls compared to boys had fewer outdoor minutes (p < 0.05), spent a smaller proportion of their overall daily time outdoors (p < 0.05), had fewer outdoor MVPA minutes during the day (p < 0.001) and in 11 contexts. Children compared to adolescents had more outdoor minutes (p < 0.05). During school and within recess, children compared to adolescents had more outdoor MVPA (p < 0.001) and outdoor time (p < 0.001). A 1-h increase in outdoor time was associated with 9.9 more minutes of MVPA (p < 0.001). Conclusion: A new methodology to assess the context-specific outdoor time and physical activity patterns has been developed and can be expanded to other populations. Different context-specific patterns were found for gender and age, suggesting different strategies may be needed to promote physical activity. PMID:24653983

Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.

PubMed

Yoon, Kyoung Jin P; Krull, Erik J; Morton, Christopher L; Bornmann, William G; Lee, Richard E; Potter, Philip M; Danks, Mary K

2003-11-01

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan, CPT-11) is a camptothecin prodrug that is metabolized by carboxylesterases (CE) to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), a topoisomerase I inhibitor. CPT-11 has shown encouraging antitumor activity against a broad spectrum of tumor types in early clinical trials, but hematopoietic and gastrointestinal toxicity limit its administration. To increase the therapeutic index of CPT-11 and to develop other prodrug analogues for enzyme/prodrug gene therapy applications, our laboratories propose to develop camptothecin prodrugs that will be activated by specific CEs. Specific analogues might then be predicted to be activated, for example, predominantly by human liver CE(hCE1), by human intestinal CE (hiCE), or in gene therapy approaches using a rabbit liver CE (rCE). This study describes a molecular modeling approach to relate the structure of rCE-activated camptothecin prodrugs with their biological activation. Comparative molecular field analysis, comparative molecular similarity index analysis, and docking studies were used to predict the biological activity of a 4-benzylpiperazine derivative of CPT-11 [7-ethyl-10-[4-(1-benzyl)-1-piperazino]carbonyloxycamptothecin (BP-CPT)] in U373MG glioma cell lines transfected with plasmids encoding rCE or hiCE. BP-CPT has been reported to be activated more efficiently than CPT-11 by a rat serum esterase activity; however, three-dimensional quantitative structure-activity relationship studies predicted that rCE would activate BP-CPT less efficiently than CPT-11. This was confirmed by both growth inhibition experiments and kinetic studies. The method is being used to design camptothecin prodrugs predicted to be activated by specific CEs.

A systematic review of job-specific workers' health surveillance activities for fire-fighting, ambulance, police and military personnel.

PubMed

Plat, M J; Frings-Dresen, M H W; Sluiter, J K

2011-12-01

Some occupations have tasks and activities that require monitoring safety and health aspects of the job; examples of such occupations are emergency services personnel and military personnel. The two objectives of this systematic review were to describe (1) the existing job-specific workers' health surveillance (WHS) activities and (2) the effectiveness of job-specific WHS interventions with respect to work functioning, for selected jobs. The search strategy systematically searched the PubMed, PsycINFO and OSH-update databases. The search strategy consisted of several synonyms of the job titles of interest, combined with synonyms for workers' health surveillance. The methodological quality was checked. At least one study was found for each of the following occupations fire fighters, ambulance personnel, police personnel and military personnel. For the first objective, 24 studies described several job-specific WHS activities aimed at aspects of psychological, 'physical' (energetic, biomechanical and balance), sense-related, environmental exposure or cardiovascular requirements. The seven studies found for the second objective measured different outcomes related to work functioning. The methodological quality of the interventions varied, but with the exception of one study, all scored over 55% of the maximum score. Six studies showed effectiveness on at least some of the defined outcomes. The studies described several job-specific interventions: a trauma resilience training, healthy lifestyle promotion, physical readiness training, respiratory muscle training, endurance and resistance training, a physical exercise programme and comparing vaccines. Several examples of job-specific WHS activities were found for the four occupations. Compared to studies focusing on physical tasks, a few studies were found that focus on psychological tasks. Effectiveness studies for job-specific WHS interventions were scarce, although their results were promising. We recommend studying job-specific WHS in effectiveness studies.

Experiences and Perceptions of Physical Activity Among South Asian and Anglo-Australians With Type 2 Diabetes or Cardiovascular Disease: Implications for Clinical Practice.

PubMed

Gupta, Sabrina S; Aroni, Rosalie; Teede, Helena

2017-02-01

Research indicates that there are worryingly low levels of physical activity among South Asians compared with Anglo-Australians with type 2 diabetes and/or cardiovascular disease (CVD). We compared perceptions, barriers, and enablers of physical activity in these groups. We used a qualitative design, conducting in-depth, semistructured iterative interviews in Victoria with 57 South Asian and Anglo-Australian participants with either type 2 diabetes or CVD. While both groups exhibited knowledge of the value of physical activity in health maintenance and disease management, they wished for more specific and culturally tailored advice from clinicians about the type, duration, and intensity of physical activity required. Physical activity identities were tied to ethnic identities, with members of each group aspiring to meet the norms of their culture regarding engagement with physical activity as specific exercise or as incidental exercise. Individual personal exercise was deemed important by Anglo-Australians whereas South Asians preferred family-based physical activity.

Comparative Normal/Failing Rat Myocardium Cell Membrane Chromatographic Analysis System for Screening Specific Components That Counteract Doxorubicin-Induced Heart Failure from Acontium carmichaeli

PubMed Central

2015-01-01

Cell membrane chromatography (CMC) derived from pathological tissues is ideal for screening specific components acting on specific diseases from complex medicines owing to the maximum simulation of in vivo drug-receptor interactions. However, there are no pathological tissue-derived CMC models that have ever been developed, as well as no visualized affinity comparison of potential active components between normal and pathological CMC columns. In this study, a novel comparative normal/failing rat myocardium CMC analysis system based on online column selection and comprehensive two-dimensional (2D) chromatography/monolithic column/time-of-flight mass spectrometry was developed for parallel comparison of the chromatographic behaviors on both normal and pathological CMC columns, as well as rapid screening of the specific therapeutic agents that counteract doxorubicin (DOX)-induced heart failure from Acontium carmichaeli (Fuzi). In total, 16 potential active alkaloid components with similar structures in Fuzi were retained on both normal and failing myocardium CMC models. Most of them had obvious decreases of affinities on failing myocardium CMC compared with normal CMC model except for four components, talatizamine (TALA), 14-acetyl-TALA, hetisine, and 14-benzoylneoline. One compound TALA with the highest affinity was isolated for further in vitro pharmacodynamic validation and target identification to validate the screen results. Voltage-dependent K+ channel was confirmed as a binding target of TALA and 14-acetyl-TALA with high affinities. The online high throughput comparative CMC analysis method is suitable for screening specific active components from herbal medicines by increasing the specificity of screened results and can also be applied to other biological chromatography models. PMID:24731167

Anticipating agoraphobic situations: the neural correlates of panic disorder with agoraphobia.

PubMed

Wittmann, A; Schlagenhauf, F; Guhn, A; Lueken, U; Gaehlsdorf, C; Stoy, M; Bermpohl, F; Fydrich, T; Pfleiderer, B; Bruhn, H; Gerlach, A L; Kircher, T; Straube, B; Wittchen, H-U; Arolt, V; Heinz, A; Ströhle, A

2014-08-01

Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia. We compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm). During the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures. This study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.

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.

Improved composite targets for small scale 64Cu production comparing Au- and Pt-foils as 64Ni backing

NASA Astrophysics Data System (ADS)

Walther, M.; Preusche, S.; Fuechtner, F.; Pietzsch, H. J.; Steinbach, J.

2012-12-01

Advantages of a stacked assembly of target support components for 64Cu production via 64Ni(p,n)64Cu reaction were reported recently. The present work shows the applicability of these composite targets for beam currents up to 22 μA. Gold and platinum foils were evaluated as 64Ni backing. The effective specific activity (ESA) and specific activity (SA) were determined by TETA titration at room temperature and at 80 °C and compared with additional copper quantification results via ICP-MS and stripping voltammetric trace analysis (VA).

Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

ERIC Educational Resources Information Center

de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

2011-01-01

Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

Using WebQuests to Teach Content: Comparing Instructional Strategies

ERIC Educational Resources Information Center

Strickland, Janet

2005-01-01

The purpose of this study was to compare the use of WebQuests with traditional instruction. Specifically, the study examined the end-of-unit exam scores for students who completed a WebQuest on the Texas Revolution and those students completing a poster activity. Both of the instructional activities were implemented as additional enhancement to…

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

PubMed

George, M S; Anton, R F; Bloomer, C; Teneback, C; Drobes, D J; Lorberbaum, J P; Nahas, Z; Vincent, D J

2001-04-01

Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

An exploratory study of physical activity and perceived barriers to exercise in ambulant people with neuromuscular disease compared with unaffected controls.

PubMed

Phillips, Margaret; Flemming, Nicola; Tsintzas, Kostas

2009-08-01

To determine activity patterns and perceived barriers to exercise in ambulant people with neuromuscular disease compared with ambulatory controls. Prospective controlled parallel group design. Outpatient clinic and community. Thirteen ambulatory people with neuromuscular disease and 18 ambulatory controls. Heart rates were recorded during sedentary activity and treadmill walking at various speeds to indicate activity threshold (flex heart rate), followed by ambulatory heart rate monitoring over two weekdays and one weekend day. The EPIC-Norfolk Physical Activity Questionnaire-2 and Barriers to Physical Activity and Disability Survey were completed. Participants with neuromuscular disease were less active than controls as estimated by both the EPIC-Norfolk Physical Activity Questionnaire-2, P<0.004, and the flex heart rate method, P<0.05. The number of perceived barriers was greater in the neuromuscular group, a mean of 7 (SD 4.2) barriers, compared with mean 3 (SD 2.1) barriers for controls, P<0.05. Specific barriers differed, with the barriers of 'pain', 'lack of energy' and 'exercise is too difficult' showing the greatest discrepancy and being higher in the neuromuscular disease group. Physical activity, as determined by two different methods, was less and barriers to exercise greater in people with neuromuscular disease compared with healthy controls. Specific barriers were different in the two groups. This information could assist in the design of achievable and effective exercise programmes for people with neuromuscular disease.

Mesoporous carbon-supported Pd nanoparticles with high specific surface area for cyclohexene hydrogenation: Outstanding catalytic activity of NaOH-treated catalysts

NASA Astrophysics Data System (ADS)

Puskás, R.; Varga, T.; Grósz, A.; Sápi, A.; Oszkó, A.; Kukovecz, Á.; Kónya, Z.

2016-06-01

Extremely high specific surface area mesoporous carbon-supported Pd nanoparticle catalysts were prepared with both impregnation and polyol-based sol methods. The silica template used for the synthesis of mesoporous carbon was removed by both NaOH and HF etching. Pd/mesoporous carbon catalysts synthesized with the impregnation method has as high specific surface area as 2250 m2/g. In case of NaOH-etched impregnated samples, the turnover frequency of cyclohexene hydrogenation to cyclohexane at 313 K was obtained 14 molecules • site- 1 • s- 1. The specific surface area of HF-etched samples was higher compared to NaOH-etched samples. However, catalytic activity was 3-6 times higher on NaOH-etched samples compared to HF-etched samples, which can be attributed to the presence of sodium and surface hydroxylgroups of the catalysts etched with NaOH solution.

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.

Balance, dizziness and proprioception in patients with chronic whiplash associated disorders complaining of dizziness: A prospective randomized study comparing three exercise programs.

PubMed

Treleaven, Julia; Peterson, Gunnel; Ludvigsson, Maria Landén; Kammerlind, Ann-Sofi; Peolsson, Anneli

2016-04-01

Dizziness and unsteadiness are common symptoms following a whiplash injury. To compare the effect of 3 exercise programs on balance, dizziness, proprioception and pain in patients with chronic whiplash complaining of dizziness. A sub-analysis of a randomized study. One hundred and forty subjects were randomized to either a physiotherapist-guided neck-specific exercise (NSE), physiotherapist-guided neck-specific exercise, with a behavioural approach (NSEB) or prescription of general physical activity (PPA) group. Pre intervention, 3, 6 and 12 months post baseline they completed the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ), Visual Analogue Scales (VAS) for, dizziness at rest and during activity and physical measures (static and dynamic clinical balance tests and head repositioning accuracy (HRA)). There were significant time by group differences with respect to dizziness during activity and UCLA-Q favouring the physiotherapy led neck specific exercise group with a behavioural approach. Within group analysis of changes over time also revealed significant changes in most variables apart from static balance. Between and within group comparisons suggest that physiotherapist led neck exercise groups including a behavioural approach had advantages in improving measures of dizziness compared with the general physical activity group, although many still complained of dizziness and balance impairment. Future studies should consider exercises specifically designed to address balance, dizziness and cervical proprioception in those with persistent whiplash. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

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.

Visual Space and Object Space in the Cerebral Cortex of Retinal Disease Patients

PubMed Central

Spileers, Werner; Wagemans, Johan; Op de Beeck, Hans P.

2014-01-01

The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings). This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration), and a patient where input to the peripheral retina is lost (retinitis pigmentosa). From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline) rather than relative activation (comparing different stimulus conditions). Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (de)activation is consistent with the retinal loss. PMID:24505449

Simultaneous Detection of Metalloprotease Activities in Complex Biological Samples Using the PrAMA (Proteolytic Activity Matrix Assay) Method.

PubMed

Conrad, Catharina; Miller, Miles A; Bartsch, Jörg W; Schlomann, Uwe; Lauffenburger, Douglas A

2017-01-01

Proteolytic Activity Matrix Analysis (PrAMA) is a method for simultaneously determining the activities of specific Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs) in complex biological samples. In mixtures of unknown proteases, PrAMA infers selective metalloproteinase activities by using a panel of moderately specific FRET-based polypeptide protease substrates in parallel, typically monitored by a plate-reader in a 96-well format. Fluorescence measurements are then quantitatively compared to a standard table of catalytic efficiencies measured from purified mixtures of individual metalloproteinases and FRET substrates. Computational inference of specific activities is performed with an easily used Matlab program, which is provided herein. Thus, we describe PrAMA as a combined experimental and mathematical approach to determine real-time metalloproteinase activities, which has previously been applied to live-cell cultures, cellular lysates, cell culture supernatants, and body fluids from patients.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs.

PubMed

Keane, Fiona M; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G; Chowdhury, Sumaiya; Poplawski, Sarah E; Lai, Jack H; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M T; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M; McLennan, Susan V; McCaughan, Geoffrey W; Bachovchin, William W; Gorrell, Mark D

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs☆

PubMed Central

Keane, Fiona M.; Yao, Tsun-Wen; Seelk, Stefanie; Gall, Margaret G.; Chowdhury, Sumaiya; Poplawski, Sarah E.; Lai, Jack H.; Li, Youhua; Wu, Wengen; Farrell, Penny; Vieira de Ribeiro, Ana Julia; Osborne, Brenna; Yu, Denise M.T.; Seth, Devanshi; Rahman, Khairunnessa; Haber, Paul; Topaloglu, A. Kemal; Wang, Chuanmin; Thomson, Sally; Hennessy, Annemarie; Prins, John; Twigg, Stephen M.; McLennan, Susan V.; McCaughan, Geoffrey W.; Bachovchin, William W.; Gorrell, Mark D.

2013-01-01

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis. PMID:24371721

High sensitivity and specificity of a new functional flow cytometry assay for clinically significant heparin-induced thrombocytopenia antibodies.

PubMed

Garritsen, H S; Probst-Kepper, M; Legath, N; Eberl, W; Samaniego, S; Woudenberg, J; Schuitemaker, J H N; Kroll, H; Gurney, D A; Moore, G W; Zehnder, J L

2014-04-01

Heparin-induced thrombocytopenia (HIT) is a life-threatening condition, in which the anticoagulant heparin, platelet factor 4 (PF4), and platelet-activating antibodies form complexes with prothrombotic properties. Laboratory tests to support clinical diagnosis are subdivided into functional, platelet activation assays, which lack standardization, or immunological assays, which have moderate specificity toward HIT. In this study, clinical performance of HITAlert, a novel in vitro diagnostic (IVD) registered platelet activation assay, was tested in a large cohort of HIT-suspected patients and compared with immunological assays. From 346 HIT-suspected patients (single center), clinical data including 4T pretest probability results, citrated platelet-poor plasmas, and sera were collected, allowing direct comparison of clinical observations with HITAlert results. HITAlert performance was compared with PF4 IgG ELISA (246 patients, three centers) and PF4 PaGIA (298 patients, single center). HITAlert showed high sensitivity (88.2%) and specificity (99.1%) when compared with clinical diagnosis. Agreement of HITAlert with PF4 ELISA- and PF4 PaGIA-positive patients is low (52.7 and 23.2%, respectively), while agreement with PF4 IgG ELISA- and PF4 PaGIA-negative patients is very high (98.1 and 99.1%, respectively). HITAlert performance is excellent when compared with clinical HIT diagnosis, making it a suitable assay for rapid testing of platelet activation due to anticoagulant therapy. © 2013 John Wiley & Sons Ltd.

Structural prediction and comparative docking studies of psychrophilic β- Galactosidase with lactose, ONPG and PNPG against its counter parts of mesophilic and thermophilic enzymes.

PubMed

Kumar, Ponnada Suresh; Pulicherla, Kk; Ghosh, Mrinmoy; Kumar, Anmol; Rao, Krs Sambasiva

2011-01-01

Enzymes from psychrophiles catalyze the reactions at low temperatures with higher specific activity. Among all the psychrophilic enzymes produced, cold active β-galactosidase from marine psychrophiles revalorizes a new arena in numerous areas at industrial level. The hydrolysis of lactose in to glucose and galactose by cold active β-galactosidase offers a new promising approach in removal of lactose from milk to overcome the problem of lactose intolerance. Herein we propose, a 3D structure of cold active β-galactosidase enzyme sourced from Pseudoalteromonas haloplanktis by using Modeler 9v8 and best model was developed having 88% of favourable region in ramachandran plot. Modelling was followed by docking studies with the help of Auto dock 4.0 against the three substrates lactose, ONPG and PNPG. In addition, comparative docking studies were also performed for the 3D model of psychrophilic β-galactosidase with mesophilic and thermophilic enzymes. Docking studies revealed that binding affinity of enzyme towards the three different substrates is more for psychrophilic enzyme when compared with mesophilic and thermophilic enzymes. It indicates that the enzyme has high specific activity at low temperature when compared with mesophilic and thermophilic enzymes.

Different specificities of two aldehyde dehydrogenases from Saccharomyces cerevisiae var. boulardii.

PubMed

Datta, Suprama; Annapure, Uday S; Timson, David J

2017-04-30

Aldehyde dehydrogenases play crucial roles in the detoxification of exogenous and endogenous aldehydes by catalysing their oxidation to carboxylic acid counterparts. The present study reports characterization of two such isoenzymes from the yeast Saccharomyces cerevisiae var. boulardii (NCYC 3264), one mitochondrial (Ald4p) and one cytosolic (Ald6p). Both Ald4p and Ald6p were oligomeric in solution and demonstrated positive kinetic cooperativity towards aldehyde substrates. Wild-type Ald6p showed activity only with aliphatic aldehydes. Ald4p, on the contrary, showed activity with benzaldehyde along with a limited range of aliphatic aldehydes. Inspection of modelled structure of Ald6p revealed that a bulky amino acid residue (Met 177 , compared with the equivalent residue Leu 196 in Ald4p) might cause steric hindrance of cyclic substrates. Therefore, we hypothesized that specificities of the two isoenzymes towards aldehyde substrates were partly driven by steric hindrance in the active site. A variant of wild-type Ald6p with the Met 177 residue replaced by a valine was also characterized to address to the hypothesis. It showed an increased specificity range and a gain of activity towards cyclohexanecarboxaldehyde. It also demonstrated an increased thermal stability when compared with both the wild-types. These data suggest that steric bulk in the active site of yeast aldehyde dehydrogenases is partially responsible for controlling specificity. © 2017 The Author(s).

Inter- and intra-specific competition of duckweed under multiple heavy metal contaminated water.

PubMed

Zhao, Zhao; Shi, Huijuan; Kang, Xianjiang; Liu, Cunqi; Chen, Lingci; Liang, Xiaofei; Jin, Lei

2017-11-01

The influences of intra- and inter-species competition on ecosystems are poorly understood. Lemna aequinoctialis and Spirodela polyrhiza were used to assess the effects of exposure to different concentrations of multiple heavy metals (copper-cadmium-zinc), when the plants were grown in mixed- or mono-culture. Parameters assessed included relative growth rate (RGR), content of chlorophyll, glutathione (GSH), malondialdehyde (MDA), as well as the activity of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD). Inter-specific competition was affected by metal concentration, with results indicating that inter-specific competition significantly affected duckweed growth and metal uptake in different heavy metal exposure conditions. Inter-specific competition increased growth rate of duckweed under high metal concentrations, although when compared with intra-specific competition, it caused no obvious differences under low metal concentrations. The growth of L. aequinoctialis was further increased in mixed culture when exposed to high metal concentrations, with inter-specific competition increasing the content of cadmium and zinc, while decreasing copper content of L. aequinoctialis compared with under intra-specific conditions. Conversely, inter-specific competition increased the content of copper and cadmium of S. polyrhiza, without causing obvious differences in zinc accumulation under high ambient concentrations. Under high metal conditions, inter-specific competition increased antioxidant enzyme activities in duckweed species, increasing resistance to heavy metals. Results show that inter-specific competition makes duckweed develop mechanisms to increase fitness and survival, such as enhancement of antioxidant enzyme activities, rather than limiting metal uptake when exposed to high concentrations of multiple metals. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

PubMed

Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

2016-01-01

Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

Depot-specific Regulation of the Conversion of Cortisone to Cortisol in Human Adipose Tissue

PubMed Central

Lee, Mi-Jeong; Fried, Susan K.; Mundt, Steven S.; Wang, Yanxin; Sullivan, Sean; Stefanni, Alice; Daugherty, Bruce L.; Hermanowski-Vosatka, Anne

2015-01-01

Objective Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue. Methods and Procedures Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity (3H-cortisone and 3H-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone. Results Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity. Discussion We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity. PMID:18388900

Changes in plasma chemistry after drug-induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica).

PubMed

Lumeij, J T; Meidam, M; Wolfswinkel, J; Van der Hage, M H; Dorrestein, G M

1988-01-01

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D-galactosamine (group B) and of muscle damage induced by doxycycline were compared. Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7-GT. Plasma AS AT activity was the most sensitive indicator of disease of the liver, but was not specific, since increased ASAT activities were also seen during muscle disease. ALAT activity was slightly more sensitive to liver damage than 7-GT, but was also not specific, being increased also after muscle damage. Plasma GLDH activity was increased only as a result of extensive liver necrosis. AP activity was of no value for detecting liver disease in the pigeon. CK activity was specific for muscle injury, though the activities of ALAT, ASAT and LD were also increased. Because of its long elimination half-life, increased ALAT activity persisted for 9 days after muscle damage, whereas CK activity returned to reference values within 3 days. LDH was a poor indicator of damage to liver and muscle, despite its relatively high tissue concentrations in both tissues. The rapid disappearance rate of LDH from plasma probably explains this observation.

Automatic detection of muscle activity from mechanomyogram signals: a comparison of amplitude and wavelet-based methods.

PubMed

Alves, Natasha; Chau, Tom

2010-04-01

Knowledge of muscle activity timing is critical to many clinical applications, such as the assessment of muscle coordination and the prescription of muscle-activated switches for individuals with disabilities. In this study, we introduce a continuous wavelet transform (CWT) algorithm for the detection of muscle activity via mechanomyogram (MMG) signals. CWT coefficients of the MMG signal were compared to scale-specific thresholds derived from the baseline signal to estimate the timing of muscle activity. Test signals were recorded from the flexor carpi radialis muscles of 15 able-bodied participants as they squeezed and released a hand dynamometer. Using the dynamometer signal as a reference, the proposed CWT detection algorithm was compared against a global-threshold CWT detector as well as amplitude-based event detection for sensitivity and specificity to voluntary contractions. The scale-specific CWT-based algorithm exhibited superior detection performance over the other detectors. CWT detection also showed good muscle selectivity during hand movement, particularly when a given muscle was the primary facilitator of the contraction. This may suggest that, during contraction, the compound MMG signal has a recurring morphological pattern that is not prevalent in the baseline signal. The ability of CWT analysis to be implemented in real time makes it a candidate for muscle-activity detection in clinical applications.

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

PubMed

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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,

Physical activity opportunities in Canadian childcare facilities: a provincial/territorial review of legislation.

PubMed

Vanderloo, Leigh M; Tucker, Patricia; Ismail, Ali; van Zandvroort, Melissa M

2012-05-01

Preschoolers spend a substantial portion of their day in childcare; therefore, these centers are an ideal venue to encourage healthy active behaviors. It is important that provinces'/territories' childcare legislation encourage physical activity (PA) opportunities. The purpose of this study was to review Canadian provincial/territorial childcare legislation regarding PA participation. Specifically, this review sought to 1) appraise each provincial/territorial childcare regulation for PA requirements, 2) compare such regulations with the NASPE PA guidelines, and 3) appraise these regulations regarding PA infrastructure. A review of all provincial/territorial childcare legislation was performed. Each document was reviewed separately by 2 researchers, and the PA regulations were coded and summarized. The specific provincial/territorial PA requirements (eg, type/frequency of activity) were compared with the NASPE guidelines. PA legislation for Canadian childcare facilities varies greatly. Eight of the thirteen provinces/territories provide PA recommendations; however, none provided specific time requirements for daily PA. All provinces/territories did require access to an outdoor play space. All Canadian provinces/territories lack specific PA guidelines for childcare facilities. The development, implementation, and enforcement of national PA legislation for childcare facilities may aid in tackling the childhood obesity epidemic and assist childcare staff in supporting and encouraging PA participation.

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.

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes

NASA Astrophysics Data System (ADS)

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M.; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-10-01

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03884g

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

PubMed

Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

2015-11-01

Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. Copyright © 2015. Published by Elsevier B.V.

Validation and Comparison of Accelerometers Worn on the Hip, Thigh, and Wrists for Measuring Physical Activity and Sedentary Behavior.

PubMed

Montoye, Alexander H K; Pivarnik, James M; Mudd, Lanay M; Biswas, Subir; Pfeiffer, Karin A

2016-01-01

Recent evidence suggests that physical activity (PA) and sedentary behavior (SB) exert independent effects on health. Therefore, measurement methods that can accurately assess both constructs are needed. To compare the accuracy of accelerometers placed on the hip, thigh, and wrists, coupled with machine learning models, for measurement of PA intensity category (SB, light-intensity PA [LPA], and moderate- to vigorous-intensity PA [MVPA]) and breaks in SB. Forty young adults (21 female; age 22.0 ± 4.2 years) participated in a 90-minute semi-structured protocol, performing 13 activities (three sedentary, 10 non-sedentary) for 3-10 minutes each. Participants chose activity order, duration, and intensity. Direct observation (DO) was used as a criterion measure of PA intensity category, and transitions from SB to a non-sedentary activity were breaks in SB. Participants wore four accelerometers (right hip, right thigh, and both wrists), and a machine learning model was created for each accelerometer to predict PA intensity category. Sensitivity and specificity for PA intensity category classification were calculated and compared across accelerometers using repeated measures analysis of variance, and the number of breaks in SB was compared using repeated measures analysis of variance. Sensitivity and specificity values for the thigh-worn accelerometer were higher than for wrist- or hip-worn accelerometers, > 99% for all PA intensity categories. Sensitivity and specificity for the hip-worn accelerometer were 87-95% and 93-97%. The left wrist-worn accelerometer had sensitivities and specificities of > 97% for SB and LPA and 91-95% for MVPA, whereas the right wrist-worn accelerometer had sensitivities and specificities of 93-99% for SB and LPA but 67-84% for MVPA. The thigh-worn accelerometer had high accuracy for breaks in SB; all other accelerometers overestimated breaks in SB. Coupled with machine learning modeling, the thigh-worn accelerometer should be considered when objectively assessing PA and SB.

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

Gender-specific activity demands experienced during semiprofessional basketball game play.

PubMed

Scanlan, Aaron T; Dascombe, Ben J; Kidcaff, Andrew P; Peucker, Jessica L; Dalbo, Vincent J

2015-07-01

To compare game activity demands between female and male semiprofessional basketball players. Female (n=12) and male (n=12) semiprofessional basketball players were monitored across 3 competitive games. Time-motion-analysis procedures quantified player activity into predefined movement categories across backcourt (BC) and frontcourt (FC) positions. Activity frequencies, durations, and distances were calculated relative to live playing time (min). Work:rest ratios were also calculated using the video data. Game activity was compared between genders for each playing position and all players. Female players performed at greater running work-rates than male players (45.7±1.4 vs. 42.1±1.7 m/min, P=.05), while male players performed more dribbling than female players (2.5±0.3 vs. 3.0±0.2 s/min; 8.4±0.3 vs. 9.7±0.7 m/min, P=.05). Positional analyses revealed that female BC players performed more low-intensity shuffling (P=.04) and jumping (P=.05), as well as longer (P=.04) jogging durations, than male BC players. Female FC players executed more upper-body activity (P=.03) and larger work:rest ratios (P<.001) than male FC players. No significant gender differences were observed in the overall intermittent demands, distance traveled, high-intensity shuffling activity, and sprinting requirements during game play. These findings indicate that gender-specific running and dribbling differences might exist in semiprofessional basketball. Furthermore, position-specific variations between female and male basketball players should be considered. These data may prove useful in the development of gender-specific conditioning plans relative to playing position in basketball.

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.

Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity.

PubMed

Speer, Colenso M; Sun, Chao; Liets, Lauren C; Stafford, Ben K; Chapman, Barbara; Cheng, Hwai-Jong

2014-11-07

Spontaneous retinal activity (SRA) is important during eye-specific segregation within the dorsal lateral geniculate nucleus (dLGN), but the feature(s) of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells (SACs) that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN. We induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes. Our data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high frequency RGC firing during bursts, and the number of spikes per RGC burst are each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An increase in the fraction of asynchronous spikes occurring outside of bursts and waves correlates with eye-specific segregation defects in studies reported to date. These findings highlight the relative importance of different features of SRA while providing additional constraints for computational models of Hebbian plasticity mechanisms in the developing visual system.

Effects of effluent from electoplating industry on the immune response in the freshwater fish, Cyprinus carpio.

PubMed

Borgia, V J Florence; Thatheyus, A J; Murugesan, A G; Alexander, S Catherine P; Geetha, I

2018-08-01

The present study was designed to assess the effect of sublethal concentrations of electoplating industry effluent (EIE) on the non-specific and specific immune responses in the freshwater fish, Cyprinus carpio. Sublethal concentrations of electroplating industry effluent such as 0.004, 0.007, 0.010 and 0.013% were chosen based on the LC 50 values. Experimental fish were exposed to these sublethal concentrations of EIE for 28 days. After 7, 14, 21 and 28 days of treatment, non-specific immune response by serum lysozyme activity, myeloperoxidase activity and antiprotease activity and specific immune response by antibody response to Aeromonas hydrophila using bacterial agglutination assay and ELISA were assessed. The results showed that chronic exposure of fish to 0.004, 0.007, 0.010 and 0.013% EIE, dose-dependently decreased the non-specific and specific immune responses on all the days tested compared to control fish whereas statistically significant suppressive effects were observed in fish exposed to 0.013% of EIE on all activities tested. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanistic Insights into Glucan Phosphatase Activity against Polyglucan Substrates*

PubMed Central

Meekins, David A.; Raththagala, Madushi; Auger, Kyle D.; Turner, Benjamin D.; Santelia, Diana; Kötting, Oliver; Gentry, Matthew S.; Vander Kooi, Craig W.

2015-01-01

Glucan phosphatases are central to the regulation of starch and glycogen metabolism. Plants contain two known glucan phosphatases, Starch EXcess4 (SEX4) and Like Sex Four2 (LSF2), which dephosphorylate starch. Starch is water-insoluble and reversible phosphorylation solubilizes its outer surface allowing processive degradation. Vertebrates contain a single known glucan phosphatase, laforin, that dephosphorylates glycogen. In the absence of laforin, water-soluble glycogen becomes insoluble, leading to the neurodegenerative disorder Lafora Disease. Because of their essential role in starch and glycogen metabolism glucan phosphatases are of significant interest, yet a comparative analysis of their activities against diverse glucan substrates has not been established. We identify active site residues required for specific glucan dephosphorylation, defining a glucan phosphatase signature motif (CζAGΨGR) in the active site loop. We further explore the basis for phosphate position-specific activity of these enzymes and determine that their diverse phosphate position-specific activity is governed by the phosphatase domain. In addition, we find key differences in glucan phosphatase activity toward soluble and insoluble polyglucan substrates, resulting from the participation of ancillary glucan-binding domains. Together, these data provide fundamental insights into the specific activity of glucan phosphatases against diverse polyglucan substrates. PMID:26231210

Design of aqueous redox-enhanced electrochemical capacitors with high specific energies and slow self-discharge.

PubMed

Chun, Sang-Eun; Evanko, Brian; Wang, Xingfeng; Vonlanthen, David; Ji, Xiulei; Stucky, Galen D; Boettcher, Shannon W

2015-08-04

Electrochemical double-layer capacitors exhibit high power and long cycle life but have low specific energy compared with batteries, limiting applications. Redox-enhanced capacitors increase specific energy by using redox-active electrolytes that are oxidized at the positive electrode and reduced at the negative electrode during charging. Here we report characteristics of several redox electrolytes to illustrate operational/self-discharge mechanisms and the design rules for high performance. We discover a methyl viologen (MV)/bromide electrolyte that delivers a high specific energy of ∼14 Wh kg(-1) based on the mass of electrodes and electrolyte, without the use of an ion-selective membrane separator. Substituting heptyl viologen for MV increases stability, with no degradation over 20,000 cycles. Self-discharge is low, due to adsorption of the redox couples in the charged state to the activated carbon, and comparable to cells with inert electrolyte. An electrochemical model reproduces experiments and predicts that 30-50 Wh kg(-1) is possible with optimization.

Design of aqueous redox-enhanced electrochemical capacitors with high specific energies and slow self-discharge

PubMed Central

Chun, Sang-Eun; Evanko, Brian; Wang, Xingfeng; Vonlanthen, David; Ji, Xiulei; Stucky, Galen D.; Boettcher, Shannon W.

2015-01-01

Electrochemical double-layer capacitors exhibit high power and long cycle life but have low specific energy compared with batteries, limiting applications. Redox-enhanced capacitors increase specific energy by using redox-active electrolytes that are oxidized at the positive electrode and reduced at the negative electrode during charging. Here we report characteristics of several redox electrolytes to illustrate operational/self-discharge mechanisms and the design rules for high performance. We discover a methyl viologen (MV)/bromide electrolyte that delivers a high specific energy of ∼14 Wh kg−1 based on the mass of electrodes and electrolyte, without the use of an ion-selective membrane separator. Substituting heptyl viologen for MV increases stability, with no degradation over 20,000 cycles. Self-discharge is low, due to adsorption of the redox couples in the charged state to the activated carbon, and comparable to cells with inert electrolyte. An electrochemical model reproduces experiments and predicts that 30–50 Wh kg−1 is possible with optimization. PMID:26239891

Hours spent and energy expended in physical activity domains: results from the Tomorrow Project cohort in Alberta, Canada.

PubMed

Csizmadi, Ilona; Lo Siou, Geraldine; Friedenreich, Christine M; Owen, Neville; Robson, Paula J

2011-10-10

Knowledge of adult activity patterns across domains of physical activity is essential for the planning of population-based strategies that will increase overall energy expenditure and reduce the risk of obesity and related chronic diseases. We describe domain-specific hours of activity and energy expended among participants in a prospective cohort in Alberta, Canada. The Past Year Total Physical Activity Questionnaire was completed by 15,591 Tomorrow Project® participants, between 2001 and 2005 detailing physical activity type, duration, frequency and intensity. Domain-specific hours of activity and activity-related energy expenditure, expressed as a percent of total energy expenditure (TEE) (Mean (SD); Median (IQR)) are reported across inactive (<1.4), low active (1.4 to 1.59), active (1.6 to 1.89) and very active (≥ 1.9) Physical Activity Level (PAL = TEE:REE) categories. In very active women and amongst all men except those classified as inactive, activity-related energy expenditure comprised primarily occupational activity. Amongst inactive men and women in active, low active and inactive groups, activity-related energy expenditure from household activity was comparable to, or exceeded that for occupational activity. Leisure-time activity-related energy expenditure decreased with decreasing PAL categories; however, even amongst the most active men and women it accounted for less than 10 percent of TEE. When stratified by employment status, leisure-time activity-related energy expenditure was greatest for retired men [mean (SD): 10.8 (8.5) percent of TEE], compared with those who were fully employed, employed part-time or not employed. Transportation-related activity was negligible across all categories of PAL and employment status. For the inactive portion of this population, active non-leisure activities, specifically in the transportation and occupational domains, need to be considered for inclusion in daily routines as a means of increasing population-wide activity levels. Environmental and policy changes to promote active transport and workplace initiatives could increase overall daily energy expenditure through reducing prolonged sitting time.

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

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.

Social Support and Leisure Time Physical Activity in Young Black Women

ERIC Educational Resources Information Center

Martin, Jasel

2018-01-01

Problem: Compared with other ethnic groups, Black women are the least likely group to engage in the recommended amount of physical activity. However, few studies have specifically identified or addressed barriers to physical activity in Black college-aged women. Method: This cross-sectional study analyzed data from the 2013 National Health…

Australia's regional innovation systems: inter-industry interaction in innovative activities in three Australian territories

PubMed Central

Schütz, Marlies H.

2017-01-01

ABSTRACT Regional specifics reveal in differences in economic activity and structure, the institutional, socio-economic and cultural environment and not least in the capability of regions to create new knowledge and to generate innovations. Focusing on the regional level, this paper for three Australian territories (New South Wales, Victoria and Queensland) explores patterns of innovative activities in their private business sectors. Furthermore, these patterns are compared to specifics of each region's economic structure. We make use of input–output-based innovation flow networks, which are directed and weighted instead of binary. The value added of the proposed analysis is that we are able to trace a variety of different aspects related to the structure of innovative activities for each territory. It gets evident that mostly innovative activities in each territory are not strong in ‘niche’ branches but in fields of intense economic activity, signalising the high path-dependency of innovative activities in a specific geographical environment. PMID:29097849

Australia's regional innovation systems: inter-industry interaction in innovative activities in three Australian territories.

PubMed

Schütz, Marlies H

2017-07-03

Regional specifics reveal in differences in economic activity and structure, the institutional, socio-economic and cultural environment and not least in the capability of regions to create new knowledge and to generate innovations. Focusing on the regional level, this paper for three Australian territories (New South Wales, Victoria and Queensland) explores patterns of innovative activities in their private business sectors. Furthermore, these patterns are compared to specifics of each region's economic structure. We make use of input-output-based innovation flow networks, which are directed and weighted instead of binary. The value added of the proposed analysis is that we are able to trace a variety of different aspects related to the structure of innovative activities for each territory. It gets evident that mostly innovative activities in each territory are not strong in 'niche' branches but in fields of intense economic activity, signalising the high path-dependency of innovative activities in a specific geographical environment.

Purification and substrate specificities of a fructanase from Kluyveromyces marxianus isolated from the fermentation process of Mezcal.

PubMed

Arrizon, Javier; Morel, Sandrine; Gschaedler, Anne; Monsan, Pierre

2011-02-01

A fructanase, produced by a Kluyveromyces marxianus strain isolated during the fermentation step of the elaboration process of "Mezcal de Guerrero" was purified and biochemically characterized. The active protein was a glycosylated dimer with a molecular weight of approximately 250 kDa. The specific enzymatic activity of the protein was determined for different substrates: sucrose, inulin, Agave tequilana fructan, levan and Actilight® and compared with the activity of Fructozyme®. The hydrolysis profile of the different substrates analyzed by HPAEC-PAD showed that the enzyme has different affinities over the substrates tested with a sucrose/inulin enzymatic activity ratio (S/I) of 125. For the hydrolysis of Agave tequilana fructans, the enzyme also showed a higher enzymatic activity and specificity than Fructozyme®, which is important for its potential application in the tequila industry. Copyright © 2010 Elsevier Ltd. All rights reserved.

Adapted shared reading at school for minimally verbal students with autism.

PubMed

Mucchetti, Charlotte A

2013-05-01

Almost nothing is known about the capacity of minimally verbal students with autism to develop literacy skills. Shared reading is a regular practice in early education settings and is widely thought to encourage language and literacy development. There is some evidence that children with severe disabilities can be engaged in adapted shared reading activities. The current study examines the impact of teacher-led adapted shared reading activities on engagement and story comprehension in minimally verbal 5-6-year-old children with autism using a multiple baseline/alternating treatment design. Four students and three teachers participated. Teachers conducted adapted shared reading activities with modified books (visual supports, three-dimensional objects, simplified text) and used specific strategies for increasing student engagement. Student performance during adapted activities was compared to performance during standard shared reading sessions. All four students showed increased story comprehension and engagement during adapted shared reading. Average percentage of session engaged was 87%-100% during adapted sessions, compared with 41%-52% during baseline. Average number of correct responses to story comprehension questions was 4.2-4.8 out of 6 during adapted sessions compared with 1.2-2 during baseline. Visual supports, tactile objects, and specific teaching strategies offer ways for minimally verbal students to meaningfully participate in literacy activities. Future research should investigate adapted shared reading activities implemented classroom-wide as well as joint engagement, language, and literacy outcomes after using such activities over time.

Strain-Specific Changes in Locomotor Behavior in Larval Zebrafish Elicited by Cholinergic Challenge

EPA Science Inventory

Some studies have compared the baseline behavior of different strains of larval zebrafish (Danio rerio), but there is sparse information on strain-specific responses to chemical challenges. The following study examines both the basal activity and response to a pharmacological cha...

Erythrocyte glucose-6-phosphate dehydrogenase from Brazilian opossum Didelphis marsupialis.

PubMed

Barretto, O C de O; Oshiro, M; Oliveira, R A G; Fedullo, J D L; Nonoyama, K

2006-05-01

In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD) of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 +/- 38 IU g-1 Hb-1 min-1 at 37 degrees C, compared to the human erythrocyte activity of 12 +/- 2 IU g-1 Hb-1 min-1 at 37 degrees C. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH) in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa). The Michaelis-Menten constants (Km: 55 microM) for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 microM) were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively). A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate.

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

PubMed

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

2016-02-01

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

Self-diagnosis of active head lice infestation by individuals from an impoverished community: high sensitivity and specificity.

PubMed

Pilger, Daniel; Khakban, Adak; Heukelbach, Jorg; Feldmeier, Hermann

2008-01-01

To compare sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-diagnosis for head lice infestation with visual inspection, we conducted a study in an urban slum in Brazil. Individuals were asked about active head lice infestation (self-diagnosis); we performed visual inspection and thereafter wet combing (gold standard). Of the 175 individuals included, 77 (44%) had an active head lice infestation. For self-diagnosis, sensitivity (80.5%), specificity (91.8%), PPV (88.6%) and NPV (85.7%) were high. Sensitivity of visual inspection was 35.1%. Public health professionals can use self-diagnosis as a diagnostic tool, to estimate accurately prevalence of pediculosis in a community, and to monitor ongoing intervention strategies.

An age-specific biokinetic model for iodine

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

Leggett, Richard Wayne

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

An age-specific biokinetic model for iodine

DOE PAGES

Leggett, Richard Wayne

2017-10-26

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

The CD63 basophil activation test in Hymenoptera venom allergy: a prospective study.

PubMed

Sturm, G J; Böhm, E; Trummer, M; Weiglhofer, I; Heinemann, A; Aberer, W

2004-10-01

The basophil activation test (BAT), which relies on flow cytometric quantitation of the allergen-induced up-regulation of the granule-associated marker CD63 in peripheral blood basophils, has been suggested to be a useful approach in detecting responsiveness to allergens. The purpose of this study was to establish the usefulness of the BAT with regard to the clinical history and current diagnostic tools in Hymenoptera venom allergy using a prospective study design. Fifty-seven consecutive patients allergic to Hymenoptera venom as defined by a systemic reaction after an insect sting, and 30 age- and sex-matched control subjects with a negative history were included. The degree and nature of sensitization was confirmed by skin testing, specific immunoglobulin E (IgE), serum tryptase levels and BAT. In the nonallergic control group only analysis of specific IgE and BAT were performed. Correlation of BAT, skin test and specific IgE, respectively, with the clinical history in the allergic group was termed as sensitivity and in the control group as specificity. Twenty one of 23 (91.3%) bee venom allergic patients and 29 of 34 (85.3%) patients allergic to wasp and hornet venom tested positive in BAT. The overall sensitivity of BAT, specific IgE and skin tests were 87.7, 91.2 and 93.0%, respectively. The overall specificities were 86.7% for BAT and 66.7% for specific IgE. No correlation between the severity of clinical symptoms and the magnitude of basophil activation was observed. The BAT seems to be an appropriate method to identify patients allergic to bee or wasp venom with a comparable sensitivity to standard diagnostic regimens. The higher specificity of BAT as compared with specific IgE makes this test a useful tool in the diagnosis of Hymenoptera venom allergy.

Seed specific expression and analysis of recombinant human adenosine deaminase (hADA) in three host plant species.

PubMed

Doshi, Ketan M; Loukanina, Natalia N; Polowick, Patricia L; Holbrook, Larry A

2016-10-01

The plant seed is a leading platform amongst plant-based storage systems for the production of recombinant proteins. In this study, we compared the activity of human adenosine deaminase (hADA) expressed in transgenic seeds of three different plant species: pea (Pisum sativum L.), Nicotiana benthamiana L. and tarwi (Lupinus mutabilis Sweet). All three species were transformed with the same expression vector containing the hADA gene driven by the seed-specific promoter LegA2 with an apoplast targeting pinII signal peptide. During the study, several independent transgenic lines were generated and screened from each plant species and only lines with a single copy of the gene of interest were used for hADA expression analysis. A stable transgenic canola line expressing the ADA protein, under the control of 35S constitutive promoter was used as both as a positive control and for comparative study with the seed specific promoter. Significant differences were detected in the expression of hADA. The highest activity of the hADA enzyme (Units/g seed) was reported in tarwi (4.26 U/g) followed by pea (3.23 U/g) and Nicotiana benthamiana (1.69 U/g). The expression of mouse ADA in canola was very low in both seed and leaf tissue compared to other host plants, confirming higher activity of seed specific promoter. Altogether, these results suggest that tarwi could be an excellent candidate for the production of valuable recombinant proteins.

Continuous directed evolution of aminoacyl-tRNA synthetases

PubMed Central

Bryson, David I.; Fan, Chenguang; Guo, Li-Tao; Miller, Corwin; Söll, Dieter; Liu, David R.

2017-01-01

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of non-canonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing non-canonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. PMID:29035361

Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review.

PubMed

Lardas, Michael; Liew, Matthew; van den Bergh, Roderick C; De Santis, Maria; Bellmunt, Joaquim; Van den Broeck, Thomas; Cornford, Philip; Cumberbatch, Marcus G; Fossati, Nicola; Gross, Tobias; Henry, Ann M; Bolla, Michel; Briers, Erik; Joniau, Steven; Lam, Thomas B; Mason, Malcolm D; Mottet, Nicolas; van der Poel, Henk G; Rouvière, Olivier; Schoots, Ivo G; Wiegel, Thomas; Willemse, Peter-Paul M; Yuan, Cathy Yuhong; Bourke, Liam

2017-12-01

Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain. To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer. MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken. Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr. This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in detail with patients during pretreatment counselling. Our review of the current evidence suggests that for a period of up to 6 yr after treatment, men with localised prostate cancer who were managed with active surveillance reported high levels of quality of life (QoL). Men treated with surgery reported mainly urinary and sexual problems, while those treated with external beam radiotherapy reported mainly bowel problems. Men eligible for brachytherapy reported urinary problems up to a year after therapy, but then their QoL returned gradually to as it was before treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Echicetin Coated Polystyrene Beads: A Novel Tool to Investigate GPIb-Specific Platelet Activation and Aggregation

PubMed Central

Petunin, Alexey; Clemetson, Kenneth J.; Gambaryan, Stepan; Walter, Ulrich

2014-01-01

von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways. PMID:24705415

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

PubMed

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-11-14

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

Exhausted Cytotoxic Control of Epstein-Barr Virus in Human Lupus

PubMed Central

Larsen, Martin; Sauce, Delphine; Deback, Claire; Arnaud, Laurent; Mathian, Alexis; Miyara, Makoto; Boutolleau, David; Parizot, Christophe; Dorgham, Karim; Papagno, Laura; Appay, Victor; Amoura, Zahir; Gorochov, Guy

2011-01-01

Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8+ T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8+ T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients. PMID:22028659

Exhausted cytotoxic control of Epstein-Barr virus in human lupus.

PubMed

Larsen, Martin; Sauce, Delphine; Deback, Claire; Arnaud, Laurent; Mathian, Alexis; Miyara, Makoto; Boutolleau, David; Parizot, Christophe; Dorgham, Karim; Papagno, Laura; Appay, Victor; Amoura, Zahir; Gorochov, Guy

2011-10-01

Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8+ T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8+ T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients.

Asymmetry of neck motion and activation of the cervical paraspinal muscles during prone neck extension in subjects with unilateral posterior neck pain.

PubMed

Park, Kyue-Nam; Kwon, Oh-Yun; Kim, Su-Jung; Kim, Si-Hyun

2017-01-01

Although unilateral posterior neck pain (UPNP) is more prevalent than central neck pain, little is known about how UPNP affects neck motion and the muscle activation pattern during prone neck extension. To investigate whether deviation in neck motion and asymmetry of activation of the bilateral cervical paraspinal muscles occur during prone neck extension in subjects with UPNP compared to subjects without UPNP. This study recruited 20 subjects with UPNP and 20 age- and sex-matched control subjects without such pain. Neck motion and muscle onset time during prone neck extension were measured using a three-dimensional motion-analysis system and surface electromyography. The deviation during prone neck extension was greater in the UPNP group than in the controls (p < 0.05). Compared with the controls, cervical extensor muscle activation in the UPNP group was significantly delayed on the painful side during prone neck extension (p < 0.05). Subjects with UPNP showed greater asymmetry of neck motion and muscle activation during prone neck extension compared with the controls. This suggests that UPNP has specific effects on neck motion asymmetry and the functions of the cervical extensors, triggering a need for specific evaluation and exercises in the management of patients with UPNP.

Different cultivation methods to acclimatise ammonia-tolerant methanogenic consortia.

PubMed

Tian, Hailin; Fotidis, Ioannis A; Mancini, Enrico; Angelidaki, Irini

2017-05-01

Bioaugmentation with ammonia tolerant-methanogenic consortia was proposed as a solution to overcome ammonia inhibition during anaerobic digestion process recently. However, appropriate technology to generate ammonia tolerant methanogenic consortia is still lacking. In this study, three basic reactors (i.e. batch, fed-batch and continuous stirred-tank reactors (CSTR)) operated at mesophilic (37°C) and thermophilic (55°C) conditions were assessed, based on methane production efficiency, incubation time, TAN/FAN (total ammonium nitrogen/free ammonia nitrogen) levels and maximum methanogenic activity. Overall, fed-batch cultivation was clearly the most efficient method compared to batch and CSTR. Specifically, by saving incubation time up to 150%, fed-batch reactors were acclimatised to nearly 2-fold higher FAN levels with a 37%-153% methanogenic activity improvement, compared to batch method. Meanwhile, CSTR reactors were inhibited at lower ammonia levels. Finally, specific methanogenic activity test showed that hydrogenotrophic methanogens were more active than aceticlastic methanogens in all FAN levels above 540mgNH 3 -NL -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Physical Activities and Sedentary Pursuits in African American and Caucasian Girls

ERIC Educational Resources Information Center

Dowda, Marsha; Pate, Russell R.; Felton, Gwen M.; Saunders, Ruth; Ward, Dianne S.; Dishman, Rod K.; Trost, Stewart G.

2004-01-01

The purposes of this study were to describe and compare the specific physical activity choices and sedentary pursuits of African American and Caucasian American girls. Participants were 1,124 African American and 1,068 Caucasian American eighth-grade students from 31 middle schools. The 3-Day Physical Activity Recall (3DPAR) was used to measure…

Secondary Market Activities of the Student Loan Marketing Association. Report to the Committee on Labor and Human Resources, United States Senate.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC.

Lending and secondary market activities of the Student Loan Marketing Association (Sallie Mae) since it began operations in 1973 were reviewed. Specific areas of review were: the Association's legislative development and financial activities, its profitability compared to commercial banks and other government-sponsored enterprises that provide…

The structure of walking activity in people after stroke compared with older adults without disability: a cross-sectional study.

PubMed

Roos, Margaret A; Rudolph, Katherine S; Reisman, Darcy S

2012-09-01

People with stroke have reduced walking activity. It is not known whether this deficit is due to a reduction in all aspects of walking activity or only in specific areas. Understanding specific walking activity deficits is necessary for the development of interventions that maximize improvements in activity after stroke. The purpose of this study was to examine walking activity in people poststroke compared with older adults without disability. A cross-sectional study was conducted. Fifty-four participants poststroke and 18 older adults without disability wore a step activity monitor for 3 days. The descriptors of walking activity calculated included steps per day (SPD), bouts per day (BPD), steps per bout (SPB), total time walking per day (TTW), percentage of time walking per day (PTW), and frequency of short, medium, and long walking bouts. Individuals classified as household and limited community ambulators (n=29) did not differ on any measure and were grouped (HHA-LCA group) for comparison with unlimited community ambulators (UCA group) (n=22) and with older adults without disability (n=14). The SPD, TTW, PTW, and BPD measurements were greatest in older adults and lowest in the HHA-LCA group. Seventy-two percent to 74% of all walking bouts were short, and this finding did not differ across groups. Walking in all categories (short, medium, and long) was lowest in the HHA-LCA group, greater in the UCA group, and greatest in older adults without disability. Three days of walking activity were captured. The specific descriptors of walking activity presented provide insight into walking deficits after stroke that cannot be ascertained by looking at steps per day alone. The deficits that were revealed could be addressed through appropriate exercise prescription, underscoring the need to analyze the structure of walking activity.

The disruption of two salt bridges of the cold-active xylanase XynGR40 results in an increase in activity, but a decrease in thermostability.

PubMed

Wang, Guozeng; Wu, Jingjing; Lin, Juan; Ye, Xiuyun; Yao, Bin

2016-12-02

Cold-active xylanases are of great interest due to their large potential for application in the food industry. In this study, salt bridges of the eight glycoside hydrolase (GH) family 10 cold-active xylanases reported to date were predicted and the salt bridges specific to the cold-active xylanase XynGR40 were identified. Seven mutants were constructed to disrupt salt bridges specific to XynGR40. The results suggested that five mutants lost their xylanase activity, while the other two mutants, D30N and D83N, displayed different properties when compared with the wild-type XynGR40. First, both mutations showed an obvious decrease in thermostability, with the T 1/2 of D30N and D83N at 50 °C being about one half and one sixth of the wild-type, respectively. Second, both D30N and D83N had a higher specific activity than the wild-type, with activities about 13 and 163% higher, respectively. Third, both D30N and D83N had high k cat and K m values, which resulted in a higher catalytic efficiency of the mutant D83N, but a lower catalytic efficiency of the mutant D30N compared to the wild-type. Our results suggested that salt bridges play important roles in both the activity and thermostability of the cold-active xylanase XynGR40. The mutant D83N had a higher k cat and higher relative activity at low temperatures than the wild-type, and is a good candidate for application in the food industry. Copyright © 2016 Elsevier Inc. All rights reserved.

Muscle-strengthening and aerobic activities and mortality among 3+ year cancer survivors in the U.S.

PubMed

Tarasenko, Yelena N; Linder, Daniel F; Miller, Eric A

2018-05-01

This study examined the association between adherence to American College of Sports Medicine and American Cancer Society guidelines on aerobic and muscle-strengthening activities and mortality risks among 3+ year cancer survivors in the U.S. The observational study was based on 1999-2009 National Health Interview Survey Linked Mortality Files with follow-up through 2011. After applying exclusion criteria, there were 13,997 observations. The hazard ratios (HRs) for meeting recommendations on muscle-strengthening activities only, on aerobic activities only, and on both types of physical activity (i.e., adhering to complete guidelines) were calculated using a reference group of cancer survivors engaging in neither. Unadjusted and adjusted HRs of all-cause, cancer-specific, and cardiovascular disease-specific mortalities were estimated using Cox proportional hazards models. In all models, compared to the reference group, cancer survivors adhering to complete guidelines had significantly decreased all-cause, cancer-specific, and cardiovascular disease-specific mortalities (HRs ranged from 0.37 to 0.64, p's < 0.05). There were no statistically significant differences between hazard rates of cancer survivors engaging in recommended levels of muscle-strengthening activities only and the reference group (HRs ranged from 0.76 to 0.94, p's > 0.05). Wald test statistics suggested a significant dose-response relationship between levels of adherence to complete guidelines and cancer-specific mortality. While muscle-strengthening activities by themselves do not appear to reduce mortality risks, such activities may provide added cancer-specific survival benefits to 3+ year cancer survivors who are already aerobically active.

Active member control of a precision structure with an H(infinity) performance objective

NASA Technical Reports Server (NTRS)

Fanson, J. L.; Chu, C.-C.; Smith, R. S.; Anderson, E. H.

1990-01-01

This paper addresses the noncollocated control of active structures using active structural elements. A top level architecture for active structures is presented, and issues pertaining to robust control of structures are discussed. Controllers optimized for an H sub inf performance specification are implemented on a test structure and the results are compared with analytical predictions. Directions for further research are identified.

Modeling energy consumption in membrane bioreactors for wastewater treatment in north Africa.

PubMed

Skouterisl, George; Arnot, Tom C; Jraou, Mouna; Feki, Firas; Sayadi, Sami

2014-03-01

Two pilot-scale membrane bioreactors were operated alongside a full-sized activated sludge plant in Tunisia in order to compare specific energy demand and treated water quality. Energy consumption rates were measured for the complete membrane bioreactor systems and for their different components. Specific energy demand was measured for the systems and compared with the activated sludge plant, which operated at around 3 kWh m(-3). A model was developed for each membrane bioreactor based on both dynamic and steady-state mass balances, microbial kinetics and stoichiometry, and energy balance. Energy consumption was evaluated as a function of mixed-liquor suspended solids concentration, net permeate fluxes, and the resultant treated water quality. This work demonstrates the potential for using membrane bioreactors in decentralised domestic water treatment in North Africa, at energy consumption levels similar or lower than conventional activated sludge systems, with the added benefit of producing treated water suitable for unrestricted crop irrigation.

Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury

PubMed Central

Barone, Sharon L.; Xu, Jie; Steinbergs, Nora; Schuster, Rebecca; Lentsch, Alex B.; Amlal, Hassane; Wang, Jiang; Casero, Robert A.; Soleimani, Manoocher

2012-01-01

Activation of spermine/spermidine-N1-acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl4). The expression and activity of SSAT increase in the liver subsequent to CCl4 administration. Furthermore, the early liver injury after CCl4 treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl4. Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl4-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration. PMID:22723264

Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury.

PubMed

Zahedi, Kamyar; Barone, Sharon L; Xu, Jie; Steinbergs, Nora; Schuster, Rebecca; Lentsch, Alex B; Amlal, Hassane; Wang, Jiang; Casero, Robert A; Soleimani, Manoocher

2012-09-01

Activation of spermine/spermidine-N(1)-acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl(4)). The expression and activity of SSAT increase in the liver subsequent to CCl(4) administration. Furthermore, the early liver injury after CCl(4) treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl(4). Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl(4)-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration.

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.

A Two-Generation Study of Body Mass Index, Energy Balance and Specific Physical Activity of College Students and Their Respective Parents Living in the Same Household at Los Angeles, California, U.S.A.

ERIC Educational Resources Information Center

Liang, Ying; Lee, Judy; Tam, Chick F.; Bridges, Elizabeth; Keating, Xiaofen D.

2007-01-01

The purpose was to compare the differences in body mass index (BMI), energy balance (EB) and specific physical activity (SPA) between 30 CSULA college students (Y) and their respective parents (O) living in the same household at Los Angeles, California, U.S.A. Each student completed a 24-hour dietary record with SPA journal, and the same for…

Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells

PubMed Central

Cirelli, Kimberly M.; Dan, Jennifer M.; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane

2017-01-01

The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells. PMID:29065175

Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells.

PubMed

Reiss, Samantha; Baxter, Amy E; Cirelli, Kimberly M; Dan, Jennifer M; Morou, Antigoni; Daigneault, Audrey; Brassard, Nathalie; Silvestri, Guido; Routy, Jean-Pierre; Havenar-Daughton, Colin; Crotty, Shane; Kaufmann, Daniel E

2017-01-01

The identification and study of antigen-specific CD4 T cells, both in peripheral blood and in tissues, is key for a broad range of immunological research, including vaccine responses and infectious diseases. Detection of these cells is hampered by both their rarity and their heterogeneity, in particular with regards to cytokine secretion profiles. These factors prevent the identification of the total pool of antigen-specific CD4 T cells by classical methods. We have developed assays for the highly sensitive detection of such cells by measuring the upregulation of surface activation induced markers (AIM). Here, we compare two such assays based on concurrent expression of CD69 plus CD40L (CD154) or expression of OX40 plus CD25, and we develop additional AIM assays based on OX40 plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for detection of vaccine and natural infection-induced CD4 T cell responses and show that these assays identify distinct, but overlapping populations of antigen-specific CD4 T cells, a subpopulation of which can also be detected on the basis of cytokine synthesis. Bystander activation had minimal effect on AIM markers. However, some T regulatory cells upregulate CD25 upon antigen stimulation. We therefore validated AIM assays designed to exclude most T regulatory cells, for both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through head-to-head comparisons and methodological improvements, we show that AIM assays represent a sensitive and valuable method for the detection of antigen-specific CD4 T cells.

Structures of Human DPP7 Reveal the Molecular Basis of Specific Inhibition and the Architectural Diversity of Proline-Specific Peptidases

PubMed Central

Dong, Aiping; Seitova, Almagul; Crombett, Lissete; Shewchuk, Lisa M.; Hassell, Annie M.; Sweitzer, Sharon M.; Sweitzer, Thomas D.; McDevitt, Patrick J.; Johanson, Kyung O.; Kennedy-Wilson, Karen M.; Cossar, Doug; Bochkarev, Alexey; Gruber, Karl; Dhe-Paganon, Sirano

2012-01-01

Proline-specific dipeptidyl peptidases (DPPs) are emerging targets for drug development. DPP4 inhibitors are approved in many countries, and other dipeptidyl peptidases are often referred to as DPP4 activity- and/or structure-homologues (DASH). Members of the DASH family have overlapping substrate specificities, and, even though they share low sequence identity, therapeutic or clinical cross-reactivity is a concern. Here, we report the structure of human DPP7 and its complex with a selective inhibitor Dab-Pip (L-2,4-diaminobutyryl-piperidinamide) and compare it with that of DPP4. Both enzymes share a common catalytic domain (α/β-hydrolase). The catalytic pocket is located in the interior of DPP7, deep inside the cleft between the two domains. Substrates might access the active site via a narrow tunnel. The DPP7 catalytic triad is completely conserved and comprises Ser162, Asp418 and His443 (corresponding to Ser630, Asp708 and His740 in DPP4), while other residues lining the catalytic pockets differ considerably. The “specificity domains” are structurally also completely different exhibiting a β-propeller fold in DPP4 compared to a rare, completely helical fold in DPP7. Comparing the structures of DPP7 and DPP4 allows the design of specific inhibitors and thus the development of less cross-reactive drugs. Furthermore, the reported DPP7 structures shed some light onto the evolutionary relationship of prolyl-specific peptidases through the analysis of the architectural organization of their domains. PMID:22952628

A new potential spreading factor: Streptomyces koganeiensis hyaluronidase. A comparative study with bovine testes hyaluronidase and recombinant human hyaluronidase of the HA degradation in ECM.

PubMed

Pavan, Mauro; Beninatto, Riccardo; Galesso, Devis; Panfilo, Susi; Vaccaro, Susanna; Messina, Luciano; Guarise, Cristian

2016-04-01

Recombinant human hyaluronidase has been used in the interstitial matrix to promote the dispersion of therapeutics. The production and isolation of an extracellular hyaluronidase from Streptomyces koganeiensis (rHyal_Sk) has recently been described. The specificity of rHyal_Sk has been assessed against heparan sulfate, chondroitin sulfates and sulfated HAs. The oligomers generated by HA degradation have been investigated by MALDI-TOF MS analysis. rHyal_Sk has been compared with BTH and PH20 in vitro, against cross-linked HA (ACP) and HA-aggrecan complex, and in vivo, by means of a diffusion assay in nude mice. Depolymerization of HA by rHyal_Sk gave tetra-, hexa- and octasaccharides in high yields. The reaction mechanism and the high HA specificity were demonstrated. The in vivo diffusion assay, supported by the in vitro tests, evidenced an initially enhanced enzymatic activity of rHyal_Sk compared to BTH and PH20. rHyal_Sk, compared to BTH and PH20, showed higher substrate specificity and no inhibition from GAGs sulfate, together with a superior performance for HA depolymerization in ECM. As better predictive tests for the in vivo activity of hyaluronidase we developed two assays based on the degradation of ACP or of the HA-aggrecan complex. rHyal_Sk is a new potential spreading factor for intradermal drug administration. Hyaluronidases of distinct classes, that show equivalent activities in a common turbidimetric assay, could have different potencies and dose-efficacies in vivo which influences the therapeutic effect. The new proposed in vitro tests are designed to obtain a predictive characterization of the enzyme activity in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional Assessment of Region-Specific Neglect: Are There Differential Behavioural Consequences of Peripersonal versus Extrapersonal Neglect?

PubMed Central

Nijboer, T. C. W.; ten Brink, A. F.; Kouwenhoven, M.; Visser-Meily, J. M. A.

2014-01-01

Background. Region-specific types of neglect (peripersonal and extrapersonal) have been dissociated, yet, differential behavioural consequences are unknown. Objective. The aim of the current study was to investigate behavioural consequences at the level of basic activities of daily living of region-specific neglect, using the Catherine Bergego Scale (CBS). Methods. 118 stroke patients were screened within the first two weeks after admission to the rehabilitation center for inpatient rehabilitation. Results. Patients with peripersonal neglect and patients with neglect for both regions had significantly higher total score on the CBS compared to nonneglect patients. Total scores for patients with extrapersonal neglect were comparable to non-neglect patients. ADL impairments were found across activities (e.g., looking towards one side, forgetting body parts, colliding) for both patients with peripersonal neglect and patients with neglect for both regions. Patients with extrapersonal neglect were only impaired on the item on way finding. Conclusions. When diagnosing neglect, it is relevant to distinguish the type of region-specific neglect and, where needed, to adjust the rehabilitation program accordingly. As the CBS is not developed to typically measure ADL in extrapersonal neglect, it would be of importance to add other (instrumental) activities that heavily rely on processing information in farther space. PMID:24825959

The Attributable Proportion of Specific Leisure-Time Physical Activities to Total Leisure Activity Volume Among US Adults, National Health and Nutrition Examination Survey 1999-2006.

PubMed

Watson, Kathleen Bachtel; Dai, Shifan; Paul, Prabasaj; Carlson, Susan A; Carroll, Dianna D; Fulton, Janet

2016-11-01

Previous studies have examined participation in specific leisure-time physical activities (PA) among US adults. The purpose of this study was to identify specific activities that contribute substantially to total volume of leisure-time PA in US adults. Proportion of total volume of leisure-time PA moderate-equivalent minutes attributable to 9 specific types of activities was estimated using self-reported data from 21,685 adult participants (≥ 18 years) in the National Health and Nutrition Examination Survey 1999-2006. Overall, walking (28%), sports (22%), and dancing (9%) contributed most to PA volume. Attributable proportion was higher among men than women for sports (30% vs. 11%) and higher among women than men for walking (36% vs. 23%), dancing (16% vs. 4%), and conditioning exercises (10% vs. 5%). The proportion was lower for walking, but higher for sports, among active adults than those insufficiently active and increased with age for walking. Compared with other racial/ethnic groups, the proportion was lower for sports among non-Hispanic white men and for dancing among non-Hispanic white women. Walking, sports, and dance account for the most activity time among US adults overall, yet some demographic variations exist. Strategies for PA promotion should be tailored to differences across population subgroups.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

PubMed Central

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo

2011-01-01

Background 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. Methods 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. Results 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. Conclusion 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. PMID:21738897

Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus Protease

PubMed Central

Lin, Ying-Chuan; Beck, Zachary; Lee, Taekyu; Le, Van-Duc; Morris, Garrett M.; Olson, Arthur J.; Wong, Chi-Huey; Elder, John H.

2000-01-01

Feline immunodeficiency virus (FIV) protease is structurally very similar to human immunodeficiency virus (HIV) protease but exhibits distinct substrate and inhibitor specificities. We performed mutagenesis of subsite residues of FIV protease in order to define interactions that dictate this specificity. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. FIV proteases all failed to cut HIV-1 matrix/capsid, P1/P6, P6/protease, and protease/reverse transcriptase junctions, indicating that none of the substitutions were sufficient to change the specificity completely. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. The data also suggest that FIV protease prefers a hydrophobic P2/P2′ residue like Val over Asn or Glu, which are utilized by HIV-1 protease, and that S2/S2′ might play a critical role in distinguishing FIV and HIV-1 protease by specificity. The findings extend our observations regarding the interactions involved in substrate binding and aid in the development of broad-based inhibitors. PMID:10775609

Characterization and organic electric-double-layer-capacitor application of KOH activated coal-tar-pitch-based carbons: Effect of carbonization temperature

NASA Astrophysics Data System (ADS)

Choi, Poo Reum; Lee, Eunji; Kwon, Soon Hyung; Jung, Ji Chul; Kim, Myung-Soo

2015-12-01

The present study reports the influence of pre-carbonization on the properties of KOH-activated coal tar pitch (CTP). The change of crystallinity and pore structure of pre-carbonized CTPs as well as their activated carbons (ACs) as function of pre-carbonization temperature are investigated. The crystallinity of pre-carbonized CTPs increases with increasing the carbonization temperature up to 600 °C, but a disorder occurs during the carbonization around 700 °C and an order happens gradually with increasing the carbonization temperatures in range of 800-1000 °C. The CTPs pre-carbonized at high temperatures are more difficult to be activated with KOH than those pre-carbonized at low temperatures due to the increase of micro-crystalline size and the decrease of surface functional groups. The micro-pores and meso-pores are well developed at around 1.0 nm and 2.4 nm, respectively, as the ACs are pre-carbonized at temperatures of 500-600 °C, exhibiting high specific capacitances as electrode materials for electric double layer capacitor (EDLC). Although the specific surface area (SSA) and pore volume of ACs pre-carbonized at temperatures of 900-1000 °C are extraordinary low (non-porous) as compared to those of AC pre-carbonized at 600 °C, their specific capacitances are comparable to each other. The large specific capacitances with low SSA ACs can be attributed to the structural change resulting from the electrochemical activation during the 1st charge above 2.0 V.

Comparison of Activity Profiles and Physiological Demands Between International Rugby Sevens Matches and Training.

PubMed

Higham, Dean G; Pyne, David B; Anson, Judith M; Hopkins, Will G; Eddy, Anthony

2016-05-01

The specificity of contemporary training practices of international rugby sevens players is unknown. We quantified the positional group-specific activity profiles and physiological demands of on-field training activities and compared these with match demands. Twenty-two international matches and 63 rugby-specific training drills were monitored in 25 backs and 17 forwards from a national squad of male rugby sevens players over a 21-month period. Drills were classified into 3 categories: low-intensity skill refining (n = 23 drills, 560 observations), moderate- to high-intensity skill refining (n = 28 drills, 600 observations), and game simulation (n = 12 drills, 365 observations). Movement patterns (via Global Positioning System devices) and physiological load (via heart rate monitors) were recorded for all activities, and the differences between training and matches were quantified using magnitude-based inferential statistics. Distance covered in total and at ≥3.5 m·s, maximal velocity, and frequency of accelerations and decelerations were lower for forwards during competition compared with those for backs by a small but practically important magnitude. No clear positional group differences were observed for physiological load during matches. Training demands exceeded match demands only for frequency of decelerations of forwards during moderate- to high-intensity skill-refining drills and only by a small amount. Accelerations and distance covered at ≥6 m·s were closer to match values for forwards than for backs during all training activities, but training drills consistently fell below the demands of international competition. Coaches could therefore improve physical and physiological specificity by increasing the movement demands and intensity of training drills.

Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

PubMed Central

Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

2011-01-01

Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis.

PubMed

Grayson, Peter C; Alehashemi, Sara; Bagheri, Armin A; Civelek, Ali Cahid; Cupps, Thomas R; Kaplan, Mariana J; Malayeri, Ashkan A; Merkel, Peter A; Novakovich, Elaine; Bluemke, David A; Ahlman, Mark A

2018-03-01

To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months. FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse. © 2017, American College of Rheumatology.

Autobiographical memory: a candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment

PubMed Central

McCrory, Eamon J.; Puetz, Vanessa B.; Maguire, Eleanor A.; Mechelli, Andrea; Palmer, Amy; Gerin, Mattia I.; Kelly, Philip A.; Koutoufa, Iakovina; Viding, Essi

2017-01-01

Background Altered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and post-traumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk. Aims To investigate the impact of childhood maltreatment on ABM functioning. Method Thirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging. Results Children with maltreatment experience showed reduced hippocampal and increased middle temporal and parahippocampal activation during positive ABM recall compared with peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network. Conclusions Childhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and post-traumatic stress disorder. PMID:28882830

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.

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

Unterberger, Claudia; Hanson, Steven; Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN

Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 tomore » be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity.« less

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed

Baselski, V S; Medina, R A; Parker, C D

1978-11-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed Central

Baselski, V S; Medina, R A; Parker, C D

1978-01-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12. PMID:730364

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

DOE PAGES

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah; ...

2017-04-11

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

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

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Development of a Checklist of Inservice Activities for Primary and Secondary Teachers in Australian Schools. C.A.T. Education Monograph No. 8.

ERIC Educational Resources Information Center

Meyer, Rex

Literature on the goals, barriers, and trends in inservice education is reviewed here, and criteria for development of an inservice program as well as a checklist of possible activities are provided. Specific activities outlined are: courses; workshops; conferences; exchanges and secondments; comparative educational tours; study leave and study…

Comparing Supply-Side Specifications in Models of Global Agriculture and the Food System

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

Robinson, Sherman; van Meijl, Hans; Willenbockel, Dirk

This paper compares the theoretical specification of production and technical change across the partial equilibrium (PE) and computable general equilibrium (CGE) models of the global agricultural and food system included in the AgMIP model comparison study. The two modeling approaches have different theoretical underpinnings concerning the scope of economic activity they capture and how they represent technology and the behavior of supply and demand in markets. This paper focuses on their different specifications of technology and supply behavior, comparing their theoretical and empirical treatments. While the models differ widely in their specifications of technology, both within and between the PEmore » and CGE classes of models, we find that the theoretical responsiveness of supply to changes in prices can be similar, depending on parameter choices that define the behavior of supply functions over the domain of applicability defined by the common scenarios used in the AgMIP comparisons. In particular, we compare the theoretical specification of supply in CGE models with neoclassical production functions and PE models that focus on land and crop yields in agriculture. In practice, however, comparability of results given parameter choices is an empirical question, and the models differ in their sensitivity to variations in specification. To illustrate the issues, sensitivity analysis is done with one global CGE model, MAGNET, to indicate how the results vary with different specification of technical change, and how they compare with the results from PE models.« less

When a Step Is Not a Step! Specificity Analysis of Five Physical Activity Monitors.

PubMed

O'Connell, Sandra; ÓLaighin, Gearóid; Quinlan, Leo R

2017-01-01

Physical activity is an essential aspect of a healthy lifestyle for both physical and mental health states. As step count is one of the most utilized measures for quantifying physical activity it is important that activity-monitoring devices be both sensitive and specific in recording actual steps taken and disregard non-stepping body movements. The objective of this study was to assess the specificity of five activity monitors during a variety of prescribed non-stepping activities. Participants wore five activity monitors simultaneously for a variety of prescribed activities including deskwork, taking an elevator, taking a bus journey, automobile driving, washing and drying dishes; functional reaching task; indoor cycling; outdoor cycling; and indoor rowing. Each task was carried out for either a specific duration of time or over a specific distance. Activity monitors tested were the ActivPAL micro™, NL-2000™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2)™, Fitbit One™ and Jawbone UP™. Participants were video-recorded while carrying out the prescribed activities and the false positive step count registered on each activity monitor was obtained and compared to the video. All activity monitors registered a significant number of false positive steps per minute during one or more of the prescribed activities. The Withings™ activity performed best, registering a significant number of false positive steps per minute during the outdoor cycling activity only (P = 0.025). The Jawbone™ registered a significant number of false positive steps during the functional reaching task and while washing and drying dishes, which involved arm and hand movement (P < 0.01 for both). The ActivPAL™ registered a significant number of false positive steps during the cycling exercises (P < 0.001 for both). As a number of false positive steps were registered on the activity monitors during the non-stepping activities, the authors conclude that non-stepping physical activities can result in the false detection of steps. This can negatively affect the quantification of physical activity with regard to step count as an output. The Withings™ activity monitor performed best with regard to specificity during the activities of daily living tested.

Active and Collaborative Learning in an Introductory Electrical and Computer Engineering Course

ERIC Educational Resources Information Center

Kotru, Sushma; Burkett, Susan L.; Jackson, David Jeff

2010-01-01

Active and collaborative learning instruments were introduced into an introductory electrical and computer engineering course. These instruments were designed to assess specific learning objectives and program outcomes. Results show that students developed an understanding comparable to that of more advanced students assessed later in the…

Jaw and Order

ERIC Educational Resources Information Center

Mooshammer, Christine; Hoole, Philip; Geumann, Anja

2007-01-01

It is well-accepted that the jaw plays an active role in influencing vowel height. The general aim of the current study is to further investigate the extent to which the jaw is active in producing consonantal distinctions, with specific focus on coronal consonants. Therefore, tongue tip and jaw positions are compared for the German coronal…

Reduced response to Epstein–Barr virus antigens by T-cells in systemic lupus erythematosus patients

PubMed Central

Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie; Mortensen, Shila; Larsen, Janni Lisander; Houen, Gunnar; Duus, Karen

2014-01-01

Objective Epstein–Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. Methods T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay. Results SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients. Conclusions These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed. PMID:25396062

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

Hours spent and energy expended in physical activity domains: Results from The Tomorrow Project cohort in Alberta, Canada

PubMed Central

2011-01-01

Background Knowledge of adult activity patterns across domains of physical activity is essential for the planning of population-based strategies that will increase overall energy expenditure and reduce the risk of obesity and related chronic diseases. We describe domain-specific hours of activity and energy expended among participants in a prospective cohort in Alberta, Canada. Methods The Past Year Total Physical Activity Questionnaire was completed by 15,591 Tomorrow Project® participants, between 2001 and 2005 detailing physical activity type, duration, frequency and intensity. Domain-specific hours of activity and activity-related energy expenditure, expressed as a percent of total energy expenditure (TEE) (Mean (SD); Median (IQR)) are reported across inactive (<1.4), low active (1.4 to 1.59), active (1.6 to 1.89) and very active (≥ 1.9) Physical Activity Level (PAL = TEE:REE) categories. Results In very active women and amongst all men except those classified as inactive, activity-related energy expenditure comprised primarily occupational activity. Amongst inactive men and women in active, low active and inactive groups, activity-related energy expenditure from household activity was comparable to, or exceeded that for occupational activity. Leisure-time activity-related energy expenditure decreased with decreasing PAL categories; however, even amongst the most active men and women it accounted for less than 10 percent of TEE. When stratified by employment status, leisure-time activity-related energy expenditure was greatest for retired men [mean (SD): 10.8 (8.5) percent of TEE], compared with those who were fully employed, employed part-time or not employed. Transportation-related activity was negligible across all categories of PAL and employment status. Conclusion For the inactive portion of this population, active non-leisure activities, specifically in the transportation and occupational domains, need to be considered for inclusion in daily routines as a means of increasing population-wide activity levels. Environmental and policy changes to promote active transport and workplace initiatives could increase overall daily energy expenditure through reducing prolonged sitting time. PMID:21985559

Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

PubMed Central

Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

2017-01-01

Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

An atlas of active enhancers across human cell types and tissues

NASA Astrophysics Data System (ADS)

Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Consortium, The Fantom; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin

2014-03-01

Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

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.

Activation of the Nrf2-ARE Pathway in Hepatocytes Protects Against Steatosis in Nutritionally Induced Non-alcoholic Steatohepatitis in Mice

PubMed Central

Lee, Lung-Yi; Köhler, Ulrike A.; Zhang, Li; Roenneburg, Drew; Werner, Sabine; Johnson, Jeffrey A.; Foley, David P.

2014-01-01

Oxidative stress is implicated in the development of non-alcoholic steatohepatitis (NASH). The Nrf2-antioxidant response element pathway protects cells from oxidative stress. Studies have shown that global Nrf2 deficiency hastens the progression of NASH. The purpose of this study was to determine whether long-term hepatocyte-specific activation of Nrf2 mitigates NASH progression. Transgenic mice expressing a constitutively active Nrf2 construct in hepatocytes (AlbCre+/caNrf2+) and littermate controls were generated. These mice were fed standard or methionine-choline-deficient (MCD) diet, a diet used to induce NASH development in rodents. After 28 days of MCD dietary feeding, mice developed significant increases in steatosis, inflammation, oxidative stress, and HSC activation compared with those mice on standard diet. AlbCre+/caNrf2+ animals had significantly decreased serum transaminases and reduced steatosis when compared with the AlbCre+/caNrf2− animals. This significant reduction in steatosis was associated with increased expression of genes involved in triglyceride export (MTTP) and β-oxidation (CPT2). However, there were no differences in the increased oxidative stress, inflammation, and HSC activation from MCD diet administration between the AlbCre+/caNrf2− and AlbCre+/caNrf2+ animals. We conclude that hepatocyte-specific activation of Nrf2-mediated gene expression decreased hepatocellular damage and steatosis in a dietary model of NASH. However, hepatocyte-specific induction of Nrf2-mediated gene expression alone is insufficient to mitigate inflammation, oxidative stress, and HSC activation in this nutritional NASH model. PMID:25294219

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

PubMed

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-09-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

Effect of specific activity on neuroblastoma uptake of I-123-meta-iodobenzylguanidine in nude mice xenografted with SK-N-SH cells.

PubMed

Farahati, J; Coenen, H; Dutschka, K; Stuben, G; Knuhmann, K; Budach, W; Kremens, B; Reiners, C

1997-01-01

The effect of specific activity of meta[I-123]iodobenzylguanidine ([I-123]MIBG) on neuroblastoma uptake was studied in a nude mouse model (NMRI nu/nu) xenografted subcutaneously with SK-N-SH cells. Groups of eight animals received [I-123]MIBG intravenously with a specific activity of greater than or equal to 260 GBq/mu mol (no-carrier-added), 3.7 GBq/mu mol, 37 MBq/mu mol, and 0.37 MBq/mu mol, respectively. All animals in the group injected with 0.37 MBq/mu mol died immediately after the injection. Al 4 and 24 h, there was no significant effect of specific activity on tumor uptake of [I-123]MIBG in the different groups. The uptake of non-tumor tissue was in general lower with 37 MBq/mu mol compared to higher specific activities. The differences in blood, heart, liver, spleen and lungs were statistically significant at 24 h, whereas at 4 h significant differences were only present in the heart, liver and lungs. The results suggest that for the treatment of children with neuroblastoma a lower specific activity of radioiodinated MIBG may minimize the radiation exposure to non-tumor tissue but not to the tumor. Higher mass of MIBG >0.5 mu mol/g, however, is considered as lethal dose in our nude mice model and corresponding doses may cause toxic side effects in human.

Frequency distribution of specific activities and radiological hazard assessment in surface beach sand samples collected in Bangsaen beach in Chonburi province, Thailand

NASA Astrophysics Data System (ADS)

Changkit, N.; Boonkrongcheep, R.; Youngchauy, U.; Polthum, S.; Kessaratikoon, P.

2017-09-01

The specific activities of natural radionuclides (40K, 226Ra and 232Th) in 50 surface beach sand samples collected from Bangsaen beach in Chonburi province in the easthern region of Thailand, were measured and evaluated. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system in the special laboratory at Thailand Institute of Nuclear Technology (Public Organization). The IAEA-SOIL-375 reference material was used to analyze the concentration of 40K, 226Ra and 232Th in all samples. It was found that the specific activities of 40K, 226Ra and 232Th were ranged from 510.85 - 771.35, 8.17 - 17.06 and 4.25 - 15.68 Bq/kg. Furthermore, frequency distribution of the specific activities were studied, analyzed and found to be the asymmetrical distribution by using a statistical computer program. Moreover, four radiological hazard indices for the investigated area were also calculated by using the median values of specific activities of 40K, 226Ra and 232Th. The results were also compared with the Office of Atoms for Peace (OAP) annual report data, Thailand and global radioactivity measurement and evaluations.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

PubMed

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

PubMed Central

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

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.

Coho salmon Oncorhynchus kisutch strain differences in disease resistance and non-specific immunity, following immersion challenges with Vibrio anguillarum

USGS Publications Warehouse

Balfry, Shannon K.; Maule, Alec G.; Iwama, George K.

2001-01-01

Two strains of freshwater-reared coho salmon Oncorhynchus kisutch were compared for differences in the activity of selected non-specific immune factors before and after lethal and non-lethal immersion challenges with the marine bacterial pathogen Vibrio anguillarum (Vang). Two disease challenge experiments were performed. The first experimental challenge resulted in no mortality; however, significant strain and challenge treatment effects were detected at Day 16 post-challenge. Strain differences in plasma lysozyme activity were found in pre-challenge samples. The second challenge experiment compared the same strains of coho salmon following immersion challenges in different doses of Vang. The fish were sampled at Days 0, 2, 7, and 18 post-challenge and mortality, plasma lysozyme, and anterior kidney phagocyte respiratory burst activity were compared. There were significant strain differences in mortality in the high dose group. The more disease-resistant strain was found to have higher levels of plasma lysozyme and anterior kidney phagocyte respiratory burst activity. These strain differences were detected at various times in the lethal (high dose) and non-lethal challenge groups. There was a clear relationship between the enhanced survival of the more disease-resistant strain and a more sustained, elevated non-specific immune response following the experimental disease challenges. The results of this study suggest that the basis for strain differences in innate disease resistance is related to the ability of the fish to respond quickly to the initial infection and to maintain the response until the infection is quelled.

Neural efficiency as a function of task demands☆

PubMed Central

Dunst, Beate; Benedek, Mathias; Jauk, Emanuel; Bergner, Sabine; Koschutnig, Karl; Sommer, Markus; Ischebeck, Anja; Spinath, Birgit; Arendasy, Martin; Bühner, Markus; Freudenthaler, Heribert; Neubauer, Aljoscha C.

2014-01-01

The neural efficiency hypothesis describes the phenomenon that brighter individuals show lower brain activation than less bright individuals when working on the same cognitive tasks. The present study investigated whether the brain activation–intelligence relationship still applies when more versus less intelligent individuals perform tasks with a comparable person-specific task difficulty. In an fMRI-study, 58 persons with lower (n = 28) or respectively higher (n = 30) intelligence worked on simple and difficult inductive reasoning tasks having the same person-specific task difficulty. Consequently, less bright individuals received sample-based easy and medium tasks, whereas bright subjects received sample-based medium and difficult tasks. This design also allowed a comparison of lower versus higher intelligent individuals when working on the same tasks (i.e. sample-based medium task difficulty). In line with expectations, differences in task performance and in brain activation were only found for the subset of tasks with the same sample-based task difficulty, but not when comparing tasks with the same person-specific task difficulty. These results suggest that neural efficiency reflects an (ability-dependent) adaption of brain activation to the respective task demands. PMID:24489416

Natural and man-made radioactivity in soils and plants around the research reactor of Inshass.

PubMed

Higgy, R H; Pimpl, M

1998-12-01

The specific radioactivities of the U-series, 232Th, 137Cs and 40K were measured in soil samples around the Inshass reactor in Cairo, using a gamma-ray spectrometer with a HpGe detector. The alpha activity of 238U, 234U and 235U was measured in the same soil samples by surface barrier detectors after radiochemical separation and the obtained results were compared with the specific activities determined by gamma-measurements. The alpha-activity of 238Pu, 239+240Pu, 241Am, 242Cm and 244Cm was measured after radiochemical separation by surface barrier detectors for both soil and plant samples. Then beta-activity of 241Pu was measured using liquid scintillation spectrometry.

Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor

PubMed Central

Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L.; Minassian, Arpi

2016-01-01

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature. PMID:27138818

Bovine protoporphyria: documentation of autosomal recessive inheritance and comparison with the human disease through measurement of heme synthase activity.

PubMed Central

Bloomer, J R; Morton, K O; Reuter, R J; Ruth, G R

1982-01-01

Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin fibroblasts and whole liver homogenates from animals with protoporphyria, their unaffected parents, and normal cattle in order to examine the mode of inheritance and compare it with human protoporphyria. The mean activity (+/- SEM) in fibroblasts from the three groups was 2.0 +/- 0.4, 47 +/- 12, and 149 +/- 10 pmol heme formed/mg protein per hr, respectively, consistent with autosomal recessive inheritance. Similarly, the levels of heme synthase activity in livers of the parents were intermediate to those of normal animals and of animals with protoporphyria. When compared with normal human fibroblasts and liver, the specific activity of heme synthase in normal bovine tissue was significantly higher. These studies indicate that manifestations of protoporphyria do not occur in cattle unless the animal is homozygous for the gene defect, whereas in humans, the heterozygous condition is sufficient. This is probably because the specific activity of heme synthase in cells of heterozygous animals is not reduced to a level that significantly alters heme metabolism. PMID:7072720

The development and characterization of an ELISA specifically detecting the active form of cathepsin K.

PubMed

Sun, S; Karsdal, M A; Bay-Jensen, A C; Sørensen, M G; Zheng, Q; Dziegiel, M H; Maksymowych, W P; Henriksen, K

2013-10-01

Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosis or ankylosing spondylitis. Presently there are no robust assays for the assessment of active cathepsin K in serum, and therefore an ELISA specifically detecting the N-terminal of the active form of cathepsin K was developed. The assay was technically robust, with a lowest limit of detection (LOD) of 0.085 ng/mL. The average intra- and inter-assay CV% were 6.60% and 8.56% respectively. The dilution recovery and spike recovery tests in human serum were within 100±20% within the range of the assay. A comparison of latent and active cathepsin K confirmed specificity towards the active form. Quantification of the levels of active cathepsin K in supernatants of purified human osteoclasts compared to corresponding macrophages showed a 30-fold induction (p<0.001). In contrast, in serum samples from osteoporotic women on estrogen or bisphosphonate therapy and from ankylosing spondylitis patients no clinically relevant differences were observed. In summary, we have developed a robust and sensitive assay specifically detecting the active form of cathepsin K; however, while it monitors osteoclasts with high specificity in vitro, it appears that circulating levels of active cathepsin K do not reflect bone changes under these circumstances. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Respiratory Syncytial Virus (RSV): Neutralizing Antibody, a Correlate of Immune Protection.

PubMed

Piedra, Pedro A; Hause, Anne M; Aideyan, Letisha

2016-01-01

Assays that measure RSV-specific neutralizing antibody activity are very useful for evaluating vaccine candidates, performing seroprevalence studies, and detecting infection. Neutralizing antibody activity is normally measured by a plaque reduction neutralization assay or by a microneutralization assay with or without complement. These assays measure the functional capacity of serum (or other fluids) to neutralize virus infectivity in cells as compared to ELISA assays that only measure the binding capacity against an antigen. This chapter discusses important elements in standardization of the RSV-specific microneutralization assay for use in the laboratory.

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.

Some Lactobacillus l-Lactate Dehydrogenases Exhibit Comparable Catalytic Activities for Pyruvate and Oxaloacetate

PubMed Central

Arai, Kazuhito; Kamata, Takeo; Uchikoba, Hiroyuki; Fushinobu, Shinya; Matsuzawa, Hiroshi; Taguchi, Hayao

2001-01-01

The nonallosteric and allosteric l-lactate dehydrogenases of Lactobacillus pentosus and L. casei, respectively, exhibited broad substrate specificities, giving virtually the same maximal reaction velocity and substrate Km values for pyruvate and oxaloacetate. Replacement of Pro101 with Asn reduced the activity of the L. pentosus enzyme toward these alternative substrates to a greater extent than the activity toward pyruvate. PMID:11114942

Calculation of single-pass gain for laser ceramics with losses

NASA Astrophysics Data System (ADS)

Vatnik, S. M.

2018-04-01

Rate equations describing the single-pass gain in an active medium with losses are analytically solved. The found relations illustrate the dependences of the amplification efficiency of Nd : YAG ceramics on the pump power density and specific losses. It is concluded that specific losses can be estimated from comparative measurements of unsaturated and saturated gains.

Prostate Cancer Disparities in an Incarcerated Community

DTIC Science & Technology

2012-09-01

smoking habits , dietary intake, physical activity levels, anthropometrics, sun exposure, frequency of general health care utilization and prostate...such as impactful conversations and exposures, others are tangible and noteworthy and listed below. (1) Dr. Borysova accepted an invitation to...SOW has been retained. Specific Aims Specific Aim 1: Compare the lifestyle factors thought to be associated with prostate cancer including

Engineering Neprilysin Activity and Specificity to Create a Novel Therapeutic for Alzheimer’s Disease

PubMed Central

Webster, Carl I.; Burrell, Matthew; Olsson, Lise-Lotte; Fowler, Susan B.; Digby, Sarah; Sandercock, Alan; Snijder, Arjan; Tebbe, Jan; Haupts, Ulrich; Grudzinska, Joanna; Jermutus, Lutz; Andersson, Christin

2014-01-01

Neprilysin is a transmembrane zinc metallopeptidase that degrades a wide range of peptide substrates. It has received attention as a potential therapy for Alzheimer’s disease due to its ability to degrade the peptide amyloid beta. However, its broad range of peptide substrates has the potential to limit its therapeutic use due to degradation of additional peptides substrates that tightly regulate many physiological processes. We sought to generate a soluble version of the ectodomain of neprilysin with improved activity and specificity towards amyloid beta as a potential therapeutic for Alzheimer’s disease. Extensive amino acid substitutions were performed at positions surrounding the active site and inner surface of the enzyme and variants screened for activity on amyloid beta 1–40, 1–42 and a variety of other physiologically relevant peptides. We identified several mutations that modulated and improved both enzyme selectivity and intrinsic activity. Neprilysin variant G399V/G714K displayed an approximately 20-fold improved activity on amyloid beta 1–40 and up to a 3,200-fold reduction in activity on other peptides. Along with the altered peptide substrate specificity, the mutant enzyme produced a markedly altered series of amyloid beta cleavage products compared to the wild-type enzyme. Crystallisation of the mutant enzyme revealed that the amino acid substitutions result in alteration of the shape and size of the pocket containing the active site compared to the wild-type enzyme. The mutant enzyme offers the potential for the more efficient degradation of amyloid beta in vivo as a therapeutic for the treatment of Alzheimer’s disease. PMID:25089527

Combined Functional and Immunochemical Analysis of Normal and Abnormal Human Factor X

PubMed Central

Fair, Daryl S.; Plow, Edward F.; Edgington, Thomas S.

1979-01-01

Human Factor X was isolated from Cohn fraction III and characterized by polyacrylamide gel electrophoresis, amino acid composition, and isoelectric focusing. Two molecular forms with biological activity were observed at isoelectric points of 4.8 and 5.0. Antisera generated to Factor X was monospecific and used to establish an equilibrium competitive inhibition radioimmunoassay. This assay was specific for human Factor X and did not cross-react with human prothrombin or bovine Factor X within the sensitivity range of 6-300 ng Factor X antigen/ml. The mean concentration of Factor X based on the antigen was 11.9 μg/ml, whereas concentration values based on coagulant activity was 7.8 μg/ml. This 30% difference in measurement appears to result from the presence of a subpopulation of Factor X molecules devoid of coagulant activity. The radioimmunoassay was used to qualitatively and quantitatively compare purified Factor X to plasmic Factor X obtained from normal, warfarintreated, acquired Factor X-deficient, and congenitaldeficient patients. In all but one case, the Factor X present in these plasmas was immunochemically identical to the purified Factor X and permitted precise quantitation of these abnormal Factor X molecules. Factor X procoagulant activity was analyzed relative to Factor X antigen and the specific activities were used to characterize normal and abnormal Factor X molecules. Reduced Factor X activity in plasmas from warfarin-treated and acquired Factor X-deficient patients was attributed to both decreases in Factor X antigen and decreased function of the Factor X molecules. Congenitally deficient patients, in general, showed a reduction in Factor X antigen in parallel with Factor X procoagulant activities resulting from comparable decreases in specific biological activity of the molecules. Images PMID:90058

Natural radioactive contaminants in solder

NASA Astrophysics Data System (ADS)

Bunzl, K.; Kracke, W.

1985-07-01

Comparatively high surface count rates for alpha- and beta-radiation were observed for several solders. They were identified as 210Pb and 210Po. The corresponding specific activities in solder were determined.

Acupuncture inhibits cue-induced heroin craving and brain activation.

PubMed

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-11-25

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

The Attributable Proportion of Specific Leisure-Time Physical Activities to Total Activity Volume Among US Adults, National Health and Nutrition Examination Survey 1999–2006

PubMed Central

Watson, Kathleen B.; Dai, Shifan; Paul, Prabasaj; Carlson, Susan A.; Carroll, Dianna D.; Fulton, Janet E.

2017-01-01

Background Previous studies have examined participation in specific leisure-time physical activities (PA) among US adults. The purpose of this study was to identify specific activities that contribute substantially to total volume of leisure-time PA in US adults. Methods Proportion of total volume of leisure-time PA moderate-equivalent minutes attributable to 9 specific types of activities was estimated using self-reported data from 21,685 adult participants (≥ 18 years) in the National Health and Nutrition Examination Survey 1999–2006. Results Overall, walking (28%), sports (22%), and dancing (9%) contributed most to PA volume. Attributable proportion was higher among men than women for sports (30% vs. 11%) and higher among women than men for walking (36% vs. 23%), dancing (16% vs. 4%), and conditioning exercises (10% vs. 5%). The proportion was lower for walking, but higher for sports, among active adults than those insufficiently active and increased with age for walking. Compared with other racial/ethnic groups, the proportion was lower for sports among non-Hispanic white men and for dancing among non-Hispanic white women. Conclusions Walking, sports, and dance account for the most activity time among US adults overall, yet some demographic variations exist. Strategies for PA promotion should be tailored to differences across population subgroups. PMID:27335226

Problem Solving Activity in the Workplace and the School: The Case of Constructing Solids.

ERIC Educational Resources Information Center

Jurdak, Murad; Shahin, Iman

2001-01-01

Documents, compares, and analyzes the nature of spatial reasoning by practitioners (plumbers) in the workplace and students in the school setting while constructing solids, with given specifications, from plane surfaces. Results confirm the power of activity theory and its methodology in explaining and identifying the structural differences…

Development of Intellectual Activity in Solving Exponential Inequalities

ERIC Educational Resources Information Center

Alpyssov, Akan; Mukanova, Zhazira; Kireyeva, Assel; Sakenov, Janat; Kervenev, Kabylgazy

2016-01-01

The article describes the possibilities and the main directions of development of intellectual activity in teaching mathematics in school. The aims and specific features of application of international comparative TIMSS and PISA studies, as well as their results in the field of mathematics education in relation to the pupils in Kazakhstan are…

Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

ERIC Educational Resources Information Center

Giovanello, Kelly S.; Schacter, Daniel L.

2012-01-01

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults--individuals who exhibit behavioral declines in relational memory--would show…

Guide for Occupational Exploration: Activities in Career and Self-Assessment. Counselor Edition.

ERIC Educational Resources Information Center

Ryan, Thomas P.

The self- and career-assessment activities contained in this booklet, together with the summary sheet (score card) which each student will produce, provide a structured process for students to examine their preferences, aptitudes, and value systems and compare them with the requirements and attributes of thirty-five specific careers. Aimed…

Task-Dependent Modulations of Prefrontal and Hippocampal Activity during Intrinsic Word Production

ERIC Educational Resources Information Center

Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

2009-01-01

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on…

The Instrument for the Observation of Teaching Activities (IOTA) and Alternative Approaches to Remediation of Teacher Weaknesses.

ERIC Educational Resources Information Center

Richardson, Donald C.; Hatley, Richard V.

1980-01-01

Comparing the effectiveness of different strategies for remediating teacher weaknesses, as measured by the Instrument for Observation of Teaching Activities (IOTA), 99 elementary and junior high school teachers were observed. The study revealed that combining IOTA feedback with structured inservice workshops focusing on narrow specific weaknesses…

Do Specific Classroom Reading Activities Predict English Language Learners' Later Reading Achievement?

ERIC Educational Resources Information Center

Swanson, H. Lee; Orosco, Michael J.; Kudo, Milagros Fatima

2017-01-01

This study investigated the relationship between elementary classroom (N = 50) reading activities in Year 1 and reading performance (i.e., passage comprehension, letter-word identification, and word attack) 1 year later for English language learners (ELLs; N = 270). A cross-classification hierarchical model indicated that compared to other reading…

CYP1A1 and CYP1A2 expression: Comparing ‘humanized’ mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

PubMed Central

Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.

2009-01-01

Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how “human-like” can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1_CYP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+)_severe-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs. PMID:19285097

CYP1A1 and CYP1A2 expression: Comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

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

Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji

2009-05-15

Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1{sub C}YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carryingmore » humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+){sub s}evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.« less

Simultaneous measurement of two enzyme activities using infrared spectroscopy: A comparative evaluation of PARAFAC, TUCKER and N-PLS modeling.

PubMed

Baum, Andreas; Hansen, Per Waaben; Meyer, Anne S; Mikkelsen, Jørn Dalgaard

2013-08-06

Enzymes are used in many processes to release fermentable sugars for green production of biofuel, or the refinery of biomass for extraction of functional food ingredients such as pectin or prebiotic oligosaccharides. The complex biomasses may, however, require a multitude of specific enzymes which are active on specific substrates generating a multitude of products. In this paper we use the plant polymer, pectin, to present a method to quantify enzyme activity of two pectolytic enzymes by monitoring their superimposed spectral evolutions simultaneously. The data is analyzed by three chemometric multiway methods, namely PARAFAC, TUCKER3 and N-PLS, to establish simultaneous enzyme activity assays for pectin lyase and pectin methyl esterase. Correlation coefficients Rpred(2) for prediction test sets are 0.48, 0.96 and 0.96 for pectin lyase and 0.70, 0.89 and 0.89 for pectin methyl esterase, respectively. The retrieved models are compared and prediction test sets show that especially TUCKER3 performs well, even in comparison to the supervised regression method N-PLS. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of reactive oxygen species in the anticancer activity of botanicals: Comparing sensitivity profiles

PubMed Central

Cohen, Zoya; Maimon, Yair; Samuels, Noah; Berger, Raanan

2017-01-01

Numerous botanicals have been shown to exhibit in vitro and in vivo anticancer activity, some of which is the result of the induction of reactive oxygen species (ROS) in cancer cells with a high ROS content. The present study compared sensitivities to a series of botanicals among cancer cell lines, using an XTT viability test, in order to create a specific cancer-herb profile. Of the 27 botanicals screened, 10 exhibited a cytotoxic effect, 7 of which were ROS-mediated. The sensitivity profiles of the ROS-inducing botanicals in 10 cancer cell lines were similar, unlike 3 cytotoxic ROS-independent botanicals that displayed divergent botanical-specific profiles. The correlation between sensitivity profiles of ROS-inducing botanicals suggests a common mechanism of action, in contrast to the varied mechanism of ROS-independent botanicals. This implies that the investigation of the anticancer activity of botanicals should start with the examination of ROS-mediated activity. Further investigation of ROS sensitivity among various tumor types is required in order to guide research into developing evidence-based guidelines in the use of botanicals for cancer treatment. PMID:28454445

A hypoallergenic variant of the major birch pollen allergen shows distinct characteristics in antigen processing and T-cell activation.

PubMed

Kitzmüller, C; Wallner, M; Deifl, S; Mutschlechner, S; Walterskirchen, C; Zlabinger, G J; Ferreira, F; Bohle, B

2012-11-01

BM4 is a novel genetically engineered variant of the major birch pollen allergen Bet v 1 that lacks the typical Bet v 1-like fold and displays negligible IgE-binding but strong T cell-activating capacity. The aim of this study was to elucidate possible differences between BM4 and Bet v 1 in internalization, antigen processing, and presentation. Proliferative responses to BM4 and Bet v 1 of peripheral blood mononuclear cells and Bet v 1-specific T-cell clones were compared. Fluorescently labeled BM4 and Bet v 1 were used to study surface binding, endocytosis, and intracellular degradation by monocyte-derived DC (mdDC). Both proteins were digested by endolysosomal extracts of mdDC. BM4- and Bet v 1-pulsed mdDC were employed to assess the kinetics of activation of Bet v 1-specific T-cell clones and the polarization of naïve T cells. BM4 displayed a significantly stronger T cell-activating capacity than Bet v 1. Furthermore, BM4 showed increased surface binding and internalization as well as faster endolysosomal degradation compared with Bet v 1. BM4-pulsed mdDC induced enhanced proliferative responses at earlier time-points in Bet v 1-specific T-cell clones and promoted less IL-5 production in T cells than Bet v 1-pulsed mdDC. The loss of the Bet v 1-fold changes the protein's interaction with the human immune system at the level of antigen-presenting cells resulting in altered T-cell responses. By combining low IgE-binding with strong and modulating T cell-activating capacity, BM4 represents a highly interesting candidate for specific immunotherapy of birch pollen allergy. © 2012 John Wiley & Sons A/S.

Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis.

PubMed

Greiner, Alexander; Plischke, Herbert; Kellner, Herbert; Gruber, Rudolf

2005-06-01

We evaluated the association of anti-cyclic citrullinated peptide (CCP) antibody titers with serological markers of disease activity. We also compared three different anti-CCP antibody ELISAs with an anti-citrullin ELISA and the IgM and the IgA rheumatoid factor (RF) in their performance of discriminating between rheumatoid arthritis (RA) and other rheumatic diseases. Sera from 333 consecutive patients of the Rheumaeinheit der Medizinischen Poliklinik Munchen, an outpatient clinic for rheumatic diseases, were collected and tested. Anti-CCP antibodies were assayed with three different commercially available ELISAs. Antifilaggrin antibodies were tested with a commercially available ELISA using in vitro deiminated recombinant rat filaggrin. IgA-RF was analyzed with an ELISA, whereas IgM-RF was measured by latex-enhanced turbidimetry. Rheumatoid arthritis (RA) was diagnosed in 87 patients according to the revised classification criteria of the American College of Rheumatology (ACR), probable RA was diagnosed in 23 patients in an early phase not (yet) fulfilling the ACR criteria, and 223 patients had other rheumatic diseases. Differences in sensitivity and specificity were calculated using McNemar's test. A measure of agreement (kappa statistic) was used to examine whether the tests tended to identify the same patients as positive or negative. Correlations between CCP titers and other tests were analyzed by Spearman nonparametric rank correlation. No significant differences in sensitivity and specificity were found between the tested CCP assays (80.0-80.9% and 97.3-98.1%, respectively). All three CCP tests were slightly but not significantly more sensitive and specific than the anti-citrullin assay (77% and 92%, respectively), comparably sensitive but significantly more specific compared with the IgM-RF (86% and 82%, respectively), and significantly more sensitive but comparably specific compared with the IgA-RF (63% and 94.4%, respectively) in detecting the patients with RA. There was no significant correlation between anti-CCP, anti-citrullin, or IgM-RF or IgA-RF antibody titers and C-reactive protein, erythrocyte sedimentation rate, or white blood cell count. A weak but significant linear correlation was found between anti-CCP titers and IgM-RF titers (r = 0.2, P = 0.03). We could not find a significant difference between the three tested anti-CCP assays and the anti-citrullin test in terms of sensitivity and specificity. Compared with the IgM-RF, all the anti-CCP assays were superior in specificity and comparable in sensitivity. Compared with the IgA-RF, they were more sensitive and comparably specific in the discrimination of patients with RA from other rheumatic diseases. No correlation of any tested autoantibody titer with serological parameters of inflammation was found.

Contrast-enhanced MRI compared with the physical examination in the evaluation of disease activity in juvenile idiopathic arthritis.

PubMed

Hemke, Robert; Maas, Mario; van Veenendaal, Mira; Dolman, Koert M; van Rossum, Marion A J; van den Berg, J Merlijn; Kuijpers, Taco W

2014-02-01

To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients. Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6% female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9%) with clinically inactive disease. Of JIA patients considered clinically active, 48.6% showed no signs of MRI-based synovitis. MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35% of presumed clinically inactive patients. • MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity. • Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients. • Subclinical synovitis is present in 35.9 % of presumed clinically inactive patients. • Physical examination is neither sensitive nor specific in evaluating JIA disease activity.

Flavones in citrus exhibit antiadhesive action on platelets.

PubMed

Robbins, R C

1988-01-01

Two methoxylated flavones isolated from citrus, sinensetin (5 methoxyls) and heptamethoxy flavone (7 methoxyls), were compared in vitro with nobiletin for antiadhesive activity on rat platelets. Nobiletin (a hexamethoxyflavone also isolated from citrus) has been previously shown by several workers to have antiadhesive and antithrombogenic activity. The penta- and heptamethoxylated flavones exhibited anti-adhesive activity similar to that of nobiletin. However, activity did not parallel number of methoxyl groups which appear to indicate some degree of specificity between flavone structure and antiadhesive activity on platelets.

Undergraduate Student Attitudes and Perceptions toward Low- and High-Level Inquiry Exercise Physiology Teaching Laboratory Experiences

ERIC Educational Resources Information Center

Henige, Kim

2011-01-01

The purpose of this investigation was to compare student attitudes toward two different science laboratory learning experiences, specifically, traditional, cookbook-style, low-inquiry level (LL) activities and a high-inquiry level (HL) investigative project. In addition, we sought to measure and compare students' science-related attitudes and…

Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes

PubMed Central

Tie, Lu; Li, Xue-Jun; Wang, Xian; Channon, Keith M.; Chen, Alex F.

2009-01-01

Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH4). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH4 synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH4 level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O2−) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O2− level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH4 overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress. PMID:19336662

A Cell-Line-Specific Atlas of PARP-Mediated Protein Asp/Glu-ADP-Ribosylation in Breast Cancer.

PubMed

Zhen, Yuanli; Zhang, Yajie; Yu, Yonghao

2017-11-21

PARP1 plays a critical role in regulating many biological processes linked to cellular stress responses. Although DNA strand breaks are potent stimuli of PARP1 enzymatic activity, the context-dependent mechanism regulating PARP1 activation and signaling is poorly understood. We performed global characterization of the PARP1-dependent, Asp/Glu-ADP-ribosylated proteome in a panel of cell lines originating from benign breast epithelial cells, as well as common subtypes of breast cancer. From these analyses, we identified 503 specific ADP-ribosylation sites on 322 proteins. Despite similar expression levels, PARP1 is differentially activated in these cell lines under genotoxic conditions, which generates signaling outputs with substantial heterogeneity. By comparing protein abundances and ADP-ribosylation levels, we could dissect cell-specific PARP1 targets that are driven by unique expression patterns versus cell-specific regulatory mechanisms of PARylation. Intriguingly, PARP1 modifies many proteins in a cell-specific manner, including those involved in transcriptional regulation, mRNA metabolism, and protein translation. Copyright © 2017 The Author(s). Published by 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.

Neural network versus activity-specific prediction equations for energy expenditure estimation in children.

PubMed

Ruch, Nicole; Joss, Franziska; Jimmy, Gerda; Melzer, Katarina; Hänggi, Johanna; Mäder, Urs

2013-11-01

The aim of this study was to compare the energy expenditure (EE) estimations of activity-specific prediction equations (ASPE) and of an artificial neural network (ANNEE) based on accelerometry with measured EE. Forty-three children (age: 9.8 ± 2.4 yr) performed eight different activities. They were equipped with one tri-axial accelerometer that collected data in 1-s epochs and a portable gas analyzer. The ASPE and the ANNEE were trained to estimate the EE by including accelerometry, age, gender, and weight of the participants. To provide the activity-specific information, a decision tree was trained to recognize the type of activity through accelerometer data. The ASPE were applied to the activity-type-specific data recognized by the tree (Tree-ASPE). The Tree-ASPE precisely estimated the EE of all activities except cycling [bias: -1.13 ± 1.33 metabolic equivalent (MET)] and walking (bias: 0.29 ± 0.64 MET; P < 0.05). The ANNEE overestimated the EE of stationary activities (bias: 0.31 ± 0.47 MET) and walking (bias: 0.61 ± 0.72 MET) and underestimated the EE of cycling (bias: -0.90 ± 1.18 MET; P < 0.05). Biases of EE in stationary activities (ANNEE: 0.31 ± 0.47 MET, Tree-ASPE: 0.08 ± 0.21 MET) and walking (ANNEE 0.61 ± 0.72 MET, Tree-ASPE: 0.29 ± 0.64 MET) were significantly smaller in the Tree-ASPE than in the ANNEE (P < 0.05). The Tree-ASPE was more precise in estimating the EE than the ANNEE. The use of activity-type-specific information for subsequent EE prediction equations might be a promising approach for future studies.

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

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.

Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy

PubMed Central

Yamada, Shinichiro; Hashizume, Atsushi; Hijikata, Yasuhiro; Inagaki, Tomonori; Suzuki, Keisuke; Kondo, Naohide; Kawai, Kaori; Noda, Seiya; Nakanishi, Hirotaka; Banno, Haruhiko; Hirakawa, Akihiro; Koike, Haruki; Halievski, Katherine; Jordan, Cynthia L.; Katsuno, Masahisa; Sobue, Gen

2016-01-01

The aim of this study was to characterize the respiratory function profile of subjects with spinal and bulbar muscular atrophy (SBMA), and to explore the underlying pathological mechanism by comparing the clinical and biochemical indices of this disease with those of amyotrophic lateral sclerosis (ALS). We enrolled male subjects with SBMA (n = 40) and ALS (n = 25) along with 15 healthy control subjects, and assessed their respiratory function, motor function, and muscle strength. Predicted values of peak expiratory flow (%PEF) and forced vital capacity were decreased in subjects with SBMA compared with controls. In SBMA, both values were strongly correlated with the trunk subscores of the motor function tests and showed deterioration relative to disease duration. Compared with activities of daily living (ADL)-matched ALS subjects, %PEF, tongue pressure, and grip power were substantially decreased in subjects with SBMA. Both immunofluorescence and RT-PCR demonstrated a selective decrease in the expression levels of the genes encoding the myosin heavy chains specific to fast-twitch fibers in SBMA subjects. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and peroxisome proliferator-activated receptor delta were up-regulated in SBMA compared with ALS and controls. In conclusion, %PEF is a disease-specific respiratory marker for the severity and progression of SBMA. Explosive muscle strength, including %PEF, was selectively affected in subjects with SBMA and was associated with activation of the mitochondrial biogenesis-related molecular pathway in skeletal muscles. PMID:28005993

Lectins: production and practical applications

PubMed Central

2010-01-01

Lectins are proteins found in a diversity of organisms. They possess the ability to agglutinate erythrocytes with known carbohydrate specificity since they have at least one non-catalytic domain that binds reversibly to specific monosaccharides or oligosaccharides. This articles aims to review the production and practical applications of lectins. Lectins are isolated from their natural sources by chromatographic procedures or produced by recombinant DNA technology. The yields of animal lectins are usually low compared with the yields of plant lectins such as legume lectins. Lectins manifest a diversity of activities including antitumor, immunomodulatory, antifungal, HIV-1 reverse transcriptase inhibitory, and anti-insect activities, which may find practical applications. A small number of lectins demonstrate antibacterial and anti-nematode activities. PMID:20890754

Acupuncture inhibits cue-induced heroin craving and brain activation★

PubMed Central

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-01-01

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

Evidence that the platelet plasma membrane does not contain a (Ca2+ + Mg2+)-dependent ATPase.

PubMed

Steiner, B; Lüscher, E F

1985-09-10

The present study was designed to determine the subcellular distribution of the platelet (Ca2+ + Mg2+)-ATPase. Human platelets were surface labeled by the periodate-boro[3H]hydride method. Plasma membrane vesicles were then isolated to a purity of approx. 90% by a procedure utilizing wheat germ agglutinin affinity chromatography. These membranes were found to be 2.6-fold enriched in surface glycoproteins compared to an unfractionated vesicle fraction and almost 7-fold enriched compared to intact platelets. In contrast, the isolated plasma membranes showed a decreased specific activity of the (Ca2+ + Mg2+)-ATPase compared to the unfractionated vesicle fraction. This decrease in specific activity was found to be similar to that of an endoplasmic reticulum marker, glucose-6-phosphatase, and to that of a platelet inner membrane marker, phospholipase A2. We conclude, therefore, that the (Ca2+ + Mg2+)-ATPase is not located in the platelet plasma membrane but is restricted to membranes of intracellular origin.

The Structure of Walking Activity in People After Stroke Compared With Older Adults Without Disability: A Cross-Sectional Study

PubMed Central

Roos, Margaret A.; Rudolph, Katherine S.

2012-01-01

Background People with stroke have reduced walking activity. It is not known whether this deficit is due to a reduction in all aspects of walking activity or only in specific areas. Understanding specific walking activity deficits is necessary for the development of interventions that maximize improvements in activity after stroke. Objective The purpose of this study was to examine walking activity in people poststroke compared with older adults without disability. Design A cross-sectional study was conducted. Methods Fifty-four participants poststroke and 18 older adults without disability wore a step activity monitor for 3 days. The descriptors of walking activity calculated included steps per day (SPD), bouts per day (BPD), steps per bout (SPB), total time walking per day (TTW), percentage of time walking per day (PTW), and frequency of short, medium, and long walking bouts. Results Individuals classified as household and limited community ambulators (n=29) did not differ on any measure and were grouped (HHA-LCA group) for comparison with unlimited community ambulators (UCA group) (n=22) and with older adults without disability (n=14). The SPD, TTW, PTW, and BPD measurements were greatest in older adults and lowest in the HHA-LCA group. Seventy-two percent to 74% of all walking bouts were short, and this finding did not differ across groups. Walking in all categories (short, medium, and long) was lowest in the HHA-LCA group, greater in the UCA group, and greatest in older adults without disability. Limitations Three days of walking activity were captured. Conclusions The specific descriptors of walking activity presented provide insight into walking deficits after stroke that cannot be ascertained by looking at steps per day alone. The deficits that were revealed could be addressed through appropriate exercise prescription, underscoring the need to analyze the structure of walking activity. PMID:22677293

Specific activity of natural and anthropogenic radionuclides and radiological hazard assessment in surface soil samples collected along the Andaman sea coast in southern region of Thailand

NASA Astrophysics Data System (ADS)

Kessaratikoon, P.; Boonkrongcheep, R.; Benjakul, S.; Udomsomporn, S.

2015-05-01

The specific activities of natural (40K, 226Ra and 232Th) and anthropogenic radionuclides (137Cs) in 314 surface soil samples collected from three provinces (Phuket, Phang-Nga and Krabi) along the Andaman sea coast in southern region of Thailand were studied and evaluated. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system. It was found that the mean values of specific activities of 40K, 226Ra, 232Th and 137Cs were 2859.63 ± 209.83, 157.10 ± 8.06, 137.16 ± 7.26 and 4.88 ± 2.34 Bq/kg, respectively. Furthermore, four radiological hazard indices which are absorbed dose rate in air (D), radium equivalent activity (Raeq), external hazard index (Hex) and annual effective dose rate (AEDout) in the area under consideration were also calculated and came out to be 277.11 ± 16.96 nGy/h, 575.16 ± 34.67 Bq/kg, 1.55 ± 0.09 and 0.34 ± 0.02 mSv/y, respectively. The experimental results were also compared and found to be comparable with national and global radioactivity measurements and evaluations. Moreover, the radioactive contour maps of the investigated area were also created and presented in this paper.

Radical Prostatectomy Findings in Men on Active Surveillance: Variable Findings Dependent on Reason for Surgery and Entry Criteria.

PubMed

Matoso, Andres; Hassan, Oudai; Petrozzino, Florencia; Rao, B Vishal; Carter, H Ballentine; Epstein, Jonathan I

2015-09-01

We studied adverse radical prostatectomy findings in men on an active surveillance program with different entry and exit criteria. The study included 80 men with biopsy progression, 33 who opted out for personal reasons and 24 who initially did not meet entry criteria mainly due to increased prostate specific antigen density. Of men who opted out 78.8% had a higher Gleason score of 6 than men who progressed on biopsy (46.2%, p = 0.002) and men with high prostate specific antigen density (45.8%, p = 0.02). Men with high prostate specific antigen density had less organ confined disease than the group that opted out (p <0.006) and a trend compared to the biopsy progression group (p = 0.07). Mean dominant tumor volume was lower in men who opted out than in those with biopsy progression (0.56 vs 1.1 cc, p = 0.03). The incidence of insignificant cancer was higher in men who opted out (48.4%) than in those with biopsy progression (28.4%, p = 0.05) and those with high prostate specific antigen density (20.8%, p = 0.035). There was a higher incidence of anterior tumor in men with high prostate specific antigen density (55.0%) than with biopsy progression (21.3%, p = 0.009) and a trend compared to those who opted out (27.3%, p = 0.06). The majority of men with biopsy progression still had tumors with features of curable disease. Men who opted out without biopsy progression had even less adverse findings, which supports counseling men to stay on active surveillance while they meet followup criteria. Men with elevated prostate specific antigen density had more anterior tumors and less organ confined cancer, substantiating that the ideal patients for active surveillance are those who meet all entry criteria. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

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

Morrison, W.J.

1988-01-01

The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF ormore » thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).« less

Translocator protein as an imaging marker of macrophage and stromal activation in RA pannus.

PubMed

Narayan, Nehal; Owen, David; Mandhair, Harpreet; Smyth, Erica; Carlucci, Francesco; Saleem, Azeem; Gunn, Roger; Rabiner, Eugenii Ilan A; Wells, Lisa; Dakin, Stephanie; Sabokbar, Afsie; Taylor, Peter

2018-01-04

Positron Emission Tomography (PET) radioligands targeted to Translocator protein (TSPO), offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus; monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T lymphocytes, to more accurately interpret TSPO PET signal from RA synovium. Methods: 3 RA patients and 3 healthy volunteers underwent PET both knees using the TSPO radioligand 11 C-PBR28. Through synovial tissue 3H-PBR28 autoradiography and immunostaining of 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO mRNA expression and 3H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS and CD4+ T-lymphocytes. Results: 11 C-PBR28 PET signal was significantly higher in RA compared to healthy joints (average SUV 0.82± 0.12 compared to 0.03± 0.004 respectively, p<0.01). Further, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA compared to healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells. In vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding, in activated FLS, non-activated and activated 'M2' reparative macrophages, with least TSPO expression in activated and non-activated CD4+ T lymphocytes. Conclusion: This study is the first evaluation of cellular TSPO expression in synovium, finding highest TSPO expression and PBR28 binding on activated synovial FLS and M2 phenotype macrophages. TSPO targeted PET may therefore have unique sensitivity to detect FLS and macrophage predominant inflammation in RA, with potential utility to assess treatment response in trials using novel FLS-targeted therapies. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The BPAQ: a bone-specific physical activity assessment instrument.

PubMed

Weeks, B K; Beck, B R

2008-11-01

A newly developed bone-specific physical activity questionnaire (BPAQ) was compared with other common measures of physical activity for its ability to predict parameters of bone strength in healthy, young adults. The BPAQ predicted indices of bone strength at clinically relevant sites in both men and women, while other measures did not. Only certain types of physical activity (PA) are notably osteogenic. Most methods to quantify levels of PA fail to account for bone relevant loading. Our aim was to examine the ability of several methods of PA assessment and a new bone-specific measure to predict parameters of bone strength in healthy adults. We recruited 40 men and women (mean age 24.5). Subjects completed the modifiable activity questionnaire, Bouchard 3-day activity record, a recently published bone loading history questionnaire (BLHQ), and wore a pedometer for 14 days. We also administered our bone-specific physical activity questionnaire (BPAQ). Calcaneal broadband ultrasound attenuation (BUA) (QUS-2, Quidel) and densitometric measures (XR-36, Norland) were examined. Multiple regression and correlation analyses were performed on the data. The current activity component of BPAQ was a significant predictor of variance in femoral neck bone mineral density (BMD), lumbar spine BMD, and whole body BMD (R(2) = 0.36-0.68, p < 0.01) for men, while the past activity component of BPAQ predicted calcaneal BUA (R(2) = 0.48, p = 0.001) for women. The BPAQ predicted indices of bone strength at skeletal sites at risk of osteoporotic fracture while other PA measurement tools did not.

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.

Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

PubMed Central

Gebauer, Daniela; Fink, Andreas; Kargl, Reinhard; Reishofer, Gernot; Koschutnig, Karl; Purgstaller, Christian; Fazekas, Franz; Enzinger, Christian

2012-01-01

Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training. PMID:22693600

Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control.

PubMed

Spetter, Maartje S; Feld, Gordon B; Thienel, Matthias; Preissl, Hubert; Hege, Maike A; Hallschmid, Manfred

2018-02-09

The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed. Oxytocin compared to placebo increased activity in the ventromedial prefrontal cortex, supplementary motor area, anterior cingulate, and ventrolateral prefrontal cortices in response to high- vs. low-calorie food images in the fasted state, and reduced calorie intake by 12%. During anticipation of monetary rewards, oxytocin compared to placebo augmented striatal, orbitofrontal and insular activity without altering MID performance. We conclude that during the anticipation of generalized rewards, oxytocin stimulates dopaminergic reward-processing circuits. In contrast, oxytocin restrains food intake by enhancing the activity of brain regions that exert cognitive control, while concomitantly increasing the activity of structures that process food reward value. This pattern points towards a specific role of oxytocin in the regulation of eating behaviour in humans that might be of relevance for potential clinical applications.

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.

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia.

PubMed

Gozal, Evelyne; Shah, Zahoor A; Pequignot, Jean-Marc; Pequignot, Jacqueline; Sachleben, Leroy R; Czyzyk-Krzeska, Maria F; Li, Richard C; Guo, Shang-Z; Gozal, David

2005-08-01

Tyrosine hydroxylase, a hypoxia-regulated gene, may be involved in tissue adaptation to hypoxia. Intermittent hypoxia, a characteristic feature of sleep apnea, leads to significant memory deficits, as well as to cortex and hippocampal apoptosis that are absent after sustained hypoxia. To examine the hypothesis that sustained and intermittent hypoxia induce different catecholaminergic responses, changes in tyrosine hydroxylase mRNA, protein expression, and activity were compared in various brain regions of male rats exposed for 6 h, 1 day, 3 days, and 7 days to sustained hypoxia (10% O(2)), intermittent hypoxia (alternating room air and 10% O(2)), or normoxia. Tyrosine hydroxylase activity, measured at 7 days, increased in the cortex as follows: sustained > intermittent > normoxia. Furthermore, activity decreased in the brain stem and was unchanged in other brain regions of sustained hypoxia-exposed rats, as well as in all regions from animals exposed to intermittent hypoxia, suggesting stimulus-specific and heterotopic catecholamine regulation. In the cortex, tyrosine hydroxylase mRNA expression was increased, whereas protein expression remained unchanged. In addition, significant differences in the time course of cortical Ser(40) tyrosine hydroxylase phosphorylation were present in the cortex, suggesting that intermittent and sustained hypoxia-induced enzymatic activity differences are related to different phosphorylation patterns. We conclude that long-term hypoxia induces site-specific changes in tyrosine hydroxylase activity and that intermittent hypoxia elicits reduced tyrosine hydroxylase recruitment and phosphorylation compared with sustained hypoxia. Such changes may not only account for differences in enzyme activity but also suggest that, with differential regional brain susceptibility to hypoxia, recruitment of different mechanisms in response to hypoxia will elicit region-specific modulation of catecholamine response.

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

PubMed Central

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-01-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients. PMID:18647321

Gelatin-specific cellular immune responses persist for more than 3 years after priming with gelatin containing DTaP vaccine.

PubMed

Kumagai, T; Kamada, M; Igarashi, C; Yuri, K; Furukawa, H; Nagata, N; Saito, A; Okui, T; Yano, S

2002-10-01

Gelatin-specific cell-mediated immunity develops in subjects inoculated with gelatin containing DTaP vaccine. However, it is not yet known whether such established sensitization to gelatin disappears or persists with time. The aim of this study was to follow the patients with gelatin sensitization elicited by DTaP vaccination for their lymphocyte responsiveness and IgE, IgG antibody specific to gelatin over several years and to compare the activities with those at the time of enrollment into the study. We studied 28 subjects who developed positive lymphocyte proliferation test (LPT) after receiving gelatin containing DTaP vaccine and eight subjects who had a negative LPT after inoculation of non-gelatin DTaP. Determination of IgE, IgG antibodies and specific lymphoproliferative response directed against gelatin were performed at enrollment and on follow up. None of the subjects had antibody to gelatin at enrollment and none developed gelatin IgE or IgG during follow-up. There was no significant difference in the SIs of the subjects receiving gelatin DTaP (P = 0.150, 95% CI, -0.198-0.032), whereas lymphocyte activity to gelatin increased between enrollment and follow-up in the subjects with non-gelatin DTaP (P = 0.011, 95% CI, 0.063-0.338). Gelatin-specific lymphocyte activity persists at comparable levels for more than 3 years in subjects who acquire a positive LPT response to gelatin after receiving primary DTaP vaccine containing gelatin. Furthermore, five out of eight subjects initially with negative LPT to gelatin have been shown to acquire specific LPT with time.

A New Approach to Simulate Groundwater Table Dynamics and Its Validation in China

NASA Astrophysics Data System (ADS)

Lv, M.; Lu, H.; Dan, L.; Yang, K.

2017-12-01

The groundwater has very important role in hydrology-climate-human activity interaction. But the groundwater table dynamics currently is not well simulated in global-scale land surface models. Meanwhile, almost all groundwater schemes are adopting a specific yield method to estimate groundwater table, in which how to determine the proper specific yield value remains a big challenge. In this study, we developed a Soil Moisture Correlation (SMC) method to simulate groundwater table dynamics. We coupled SMC with a hydrological model (named as NEW) and compared it with the original model in which a specific yield method is used (named as CTL). Both NEW and CTL were tested in Tangnaihai Subbasin of Yellow River and Jialingjiang Subbasin along Yangtze River, where underground water is less impacted by human activities. The simulated discharges by NEW and CTL are compared against gauge observations. The comparison results reveal that after calibration both models are able to reproduce the discharge well. However, there is no parameter needed to be calibrated for SMC. It indicates that SMC method is more efficient and easy-to-use than the specific yield method. Since there is no direct groundwater table observation in these two basins, simulated groundwater table were compared with a global data set provided by Fan et al. (2013). Both NEW and CTL estimate lower depths than Fan does. Moreover, when comparing the variation of terrestrial water storage (TWS) derived from NEW with that observed by GRACE, good agreements were confirmed. It demonstrated that SMC method is able to reproduce groundwater level dynamics reliably.

SenseWearMini and Actigraph GT3X Accelerometer Classification of Observed Sedentary and Light-Intensity Physical Activities in a Laboratory Setting.

PubMed

Feehan, Lynne M; Goldsmith, Charles H; Leung, April Y F; Li, Linda C

Purpose: To compare the ability of SenseWear Mini (SWm) and Actigraph GT3X (AG 3 ) accelerometers to differentiate between healthy adults' observed sedentary and light activities in a laboratory setting. Methods: The 22 participants (15 women, 7 men), ages 19 to 72 years, wore SWm and AG 3 monitors and performed five sedentary and four light activities for 5 minutes each while observed in a laboratory setting. Performance was examined through comparisons of accuracy, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Correct identification of both types of activities was examined using area under the receiver operating characteristic curve (AUC). Results: Both monitors demonstrated excellent ability to identify sedentary activities (sensitivity>0.89). The SWm monitor was better at identifying light activities (specificity 0.61-0.71) than the AG 3 monitor (specificity 0.27-0.47) and thus also showed a greater ability to correctly identify both sedentary and light activities (SWm AUC 0.84; AG 3 AUC 0.62-0.73). Conclusions: SWm may be a more suitable monitor for detecting time spent in sedentary and light-intensity activities. This finding has clinical and research relevance for evaluation of time spent in lower intensity physical activities by sedentary adults.

Rapid analysis method for the determination of 14C specific activity in irradiated graphite

PubMed Central

Remeikis, Vidmantas; Lagzdina, Elena; Garbaras, Andrius; Gudelis, Arūnas; Garankin, Jevgenij; Juodis, Laurynas; Duškesas, Grigorijus; Lingis, Danielius; Abdulajev, Vladimir; Plukis, Artūras

2018-01-01

14C is one of the limiting radionuclides used in the categorization of radioactive graphite waste; this categorization is crucial in selecting the appropriate graphite treatment/disposal method. We propose a rapid analysis method for 14C specific activity determination in small graphite samples in the 1–100 μg range. The method applies an oxidation procedure to the sample, which extracts 14C from the different carbonaceous matrices in a controlled manner. Because this method enables fast online measurement and 14C specific activity evaluation, it can be especially useful for characterizing 14C in irradiated graphite when dismantling graphite moderator and reflector parts, or when sorting radioactive graphite waste from decommissioned nuclear power plants. The proposed rapid method is based on graphite combustion and the subsequent measurement of both CO2 and 14C, using a commercial elemental analyser and the semiconductor detector, respectively. The method was verified using the liquid scintillation counting (LSC) technique. The uncertainty of this rapid method is within the acceptable range for radioactive waste characterization purposes. The 14C specific activity determination procedure proposed in this study takes approximately ten minutes, comparing favorably to the more complicated and time consuming LSC method. This method can be potentially used to radiologically characterize radioactive waste or used in biomedical applications when dealing with the specific activity determination of 14C in the sample. PMID:29370233

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.

90Sr specific activity of teeth of abandoned cattle after the Fukushima accident - teeth as an indicator of environmental pollution.

PubMed

Koarai, Kazuma; Kino, Yasushi; Takahashi, Atsushi; Suzuki, Toshihiko; Shimizu, Yoshinaka; Chiba, Mirei; Osaka, Ken; Sasaki, Keiichi; Urushihara, Yusuke; Fukuda, Tomokazu; Isogai, Emiko; Yamashiro, Hideaki; Oka, Toshitaka; Sekine, Tsutomu; Fukumoto, Manabu; Shinoda, Hisashi

2018-03-01

90 Sr specific activity in the teeth of young cattle that were abandoned in Kawauchi village and Okuma town located in the former evacuation areas of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident were measured. Additionally, specific activity in contaminated surface soils sampled from the same area was measured. (1) All cattle teeth examined were contaminated with 90 Sr. The specific activity, however, varied depending on the developmental stage of the teeth during the FNPP accident; teeth that had started development before the accident exhibited comparatively lower values, while teeth developed mainly after the accident showed higher values. (2) Values of 90 Sr-specific activity in teeth formed after the FNPP accident were higher than those of the bulk soil but similar to those in the exchangeable fraction (water and CH 3 COONH 4 soluble fractions) of the soil. The findings suggest that 90 Sr was incorporated into the teeth during the process of development, and that 90 Sr in the soluble and/or leachable fractions of the soil might migrate into teeth and contribute to the amount of 90 Sr in the teeth. Thus, the concentration of 90 Sr in teeth formed after the FNPP accident might reflect the extent of 90 Sr pollution in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid analysis method for the determination of 14C specific activity in irradiated graphite.

PubMed

Remeikis, Vidmantas; Lagzdina, Elena; Garbaras, Andrius; Gudelis, Arūnas; Garankin, Jevgenij; Plukienė, Rita; Juodis, Laurynas; Duškesas, Grigorijus; Lingis, Danielius; Abdulajev, Vladimir; Plukis, Artūras

2018-01-01

14C is one of the limiting radionuclides used in the categorization of radioactive graphite waste; this categorization is crucial in selecting the appropriate graphite treatment/disposal method. We propose a rapid analysis method for 14C specific activity determination in small graphite samples in the 1-100 μg range. The method applies an oxidation procedure to the sample, which extracts 14C from the different carbonaceous matrices in a controlled manner. Because this method enables fast online measurement and 14C specific activity evaluation, it can be especially useful for characterizing 14C in irradiated graphite when dismantling graphite moderator and reflector parts, or when sorting radioactive graphite waste from decommissioned nuclear power plants. The proposed rapid method is based on graphite combustion and the subsequent measurement of both CO2 and 14C, using a commercial elemental analyser and the semiconductor detector, respectively. The method was verified using the liquid scintillation counting (LSC) technique. The uncertainty of this rapid method is within the acceptable range for radioactive waste characterization purposes. The 14C specific activity determination procedure proposed in this study takes approximately ten minutes, comparing favorably to the more complicated and time consuming LSC method. This method can be potentially used to radiologically characterize radioactive waste or used in biomedical applications when dealing with the specific activity determination of 14C in the sample.

Development of Preparatory Activity Indexed by the Contingent Negative Variation in Children

ERIC Educational Resources Information Center

Flores, Angelica B.; Digiacomo, Marcia R.; Meneres, Susana; Trigo, Eva; Gomez, Carlos M.

2009-01-01

Objectives: The present study investigated the effect of age on task-specific preparatory activation induced by a spatial cue using the central cue Posner's paradigm. The behavioral responses and the contingent negative variation (CNV) generated between S1 (the warning stimulus) and S2 (the imperative stimulus) were compared between 16 healthy…

Method for Rapid Purification of Class IIa Bacteriocins and Comparison of Their Activities

PubMed Central

Guyonnet, D.; Fremaux, C.; Cenatiempo, Y.; Berjeaud, J. M.

2000-01-01

A three-step method was developed for the purification of mesentericin Y105 (60% yield) from the culture supernatant of Leuconostoc mesenteroides Y105. The same procedure was successfully applied to the purification of five other anti-Listeria bacteriocins identified by mass spectrometry. Specific activities of the purified bacteriocins were compared. PMID:10742275

Yoga for treatment of urinary incontinence in women

PubMed Central

Wieland, L. Susan; Shrestha, Nipun; Lassi, Zohra S; Panda, Sougata; Chiaramonte, Delia; Skoetz, Nicole

2017-01-01

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness and safety of yoga for treatment of urinary incontinence in women, compared to no specific treatment, to another active treatment, or to an active treatment without adjuvant yoga, with a focus on patient symptoms and quality of life. PMID:29081716

The actin homologue MreB organizes the bacterial cell membrane

PubMed Central

Strahl, Henrik; Bürmann, Frank; Hamoen, Leendert W.

2014-01-01

The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes. PMID:24603761

The actin homologue MreB organizes the bacterial cell membrane.

PubMed

Strahl, Henrik; Bürmann, Frank; Hamoen, Leendert W

2014-03-07

The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes.

Immunological markers of frequently recurrent genital herpes simplex virus and their response to hypnotherapy: a pilot study.

PubMed

Fox, P A; Henderson, D C; Barton, S E; Champion, A J; Rollin, M S; Catalan, J; McCormack, S M; Gruzelier, J

1999-11-01

Patients were recruited for hypnotherapy from a clinic for patients with frequently recurrent genital herpes simplex virus (rgHSV). Psychological and immunological parameters were measured 6 weeks prior to hypnotherapy and 6 weeks afterwards, during which time each patient kept a diary of symptoms of rgHSV. Following hypnotherapy there was a significant overall reduction in the number of reported episodes of rgHSV, accompanied by an increase in the numbers of CD3 and CD8 lymphocytes, which may represent a non specific effect of hypnosis. The improvers showed significant rises in natural killer (NK) cell counts, HSV specific lymphokine activated killer (LAK) activity, and reduced levels of anxiety when compared to non-improvers. NK cell numbers and HSV specific LAK activity may therefore be important in the reduction in rgHSV following hypnotherapy.

Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behçet's disease.

PubMed

Alibaz-Oner, Fatma; Aldag, Belgin; Aldag, Mustafa; Unal, A Ugur; Mutiş, Aydan; Toptas, Tayfur; Ergun, Tulin; Direskeneli, Haner

2016-07-01

Deep venous thrombosis (DVT) is the most common form of vascular involvement in Behçet's disease (BD). Chronic post-thrombotic syndrome (PTS) develops in up to one-half of patients with DVT and is associated with impaired quality of life (QoL). There are no data on the severity of DVT-related PTS and its effect on QoL in patients with vascular BD (VBD). We aimed to evaluate PTS and venous disease-specific QoL in patients with VBD. This study included 50 patients (41 men, nine women) with VBD and 31 individuals matched for age and gender (22 men, nine women) with DVT associated with non-BD causes. The Villalta scale was used to assess PTS. The Venous Disability Score and the Venous Clinical Severity Score were used for the assessment of venous disease. Venous disease-specific QoL was measured through Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES-QoL/Sym) questionnaire. The Behçet Syndrome Activity Score (BSAS) questionnaire was used to assess disease activity. We observed a significantly lower risk of PTS together with significantly better VEINES-QoL/Sym, and Venous Disability Score in the VBD group compared with the non-BD group. When VBD patients with PTS were compared with patients without PTS, VEINES-QoL/Sym, and Venous Clinical Severity Score were significantly worse. BSAS was also significantly higher in patients with PTS. An inverse correlation was found between the VEINES-QoL and the BSAS in multivariate analysis. There were no differences between anticoagulant users and nonusers regarding the presence of PTS and scores of all of the venous assessment tools. We found lower PTS risk and better venous disease-specific QoL, symptom severity, and venous disability scores in VBD patients compared with the non-BD group. Venous disease-specific QoL negatively correlated with disease activity. Effective control of vascular inflammation through treatment in VBD might explain lower rates of PTS and better venous QoL outcomes in VBD patients. Our results suggest that successful control of BD activity might decrease the development of PTS, improve venous disease-specific QoL, and prevent relapses in VBD. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Chemical composition and lipoxygenase activity in soybeans (Glycine max L. Merr.) submitted to gamma irradiation

NASA Astrophysics Data System (ADS)

Barros, Érica Amanda de; Broetto, Fernando; Bressan, Dayanne F.; Sartori, Maria M. P.; Costa, Vladimir E.

2014-05-01

Soybeans are an important food due to their functional and nutritional characteristics. However, consumption by western populations is limited by the astringent taste of soybeans and their derivatives which results from the action of lipoxygenase, an enzyme activated during product processing. The aim of this study was to evaluate the effect of gamma irradiation on the chemical composition and specific activity of lipoxygenase in different soybean cultivars. Soybeans were stored in plastic bags and irradiated with doses of 2.5, 5 and 10 kGy. The chemical composition (moisture, protein, lipids, ashes, crude fiber, and carbohydrates) and lipoxygenase specific activity were determined for each sample. Gamma irradiation induced a small increase of protein and lipid content in some soybean cultivars, which did not exceed the highest content of 5% and 26%, respectively, when compared to control. Lipoxygenase specific activity decreased in the three cultivars with increasing gamma irradiation dose. In conclusion, the gamma irradiation doses used are suitable to inactivate part of lipoxygenase while not causing expressive changes in the chemical composition of the cultivars studied.

Unraveling the Nature of Active Sites in Ethanol Electro-oxidation by Site-Specific Marking of a Pt Catalyst with Isotope-Labeled 13CO.

PubMed

Farias, Manuel J S; Cheuquepán, William; Tanaka, Auro A; Feliu, Juan M

2018-03-15

This works deals with the identification of preferential site-specific activation at a model Pt surface during a multiproduct reaction. The (110)-type steps of a Pt(332) surface were selectively marked by attaching isotope-labeled 13 CO molecules to them, and ethanol oxidation was probed by in situ Foureir transfrom infrared spectroscopy in order to precisely determine the specific sites at which CO 2 , acetic acid, and acetaldehyde were preferentially formed. The (110) steps were active for splitting the C-C bond, but unexpectedly, we provide evidence that the pathway of CO 2 formation was preferentially activated at (111) terraces, rather than at (110) steps. Acetaldehyde was formed at (111) terraces at potentials comparable to those for CO 2 formation also at (111) terraces, while the acetic acid formation pathway became active only when the (110) steps were released by the oxidation of adsorbed 13 CO, at potentials higher than for the formation of CO 2 at (111) terraces of the stepped surface.

Strong and multi-antigen specific immunity by hepatitis B core antigen (HBcAg)-based vaccines in a murine model of chronic hepatitis B: HBcAg is a candidate for a therapeutic vaccine against hepatitis B virus.

PubMed

Akbar, Sheikh Mohammad Fazle; Chen, Shiyi; Al-Mahtab, Mamun; Abe, Masanori; Hiasa, Yoichi; Onji, Morikazu

2012-10-01

Experimental evidence suggests that hepatitis B core antigen (HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with hepatitis B surface antigen (HBsAg)-based prophylactic vaccines with unsatisfactory clinical outcomes. In this study, we prepared HBsAg-pulsed dendritic cells (DC) and HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these antigens, which may serve as a better therapy for CHB. The kinetics of HBsAg, antibody levels against HBsAg (anti-HBs), proliferation of HBsAg- and HBcAg-specific lymphocytes, production of antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either HBsAg- or HBcAg-pulsed DC. Vaccination with HBsAg-pulsed DC induced HBsAg-specific immunity, but failed to induce HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with HBcAg-pulsed DC resulted in: (1) HBsAg negativity, (2) production of anti-HBs, and (3) development of HBsAg- and HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with HBcAg-pulsed DC compared to HBsAg-pulsed DC (p<0.05). The capacity of HBcAg to modulate both HBsAg- and HBcAg-specific immunity in HBV TM, and activation of endogenous DC in HBV TM without inducing liver damage suggests that HBcAg should be an integral component of the therapeutic vaccine against CHB. Copyright © 2012 Elsevier B.V. All rights reserved.

HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

PubMed

Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

2017-09-15

Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Validity of questions about activities of daily living to screen for dependency in older adults

PubMed Central

Rebouças, Monica; Coelho-Filho, João Macedo; Veras, Renato Peixoto; Lima-Costa, Maria Fernanda; Ramos, Luiz Roberto

2017-01-01

ABSTRACT OBJECTIVE To determine the criterion validity of the activities of daily living present in functionality questionnaires in older adults for population surveys and to identify which activities are valid to quantify the real daily need for help of this population. METHODS This is a population sample of older adults stratified by levels of functionality, according to self-perception of dependency in the activities of daily living. Self-perception was compared with the gold standard – direct observation of these activities in the household of older adults by a trained professional, blinded to the answers in the questionnaire. At the visit, it was decided if the older adult needed help to perform any of the activities of daily living for the research. The sensitivity of each activity of daily living was greater when the self-assessment that there was no need for help coincided with the assessment of the professional. Specificity indicates coincidence regarding the need for help in the activities of daily living – coefficients of sensitivity and specificity above 70% were considered as indicative of good validity. RESULTS Self-assessments showed better sensitivity than specificity – older adults and observers agreed more on daily independency than on dependency. All activities showed sensitivity above 70%. Some activities had low (go shopping: 55%) or very low specificity (brush the hair: 33%). The best specificities were to take a shower and dress up (95.8% for both), among the personal ones, and to use transportation and perform banking transactions (78% for both), among the instrumental ones. CONCLUSIONS Activities of daily living can be valid indicators of functional dependence. The best coefficients of validity were generally obtained for personal activities. Some activities with good sensitivities and specificities – walk 100 meters, take a shower, and lie down in and get out of the bed – can be used to classify older adults into low, average, and high need for help depending on the affected activities and, therefore, can help in the planning of health services aimed at them. PMID:28876414

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.

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.

Quantifying daily physical activity and determinants in sedentary patients with Parkinson's disease.

PubMed

Dontje, M L; de Greef, M H G; Speelman, A D; van Nimwegen, M; Krijnen, W P; Stolk, R P; Kamsma, Y P T; Bloem, B R; Munneke, M; van der Schans, C P

2013-10-01

Although physical activity is beneficial for Parkinson's disease (PD) patients, many do not meet the recommended levels. The range of physical activity among sedentary PD patients is unknown, as are factors that determine this variability. Hence, we aimed to (1) assess daily physical activity in self-identified sedentary PD patients; (2) compare this with criteria of a daily physical activity guideline; and (3) identify determinants of daily physical activity. Daily physical activity of 586 self-identified sedentary PD patients was measured with a tri-axial accelerometer for seven consecutive days. Physical fitness and demographic, disease-specific, and psychological characteristics were assessed. Daily physical activity was compared with the 30-min activity guideline. A linear mixed-effects model was estimated to identify determinants of daily physical activity. Accelerometer data of 467 patients who fulfilled all criteria revealed that >98% of their day was spent on sedentary to light-intensity activities. Eighty-two percent of the participants were 'physically inactive' (0 days/week of 30-min activity); 17% were 'semi-active' (1-4 days/week of 30-min activity). Age, gender, physical fitness, and scores on the Unified Parkinson's Disease Rating Scale explained 69% of the variability in daily physical activity. Performance-based measurements confirmed that most self-identified sedentary PD patients are 'physically inactive'. However, the variance in daily physical activity across subjects was considerable. Higher age, being female, and lower physical capacity were the most important determinants of reduced daily physical activity. Future therapeutic interventions should aim to improve daily physical activity in these high-risk patients, focusing specifically on modifiable risk factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action?

PubMed

Pereira, Maria G; Benevides, Norma M B; Melo, Marcia R S; Valente, Ana Paula; Melo, Fábio R; Mourão, Paulo A S

2005-09-05

Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors.

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.

Apoptosis as a post-phagocytic winnowing mechanism in a coral-dinoflagellate mutualism.

PubMed

Dunn, Simon R; Weis, Virginia M

2009-01-01

This study was aimed at detecting apoptosis as a post-phagocytic mechanism of symbiont selection during the onset of symbiosis in larvae of the scleractinian coral Fungia scutaria. Larvae were infected with one of three Symbiodinium types: freshly isolated homologous ITS-type C1f from adult F. scutaria, heterologous C31 from adult Montipora capitata, known to be unable to successfully colonize F. scutaria larvae, and type B1 from the symbiotic sea anemone Aiptasia spp. Apoptosis was detected by the activation of caspases, enzymes specific to apoptosis. Caspase activity was measured in situ by cleavage of a specific fluorophore and detection with confocal microscopy. At 6 h post infection, there was a significant increase in caspase activation in gastrodermal cells in C31-infected larvae, compared with larvae infected with C1f or B1 types. Compared with control larvae infected with C31, which had decreased infection rates present by 24 h post infection, when C31-infected larvae were incubated with a broad-scale caspase inhibitor, the per cent of larvae infected with C31 did not significantly decrease over time. This indicates that the reduction in infection success observed in untreated C31-infected larvae can be rescued with inhibition of caspases and apoptosis. This suggests the presence of a post-phagocytic recognition mechanism. Larvae infected with freshly isolated B1 retained infection success over time compared with C31-infected larvae, suggesting that there is host discrimination between heterologous algae. Initiation of this post-phagocytic response may occur more readily with a highly specific heterologous symbiont type such as C31, compared with a generalist heterologous type such as clade B1.

Jobs and Engines, Teacher's Guide: Political Issues. Comparing Political Experiences, Experimental Edition.

ERIC Educational Resources Information Center

Gillespie, Judith A.; Lazarus, Stuart

This teacher's guide to unit 5 of the 12th-grade second-semester "Comparing Political Experiences" course provides specific objectives and instructional procedures for each of the five activities that focus on the case study of the Cummins Engine Company. In addition, the guide provides instructions for coordinating the use of the…

Science through Engineering in Elementary School: Comparing Three Enactments of an Engineering-Design-Based Curriculum on the Science of Sound

ERIC Educational Resources Information Center

Wendell, Kristen Bethke

2011-01-01

This research illustrates how varying enactments of an engineering-design-based science curriculum shaped the development of students' domain-specific scientific ideas and practices. In this comparative case study rooted in the analytical perspectives of activity theory and learning environments, student and teacher participants in three…

Changes in Cortical Activity During Real and Imagined Movements: an ERP Study

PubMed Central

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E.

2013-01-01

This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions. PMID:24358049

Changes in Cortical Activity During Real and Imagined Movements: an ERP Study.

PubMed

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E

2013-11-15

This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions.

Diagnosis and characterization of mania: Quantifying increased energy and activity in the human behavioral pattern monitor.

PubMed

Perry, William; McIlwain, Meghan; Kloezeman, Karen; Henry, Brook L; Minassian, Arpi

2016-06-30

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Comprehensive Study of Formic Acid Oxidation on Palladium Nanocrystals with Different Types of Facets and Twin Defects

DOE PAGES

Choi, Sang-Il; Herron, Jeffrey A.; Scaranto, Jessica; ...

2015-04-13

Palladium has been recognized as the best anodic, monometallic electrocatalyst for the formic acid oxidation (FAO) reaction in a direct formic acid fuel cell. Here we report a systematic study of FAO on a variety of Pd nanocrystals, including cubes, right bipyramids, octahedra, tetrahedra, decahedra, and icosahedra. These nanocrystals were synthesized with approximately the same size, but different types of facets and twin defects on their surfaces. Our measurements indicate that the Pd nanocrystals enclosed by {100} facets have higher specific activities than those enclosed by {111} facets, in agreement with prior observations for Pd single-crystal substrates. If comparing nanocrystalsmore » predominantly enclosed by a specific type of facet, {100} or {111}, those with twin defects displayed greatly enhanced FAO activities compared to their single-crystal counterparts. To rationalize these experimental results, we performed periodic, self-consistent DFT calculations on model single-crystal substrates of Pd, representing the active sites present in the nanocrystals used in the experiments. The calculation results suggest that the enhancement of FAO activity on defect regions, represented by Pd(211) sites, compared to the activity of both Pd(100) and Pd(111) surfaces, could be attributed to an increased flux through the HCOO-mediated pathway rather than the COOH-mediated pathway on Pd(211). Since COOH has been identified as a precursor to CO, a site-poisoning species, a lower coverage of CO at the defect regions will lead to a higher activity for the corresponding nanocrystal catalysts, containing those defect regions.« less

The contribution of general and cancer-related variables in explaining physical activity in a breast cancer population 3 weeks to 6 months post-treatment.

PubMed

Charlier, Caroline; Van Hoof, Elke; Pauwels, Evelyn; Lechner, Lilian; Spittaels, Heleen; De Bourdeaudhuij, Ilse

2013-01-01

Physical activity determinants are subject to change when confronted with the diagnosis of 'cancer' and new cancer-related determinants appear. The aim of the present study is to compare the contribution of cancer-related determinants with more general ones in explaining physical activity 3 weeks to 6 months post-treatment. A theory-based and validated questionnaire was used to identify physical activity levels (total and domain-specific) and associated determinants among 464 breast cancer survivors (aged 18 to 65 years) 3 weeks to 6 months post-treatment. Descriptive analyses showed higher scores for general determinants in comparison with cancer-related determinants. Nevertheless, regression analyses showed that both general and cancer-related determinants explained total and domain-specific physical activity. Self-efficacy, enjoyment, social support, lack of time and lack of company were important general determinants. The perception of returning to normal life, cancer-related barriers (fatigue, lack of energy and physical side effects) and self-efficacy in overcoming these barriers were important cancer-related determinants. Although results differed according to the women's working status and the physical activity domain, general self-efficacy explained most physical activity types in both groups. Comparable with the general population, enhancing breast cancer survivors' self-efficacy in being sufficiently physically active seems to be important in physical activity interventions post-treatment. However, interventions should be tailored to the experienced symptoms and working status of the women. Copyright © 2011 John Wiley & Sons, Ltd.

Functional neuroimaging of sex differences in autobiographical memory recall.

PubMed

Young, Kymberly D; Bellgowan, Patrick S F; Bodurka, Jerzy; Drevets, Wayne C

2013-12-01

Autobiographical memory (AM) is episodic memory for personally experienced events. The brain areas underlying AM retrieval are known to include several prefrontal cortical and medial temporal lobe regions. Sex differences in AM recall have been reported in several behavioral studies, but the functional anatomical correlates underlying such differences remain unclear. This study used fMRI to compare the neural correlates of AM recall between healthy male and female participants (n = 20 per group). AM recall in response to positive, negative, and neutral cue words was compared to a semantic memory task involving the generation of examples from a category using emotionally valenced cues. Behaviorally, females recalled more negative and fewer positive AMs compared with males, while ratings of arousal, vividness, and memory age did not differ significantly between sexes. Males and females also did not differ significantly in their performance on control tasks. Neurophysiologically, females showed increased hemodynamic activity compared to males in the dorsolateral prefrontal cortex (DLPFC), dorsal anterior insula, and precuneus while recalling specific AMs (all valences combined); increased activity in the DLPFC, transverse temporal gyrus, and precuneus while recalling positive AMs; and increased activity in the anterior cingulate cortex, precuneus, amygdala, and temporopolar cortex when recalling negative AMs. When comparing positive to negative AMs directly, males and females differed in their BOLD responses in the hippocampus and DLPFC. We propose that the differential hemodynamic changes may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories. Copyright © 2012 Wiley Periodicals, Inc.

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.

Episodic specificity induction impacts activity in a core brain network during construction of imagined future experiences

PubMed Central

Madore, Kevin P.; Szpunar, Karl K.; Addis, Donna Rose; Schacter, Daniel L.

2016-01-01

Recent behavioral work suggests that an episodic specificity induction—brief training in recollecting the details of a past experience—enhances performance on subsequent tasks that rely on episodic retrieval, including imagining future experiences, solving open-ended problems, and thinking creatively. Despite these far-reaching behavioral effects, nothing is known about the neural processes impacted by an episodic specificity induction. Related neuroimaging work has linked episodic retrieval with a core network of brain regions that supports imagining future experiences. We tested the hypothesis that key structures in this network are influenced by the specificity induction. Participants received the specificity induction or one of two control inductions and then generated future events and semantic object comparisons during fMRI scanning. After receiving the specificity induction compared with the control, participants exhibited significantly more activity in several core network regions during the construction of imagined events over object comparisons, including the left anterior hippocampus, right inferior parietal lobule, right posterior cingulate cortex, and right ventral precuneus. Induction-related differences in the episodic detail of imagined events significantly modulated induction-related differences in the construction of imagined events in the left anterior hippocampus and right inferior parietal lobule. Resting-state functional connectivity analyses with hippocampal and inferior parietal lobule seed regions and the rest of the brain also revealed significantly stronger core network coupling following the specificity induction compared with the control. These findings provide evidence that an episodic specificity induction selectively targets episodic processes that are commonly linked to key core network regions, including the hippocampus. PMID:27601666

Effect of monophasic pulsed current on heel pain and functional activities caused by plantar fasciitis.

PubMed

Alotaibi, Abdullah K; Petrofsky, Jerrold S; Daher, Noha S; Lohman, Everett; Laymon, Michael; Syed, Hasan M

2015-03-20

Plantar fasciitis (PF) is a soft tissue disorder considered to be one of the most common causes of inferior heel pain. The aim of this study was to investigate the effect of monophasic pulsed current (MPC) and MPC coupled with plantar fascia-specific stretching exercises (SE) on the treatment of PF. Forty-four participants (22 women and 22 men, with a mean age of 49 years) diagnosed with PF were randomly assigned to receive MPC (n=22) or MPC coupled with plantar fascia-specific SE (n=22). Prior to and after 4 weeks of treatment, participants underwent baseline evaluation; heel pain was evaluated using a visual analogue scale (VAS), heel tenderness threshold was quantified using a handheld pressure algometer (PA), and functional activities level was assessed using the Activities of Daily Living subscale of the Foot and Ankle Ability Measure (ADL/FAAM). Heel pain scores showed a significant reduction in both groups compared to baseline VAS scores (P<0.001). Heel tenderness improved significantly in both groups compared with baseline PA scores (P<0.001). Functional activity level improved significantly in both groups compared with baseline (ADL/FAAM) scores (P<0.001). However, no significant differences existed between the 2 treatment groups in all post-intervention outcome measures. This trial showed that MPC is useful in treating inferior heel symptoms caused by PF.

Stability of local secondary structure determines selectivity of viral RNA chaperones.

PubMed

Bravo, Jack P K; Borodavka, Alexander; Barth, Anders; Calabrese, Antonio N; Mojzes, Peter; Cockburn, Joseph J B; Lamb, Don C; Tuma, Roman

2018-05-18

To maintain genome integrity, segmented double-stranded RNA viruses of the Reoviridae family must accurately select and package a complete set of up to a dozen distinct genomic RNAs. It is thought that the high fidelity segmented genome assembly involves multiple sequence-specific RNA-RNA interactions between single-stranded RNA segment precursors. These are mediated by virus-encoded non-structural proteins with RNA chaperone-like activities, such as rotavirus (RV) NSP2 and avian reovirus σNS. Here, we compared the abilities of NSP2 and σNS to mediate sequence-specific interactions between RV genomic segment precursors. Despite their similar activities, NSP2 successfully promotes inter-segment association, while σNS fails to do so. To understand the mechanisms underlying such selectivity in promoting inter-molecular duplex formation, we compared RNA-binding and helix-unwinding activities of both proteins. We demonstrate that octameric NSP2 binds structured RNAs with high affinity, resulting in efficient intramolecular RNA helix disruption. Hexameric σNS oligomerizes into an octamer that binds two RNAs, yet it exhibits only limited RNA-unwinding activity compared to NSP2. Thus, the formation of intersegment RNA-RNA interactions is governed by both helix-unwinding capacity of the chaperones and stability of RNA structure. We propose that this protein-mediated RNA selection mechanism may underpin the high fidelity assembly of multi-segmented RNA genomes in Reoviridae.

Effect of Monophasic Pulsed Current on Heel Pain and Functional Activities caused by Plantar Fasciitis

PubMed Central

Alotaibi, Abdullah K.; Petrofsky, Jerrold S.; Daher, Noha S.; Lohman, Everett; Laymon, Michael; Syed, Hasan M.

2015-01-01

Background Plantar fasciitis (PF) is a soft tissue disorder considered to be one of the most common causes of inferior heel pain. The aim of this study was to investigate the effect of monophasic pulsed current (MPC) and MPC coupled with plantar fascia-specific stretching exercises (SE) on the treatment of PF. Material/Methods Forty-four participants (22 women and 22 men, with a mean age of 49 years) diagnosed with PF were randomly assigned to receive MPC (n=22) or MPC coupled with plantar fascia-specific SE (n=22). Prior to and after 4 weeks of treatment, participants underwent baseline evaluation; heel pain was evaluated using a visual analogue scale (VAS), heel tenderness threshold was quantified using a handheld pressure algometer (PA), and functional activities level was assessed using the Activities of Daily Living subscale of the Foot and Ankle Ability Measure (ADL/FAAM). Results Heel pain scores showed a significant reduction in both groups compared to baseline VAS scores (P<0.001). Heel tenderness improved significantly in both groups compared with baseline PA scores (P<0.001). Functional activity level improved significantly in both groups compared with baseline (ADL/FAAM) scores (P<0.001). However, no significant differences existed between the 2 treatment groups in all post-intervention outcome measures. Conclusions This trial showed that MPC is useful in treating inferior heel symptoms caused by PF. PMID:25791231

Tracking Plasticity: Effects of Long-Term Rehearsal in Expert Dancers Encoding Music to Movement

PubMed Central

Bar, Rachel J.; DeSouza, Joseph F. X.

2016-01-01

Our knowledge of neural plasticity suggests that neural networks show adaptation to environmental and intrinsic change. In particular, studies investigating the neuroplastic changes associated with learning and practicing motor tasks have shown that practicing such tasks results in an increase in neural activation in several specific brain regions. However, studies comparing experts and non-experts suggest that experts employ less neuronal activation than non-experts when performing a familiar motor task. Here, we aimed to determine the long-term changes in neural networks associated with learning a new dance in professional ballet dancers over 34 weeks. Subjects visualized dance movements to music while undergoing fMRI scanning at four time points over 34-weeks. Results demonstrated that initial learning and performance at seven weeks led to increases in activation in cortical regions during visualization compared to the first week. However, at 34 weeks, the cortical networks showed reduced activation compared to week seven. Specifically, motor learning and performance over the 34 weeks showed the typical inverted-U-shaped function of learning. Further, our result demonstrate that learning of a motor sequence of dance movements to music in the real world can be visualized by expert dancers using fMRI and capture highly significant modeled fits of the brain network variance of BOLD signals from early learning to expert level performance. PMID:26824475

Isolating the effect of pore size distribution on electrochemical double-layer capacitance using activated fluid coke

NASA Astrophysics Data System (ADS)

Zuliani, Jocelyn E.; Tong, Shitang; Kirk, Donald W.; Jia, Charles Q.

2015-12-01

Electrochemical double-layer capacitors (EDLCs) use physical ion adsorption in the capacitive electrical double layer of high specific surface area (SSA) materials to store electrical energy. Previous work shows that the SSA-normalized capacitance increases when pore diameters are less than 1 nm. However, there still remains uncertainty about the charge storage mechanism since the enhanced SSA-normalized capacitance is not observed in all microporous materials. In previous studies, the total specific surface area and the chemical composition of the electrode materials were not controlled. The current work is the first reported study that systematically compares the performance of activated carbon prepared from the same raw material, with similar chemical composition and specific surface area, but different pore size distributions. Preparing samples with similar SSAs, but different pores sizes is not straightforward since increasing pore diameters results in decreasing the SSA. This study observes that the microporous activated carbon has a higher SSA-normalized capacitance, 14.1 μF cm-2, compared to the mesoporous material, 12.4 μF cm-2. However, this enhanced SSA-normalized capacitance is only observed above a threshold operating voltage. Therefore, it can be concluded that a minimum applied voltage is required to induce ion adsorption in these sub-nanometer micropores, which increases the capacitance.

Comparative evaluation of post-column free radical scavenging and ferric reducing antioxidant power assays for screening of antioxidants in strawberries.

PubMed

Raudonis, Raimondas; Raudone, Lina; Jakstas, Valdas; Janulis, Valdimaras

2012-04-13

ABTS and FRAP post-column techniques evaluate the antioxidant characteristics of HPLC separated compounds with specific reagents. ABTS characterize their ability to scavenge free radicals by electron-donating antioxidants, resulting in the absorbance decrease of the chromophoric radical. FRAP - is based on the reduction of Fe(III)-tripyridyltriazine complex to Fe(II)-tripyridyltriazine at low pH by electron-donating antioxidants, resulting in an absorbance increase. Both post-column assays were evaluated and compared according to the following validation parameters: specificity, precision, limit of detection (LoD), limit of quantitation (LoQ) and linearity. ABTS and FRAP post-column assays were specific, repeatable and sensitive and thus can be used for the evaluation of antioxidant active compounds. Antioxidant active compounds were quantified according to TEAC for each assay and ABTS/FRAP ratio was derived. No previous records of antioxidative activity of leaves and fruits of strawberries (Fragaria viridis, Fragaria moschata) research have been found. The research results confirm the reliability of ABTS and FRAP post-column assays for screening of antioxidants in complex mixtures and the determination of radical scavenging and ferric reducing ability by their TEAC values. Copyright © 2012 Elsevier B.V. All rights reserved.

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

In-shoe plantar pressure distribution and lower extremity muscle activity patterns of backward compared to forward running on a treadmill.

PubMed

Sterzing, Thorsten; Frommhold, Clivia; Rosenbaum, Dieter

2016-05-01

Backward locomotion in humans occurs during leisure, rehabilitation, and competitive sports. Little is known about its general biomechanical characteristics and how it affects lower extremity loading as well as muscle coordination. Thus, the purpose of this research was to analyze in-shoe plantar pressure patterns and lower extremity muscle activity patterns for backward compared to forward running. On a treadmill, nineteen runners performed forward running at their individually preferred speed, followed by backward running at 70% of their self-selected forward speed. In-shoe plantar pressures of nine foot regions and muscular activity of nine lower extremity muscles were recorded simultaneously over a one-minute interval. Backward and forward running variables were averaged over the accumulated steps and compared with Wilcoxon-signed rank tests (p<.05). For backward compared to forward running, in-shoe plantar pressure distribution showed a load increase under metatarsal heads I and II, as well as under the medial midfoot. This was indicated by higher maximum forces and peak pressures, and by longer contact times. Muscle activity showed significantly higher mean amplitudes during backward running in the semitendinosus, rectus femoris, vastus lateralis, and gluteus medius during stance, and in the rectus femoris during swing phase, while significantly lower mean amplitudes were observed in the tibialis anterior during swing phase. Observations indicate plantar foot loading and muscle activity characteristics that are specific for the running direction. Thus, backward running may be used on purpose for certain rehabilitation tasks, aiming to strengthen respective lower extremity muscles. Furthermore, the findings are relevant for sport specific backward locomotion training. Finally, results provide an initial baseline for innovative athletic footwear development aiming to increase comfort and performance during backward running. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

PubMed Central

Choi, Jung-Seok; Shin, Young-Chul; Jung, Wi Hoon; Jang, Joon Hwan; Kang, Do-Hyung; Choi, Chi-Hoon; Choi, Sam-Wook; Lee, Jun-Young; Hwang, Jae Yeon; Kwon, Jun Soo

2012-01-01

Background Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors. Methods/Principal Findings To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG. Conclusions Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation. PMID:23029329

Acceptance and commitment therapy - Do we know enough? Cumulative and sequential meta-analyses of randomized controlled trials.

PubMed

Hacker, Thomas; Stone, Paul; MacBeth, Angus

2016-01-15

Acceptance and Commitment Therapy (ACT) has accrued a substantial evidence base. Recent systematic and meta-analytic reviews suggest that ACT is effective compared to control conditions. However, these reviews appraise the efficacy of ACT across a broad range of presenting problems, rather than addressing specific common mental health difficulties. Focussing on depression and anxiety we performed a meta-analysis of trials of ACT. We incorporated sequential meta-analysis (SMA) techniques to critically appraise the sufficiency of the existing evidence base. Findings suggest that ACT demonstrates at least moderate group and pre-post effects for symptom reductions for both anxiety and depression. However using SMA findings are more qualified. There is currently insufficient evidence to confidently conclude that ACT for anxiety is efficacious when compared to active control conditions or as primary treatment for anxiety. Similarly, using SMA, there is currently insufficient evidence to suggest a moderate efficacy of ACT for depression compared to active control conditions. To stimulate further research we offer specific estimates of additional numbers of participants required to reach sufficiency to help inform future studies. We also discuss the appropriate strategies for future research into ACT for anxiety given the current evidence suggests no differential efficacy of ACT in the treatment of anxiety compared to active control conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Brozoski, Thomas J; Odintsov, Boris M; Faingold, Carl L

2017-09-01

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP. Copyright © 2017 Elsevier B.V. All rights reserved.

GC/MS analysis of high-performance liquid chromatography fractions from Sophora flavescens and Torilis japonica extracts and their in vitro anti-neosporal effects on Neospora caninum.

PubMed

Seo, Hun-Su; Kim, Kyoung Hee; Kim, Dae-Yong; Park, Bong-Kyun; Shin, Nam-Shik; Kim, Jae-Hoon; Youn, Heejeong

2013-01-01

We analyzed alcoholic extracts of herbs possessing anti-neosporal activity against Neospora (N.) caninum. To identify the chemical components of Sophora (S.) flavescens and Torilis (T.) japonica associated with anti-neosporal activity, specific fractions were isolated by high-performance liquid chromatography (HPLC). In vitro activity of the fractions against N. caninum was then assessed. Gas chromatography/ mass spectrometry (GC/MS) was used to identify and quantify specific anti-neosporal molecules in the herbal extracts. Almost all HPLC fractions of S. flavescens and T. japonica had higher levels of anti-neosporal activity compared to the not treated control. Active constituents of the extracts were sophoridane, furosardonin A, and tetraisopropylidene-cyclobutane in S. flavescens; 5,17-β-dihydroxy-de-A-estra-5,7,9,14-tetraene, furanodiene, and 9,12-octadecadienoic acid (Z,Z)-(CAS,1) in T. japonica.

GC/MS analysis of high-performance liquid chromatography fractions from Sophora flavescens and Torilis japonica extracts and their in vitro anti-neosporal effects on Neospora caninum

PubMed Central

Seo, Hun-Su; Kim, Kyoung Hee; Kim, Dae-Yong; Park, Bong-Kyun; Shin, Nam-Shik; Kim, Jae-Hoon

2013-01-01

We analyzed alcoholic extracts of herbs possessing anti-neosporal activity against Neospora (N.) caninum. To identify the chemical components of Sophora (S.) flavescens and Torilis (T.) japonica associated with anti-neosporal activity, specific fractions were isolated by high-performance liquid chromatography (HPLC). In vitro activity of the fractions against N. caninum was then assessed. Gas chromatography/mass spectrometry (GC/MS) was used to identify and quantify specific anti-neosporal molecules in the herbal extracts. Almost all HPLC fractions of S. flavescens and T. japonica had higher levels of anti-neosporal activity compared to the not treated control. Active constituents of the extracts were sophoridane, furosardonin A, and tetraisopropylidene-cyclobutane in S. flavescens; 5,17-β-dihydroxy-de-A-estra-5,7,9,14-tetraene, furanodiene, and 9,12-octadecadienoic acid (Z,Z)-(CAS,1) in T. japonica. PMID:23820198

Comparison of CT enterography and MR enterography imaging features of active Crohn disease in children and adolescents.

PubMed

Gale, Heather I; Sharatz, Steven M; Taphey, Mayureewan; Bradley, William F; Nimkin, Katherine; Gee, Michael S

2017-09-01

Assessment for active Crohn disease by CT enterography and MR enterography relies on identifying mural and perienteric imaging features. To evaluate the performance of established imaging features of active Crohn disease in children and adolescents on CT and MR enterography compared with histological reference. We included patients ages 18 years and younger who underwent either CT or MR enterography from 2007 to 2014 and had endoscopic biopsy within 28 days of imaging. Two pediatric radiologists blinded to the histological results reviewed imaging studies and scored the bowel for the presence or absence of mural features (wall thickening >3 mm, mural hyperenhancement) and perienteric features (mesenteric hypervascularity, edema, fibrofatty proliferation and lymphadenopathy) of active disease. We performed univariate analysis and multivariate logistic regression to compare imaging features with histological reference. We evaluated 452 bowel segments (135 from CT enterography, 317 from MR enterography) from 84 patients. Mural imaging features had the highest association with active inflammation both for MR enterography (wall thickening had 80% accuracy, 69% sensitivity and 91% specificity; mural hyperenhancement had 78%, 53% and 96%, respectively) and CT enterography (wall thickening had 84% accuracy, 72% sensitivity and 91% specificity; mural hyperenhancement had 76%, 51% and 91%, respectively), with perienteric imaging features performing significantly worse on MR enterography relative to CT enterography (P < 0.001). Mural features are predictors of active inflammation for both CT and MR enterography, while perienteric features can be distinguished better on CT enterography compared with MR enterography. This likely reflects the increased conspicuity of the mesentery on CT enterography and suggests that mural features are the most reliable imaging features of active Crohn disease in children and adolescents.

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia.

PubMed

Caminiti, Silvia P; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F

2015-01-01

bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.

Unfolding dimension and the search for functional markers in the human electroencephalogram

NASA Astrophysics Data System (ADS)

Dünki, Rudolf M.; Schmid, Gary Bruno

1998-02-01

A biparametric approach to dimensional analysis in terms of a so-called ``unfolding dimension'' is introduced to explore the extent to which the human EEG can be described by stable features characteristic of an individual despite the well-known problems of intraindividual variability. Our analysis comprises an EEG data set recorded from healthy individuals over a time span of 5 years. The outcome is shown to be comparable to advanced linear methods of spectral analysis with regard to intraindividual specificity and stability over time. Such linear methods have not yet proven to be specific to the EEG of different brain states. Thus we have also investigated the specificity of our biparametric approach by comparing the mental states schizophrenic psychosis and remission, i.e., illness versus full recovery. A difference between EEG in psychosis and remission became apparent within recordings taken at rest with eyes closed and no stimulated or requested mental activity. Hence our approach distinguishes these functional brain states even in the absence of an active or intentional stimulus. This sheds a different light upon theories of schizophrenia as an information-processing disturbance of the brain.

Pontin is required for pre-TCR signaling at the β-selection checkpoint in T cell development.

PubMed

Boo, Kyungjin; Baek, Sung Hee; Lee, Ho

2014-04-25

Pontin is a chromatin remodeling factor that possesses both ATPase and DNA helicase activities. Based on high expression in lymphoid tissues, we examined whether Pontin has a T cell-specific function. We generated Pontin(f/f);Lck-Cre mice, in which Pontin can be conditionally deleted in T cells and then explored T cell-specific function of Pontin in vivo. Here, we show that specific abrogation of Pontin expression in T cells almost completely blocked development of αβ T cells at the β-selection checkpoint by inducing cell apoptosis indicating that Pontin is essential for early T cell development. Pontin-deficient thymocytes show a comparable expression level of T cell receptor (TCR)β chain, but have enhanced activation of p53 and Notch signaling compared to wild-type thymocytes. Intriguingly, the developmental block of αβ T cells can be partially rescued by loss of p53. Together, our data demonstrate a novel role of Pontin as a crucial regulator in pre-TCR signaling during T cell development. Copyright © 2014 Elsevier Inc. All rights reserved.

The pathology and medicolegal aspects of sexual activity.

PubMed

Eckert, W G; Katchis, S; Donovan, W

1991-03-01

The pathology of injury and its complications related to sexual activities has changed remarkably when compared with that of the past, which usually involved assaults or murders of female victims of varying ages, with moderate to serve beatings that may have accidentally resulted in the victim's death. Serial murderers, serial rapists, and molesters of both boys and girls have become much more prevalent in the last two decades in the United States. Unorthodox sexual behavior, such as "fisting," has increased in frequency, as has sexual violence related to cults, such as satanism. All of these present many challenges to medicolegal investigators. This report describes general and specific pathological sexual activities and injuries, some characteristics and methods of the perpetrators, and some specific cases as examples.

Determination of strontium-90 in deer bones by liquid scintillation spectrometry after separation on Sr-specific ion exchange columns.

PubMed

Landstetter, Claudia; Wallner, Gabriele

2006-01-01

The activity concentration of (90)Sr was determined in several deer bones from Austria. Strontium specific ion exchange columns with 4',4''(5'')-di-t-butylcyclohexane-18-crown-6 from Eichrom Industries, Inc. were used for separation. The yield of the chemical procedure was quantified with AAS. Directly after column separation, the solution containing (90)Sr was mixed with the scintillation cocktail HiSafe III and measured by liquid scintillation counting. Prevention of (210)Pb contamination and reusability of the separation columns was investigated as well as the activity distribution within the bones. Results were compared with pre-Chernobyl measurements in Austria; a correlation between activity concentration of (90)Sr and site altitude was found.

Laminin promotes neuritic regeneration from cultured peripheral and central neurons

PubMed Central

1983-01-01

The ability of axons to grow through tissue in vivo during development or regeneration may be regulated by the availability of specific neurite-promoting macromolecules located within the extracellular matrix. We have used tissue culture methods to examine the relative ability of various extracellular matrix components to elicit neurite outgrowth from dissociated chick embryo parasympathetic (ciliary ganglion) neurons in serum-free monolayer culture. Purified laminin from both mouse and rat sources, as well as a partially purified polyornithine-binding neurite promoting factor (PNPF-1) from rat Schwannoma cells all stimulate neurite production from these neurons. Laminin and PNPF-1 are also potent stimulators of neurite growth from cultured neurons obtained from other peripheral as well as central neural tissues, specifically avian sympathetic and sensory ganglia and spinal cord, optic tectum, neural retina, and telencephalon, as well as from sensory ganglia of the neonatal mouse and hippocampal, septal, and striatal tissues of the fetal rat. A quantitative in vitro bioassay method using ciliary neurons was used to (a) measure and compare the specific neurite-promoting activities of these agents, (b) confirm that during the purification of laminin, the neurite-promoting activity co- purifies with the laminin protein, and (c) compare the influences of antilaminin antibodies on the neurite-promoting activity of laminin and PNPF-1. We conclude that laminin and PNPF-1 are distinct macromolecules capable of expressing their neurite-promoting activities even when presented in nanogram amounts. This neurite-promoting bioassay currently represents the most sensitive test for the biological activity of laminin. PMID:6643580

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

PubMed

Fusi, Jonathan; Bianchi, Sara; Daniele, Simona; Pellegrini, Silvia; Martini, Claudia; Galetta, Fabio; Giovannini, Luca; Franzoni, Ferdinando

2018-05-01

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

PubMed Central

Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

2016-01-01

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

PubMed

Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

2016-08-22

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. © 2016 Atapattu et al.

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…

Re-Thinking the "Thing" Sociomaterial Approaches to Understanding and Researching Learning in Work

ERIC Educational Resources Information Center

Fenwick, Tara

2010-01-01

Purpose: The purpose of this paper is to compare theoretical conceptions that reclaim and re-think material practice--"the thing" in the social and personal mix--specifically in terms of work activity and what is construed to be learning in that activity. Design/methodology/approach: The paper is theory-based. Three perspectives have been selected…

Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

PubMed

Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

2017-04-01

Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P 1 . In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys 55 and Lys 268 increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys 55 and Lys 268 with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa.

PubMed

Zeng, Huawei; Yan, Lin; Cheng, Wen-Hsing; Uthus, Eric O

2011-08-01

The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.

Extended cortical activations during evaluating successive pain stimuli.

PubMed

Lötsch, Jörn; Walter, Carmen; Felden, Lisa; Preibisch, Christine; Nöth, Ulrike; Martin, Till; Anti, Sandra; Deichmann, Ralf; Oertel, Bruno G

2012-08-01

Comparing pain is done in daily life and involves short-term memorizing and attention focusing. This event-related functional magnetic resonance imaging study investigated the short-term brain activations associated with the comparison of pain stimuli using a delayed discrimination paradigm. Fourteen healthy young volunteers compared two successive pain stimuli administered at a 10 s interval to the same location at the nasal mucosa. Fourteen age- and sex-matched subjects received similar pain stimuli without performing the comparison task. With the comparison task, the activations associated with the second pain stimulus were significantly greater than with the first stimulus in the anterior insular cortex and the primary somatosensory area. This was observed on the background of a generally increased stimulus-associated brain activation in the presence of the comparison task that included regions of the pain matrix (insular cortex, primary and secondary somatosensory area, midcingulate cortex, supplemental motor area) and regions associated with attention, decision making, working memory and body recognition (frontal and temporal gyri, inferior parietal lobule, precuneus, lingual cortices). This data provides a cerebral correlate for the role of pain as a biological alerting system that gains the subject's attention and then dominates most other perceptions and activities involving pain-specific and non-pain-specific brain regions.

Comparative biochemistry of renins and angiotensins in the vertebrates.

PubMed

Nakajima, T; Khosla, M C; Sakakibara, S

1978-09-01

Comparative biochemistry of renins and angiotensins was discussed. Renin extracted from hog kidney was different from that from mouse submaxillary glands in immunoreactivity and carbohydrate content. Rat kidney renin was also different from hog kidney renin in the amino acid composition. The presence of big and big-big renins was pointed out immunochemically. These big renins were considered to be precursors of kidney renin. Angiotensins in mammalian and nonmammalian species produced by renal or extrarenal renin have been differentiated by some biochemical and pharmacological criteria. Some of these angiotensins were analyzed sequentially. The replacements of amino acid residues at positions 1, 5, and/or 9 of angiotensin I have been demonstrated in nonmammalian species. Specific pressor activities have been determined using synthetic angiotensins by a 4 point assay in rat. Specific pressor activities of various angiotensins were obtained from the dose-blood pressure-response curves using a single angiotensin sample per assay rat.

Salivary exoglycosidases in gestational diabetes .

PubMed

Zalewska, Anna; Knaś, Małgorzata; Gumiężny, Grzegorz; Niczyporuk, Marek; Waszkiel, Danuta; Przystupa, Adrian Wojciech; Zarzycki, Wiesław

2013-04-19

As exoglycosidases have been described as potential markers of salivary gland pathology, we decided to check the possibility of the use of these enzymes in the detection of salivary gland involvement in gestational diabetes. For this purpose diabetic pregnant women were compared to pregnant and non-pregnant healthy women. The activities of total HEX as well as GLU in the saliva were determined in duplicate according to Marciniak et al. The activities of GAL, FUC, and MAN in the saliva were determined in duplicate according to Zwierz et al. It was found that the specific activities of exoglycosidases in the saliva of diabetic pregnant women significantly increased in comparison to healthy pregnant and non-pregnant women. Increased specific activity of exoglycosidases suggests that gestational diabetes provokes structural/functional alterations in salivary glands and changes in the salivary glycoconjugates metabolism.

Cryopreservation of Fish Sperm

NASA Astrophysics Data System (ADS)

Kurokura, Hisashi

Present status of research activities in cryopreservation of fish gamete in aquaculture field was introduced. More than 59 fish species have been reported in the research histories and nearly half of them were studied during recent 10 years. This means that the research activities are increasing, though commercial profit have not obtained yet. Fish species of which sperm can successfully cryopreserved is still limited comparing to numerous species in telost. One of the major obstacle for improvement of the technique is existence of wide specie specific variance in the freezing tolerance of fish sperm. The varianc can possibly be explaind thorugh the informations obtained by the studies in comparative spermatology, which is recently activated field in fish biology.

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

Analysis and optimization of the active rigidity joint

NASA Astrophysics Data System (ADS)

Manzo, Justin; Garcia, Ephrahim

2009-12-01

The active rigidity joint is a composite mechanism using shape memory alloy and shape memory polymer to create a passively rigid joint with thermally activated deflection. A new model for the active rigidity joint relaxes constraints of earlier methods and allows for more accurate deflection predictions compared to finite element results. Using an iterative process to determine the strain distribution and deflection, the method demonstrates accurate results for both surface bonded and embedded actuators with and without external loading. Deflection capabilities are explored through simulated annealing heuristic optimization using a variety of cost functions to explore actuator performance. A family of responses presents actuator characteristics in terms of load bearing and deflection capabilities given material and thermal constraints. Optimization greatly expands the available workspace of the active rigidity joint from the initial configuration, demonstrating specific work capabilities comparable to those of muscle tissue.

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.

Two classes of receptor specific for sperm-activating peptide III in sand-dollar spermatozoa.

PubMed

Yoshino, K; Suzuki, N

1992-06-15

We characterized receptors specific for sperm-activating peptide III (SAP-III: DSDSAQNLIQ) in spermatozoa of the sand dollar, Clypeaster japonicus, using both binding and cross-linking techniques. Analyses of the data obtained from the equilibrium binding of a radiolabeled SAP-III analogueto C. japonicus spermatozoa, using Klotz, Scatchard and Hill plots, showed the presence of two classes of receptors specific for SAP-III in the spermatozoa. One of the receptors (high-affinity) had a Kd of 3.4 nM and 3.4 x 10(4) binding sites/spermatozoon. The other receptor (low-affinity) had a Kd of 48 nM, with 6.1 x 10(4) binding sites/spermatozoon. The Kd of the high-affinity receptor was comparable to the median effective concentration of the intracellular-pH-increasing activity of SAP-III and that of the low-affinity receptor was comparable to the median effective concentration of the cellular-cGMP-elevating activity of the peptide. In addition, Scatchard and Hill plots of the data suggested the existence of positive cooperativity between the high-affinity members. Similar results were also obtained from a binding experiment using a sperm-membrane fraction prepared from C. japonicus spermatozoa. The incubation of intact spermatozoa or sperm plasma membranes with the radioiodinated SAP-III analogue and a chemical cross-linking reagent, disuccinimidyl suberate, resulted in the radiolabeling of three proteins with molecular masses of 126, 87 and 64 kDa, estimated by SDS/PAGE under reducing conditions.

Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for Broccoli By-Product Utilization.

PubMed

Liu, Mengpei; Zhang, Lihua; Ser, Suk Lan; Cumming, Jonathan R; Ku, Kang-Mo

2018-04-13

The phytonutrient concentrations of broccoli ( Brassica oleracea var. italica) florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids, chlorophylls, vitamins E and K, essential mineral elements, total phenolic content, antioxidant activity, and expression of glucosinolate biosynthesis and hydrolysis genes were quantified from the different broccoli tissues. Broccoli florets had higher concentrations of amino acids, glucoraphanin, and neoglucobrassicin compared to other tissues, whereas leaves were higher in carotenoids, chlorophylls, vitamins E and K, total phenolic content, and antioxidant activity. Leaves were also good sources of calcium and manganese compared to other tissues. Stems had the lowest nitrile formation from glucosinolate. Each tissue exhibited specific core gene expression profiles supporting glucosinolate metabolism, with different gene homologs expressed in florets, stems, and leaves, which suggests that tissue-specific pathways function to support primary and secondary metabolic pathways in broccoli. This comprehensive nutrient and bioactive compound profile represents a useful resource for the evaluation of broccoli by-product utilization in the human diet, and as feedstocks for bioactive compounds for industry.

RNaseI from Escherichia coli cannot substitute for S-RNase in rejection of Nicotiana plumbaginifolia pollen.

PubMed

Beecher, B; Murfett, J; McClure, B A

1998-03-01

Unilateral incompatibility often occurs between self-incompatible (SI) species and their self-compatible (SC) relatives. For example, SI Nicotiana alata rejects pollen from SC N. plumbaginifolia, but the reciprocal pollination is compatible. This interspecific pollen rejection system closely resembles intraspecific S-allele-specific pollen rejection. However, the two systems differ in degree of specificity. In SI, rejection is S-allele-specific, meaning that only a single S-RNase causes rejection of pollen with a specific S genotype. Rejection of N. plumbaginifolia pollen is less specific, occurring in response to almost any S-RNase. Here, we have tested whether a non-S-RNase can cause rejection of N. plumbaginifolia pollen. The Escherichia coli rna gene encoding RNAseI was engineered for expression in transgenic (N. plumbaginifolia x SC N. alata) hybrids. Expression levels and pollination behavior of hybrids expressing E. coli RNaseI were compared to controls expressing SA2-RNase from N. alata. Immunoblot analysis and RNase activity assays showed that RNaseI and SA2-RNase were expressed at comparable levels. However, expression of SA2-RNase caused rejection of N. plumbaginifolia pollen, whereas expression of RNaseI did not. Thus, in this system, RNase activity alone is not sufficient for rejection of N. plumbaginifolia pollen. The results suggest that S-RNases may be specially adapted to function in pollen rejection.

Mechanisms and neural basis of object and pattern recognition: a study with chess experts.

PubMed

Bilalić, Merim; Langner, Robert; Erb, Michael; Grodd, Wolfgang

2010-11-01

Comparing experts with novices offers unique insights into the functioning of cognition, based on the maximization of individual differences. Here we used this expertise approach to disentangle the mechanisms and neural basis behind two processes that contribute to everyday expertise: object and pattern recognition. We compared chess experts and novices performing chess-related and -unrelated (visual) search tasks. As expected, the superiority of experts was limited to the chess-specific task, as there were no differences in a control task that used the same chess stimuli but did not require chess-specific recognition. The analysis of eye movements showed that experts immediately and exclusively focused on the relevant aspects in the chess task, whereas novices also examined irrelevant aspects. With random chess positions, when pattern knowledge could not be used to guide perception, experts nevertheless maintained an advantage. Experts' superior domain-specific parafoveal vision, a consequence of their knowledge about individual domain-specific symbols, enabled improved object recognition. Functional magnetic resonance imaging corroborated this differentiation between object and pattern recognition and showed that chess-specific object recognition was accompanied by bilateral activation of the occipitotemporal junction, whereas chess-specific pattern recognition was related to bilateral activations in the middle part of the collateral sulci. Using the expertise approach together with carefully chosen controls and multiple dependent measures, we identified object and pattern recognition as two essential cognitive processes in expert visual cognition, which may also help to explain the mechanisms of everyday perception.

Pharmaceutical quality of generic isotretinoin products, compared with Roaccutane.

PubMed

Taylor, Peter W; Keenan, Michael H J

2006-03-01

Isotretinoin is the drug of choice for the management of severe recalcitrant nodular acne. Several generic products are available. However, their pharmaceutical quality, in particular particle size distribution, which may affect safety and efficacy is unknown. Hence, prescribing of some generic products may be problematic. To assess the pharmaceutical quality of 14 generic isotretinoin products compared with Roaccutane (F. Hoffmann-La Roche Ltd). Tests were performed according to Roche standard procedures, European and US pharmacopoeia specifications. Tests included isotretinoin content, identity and amount of impurities and degradation products, effect of accelerated shelf-life studies on stability, particle size distribution and composition of non-active ingredients. The 14 isotretinoin products differed by 30-fold in median particle size and showed variation in their non-active ingredients. The average isotretinoin content of Acnotin and Acne-Tretin fell outside the 95-105% Roche specifications. Following accelerated shelf-life tests, only four products retained isotretinoin content within Roche specifications, whilst Acne-Tretin (the only powder formulation) lost 72.5% isotretinoin content. Two generic products exceeded the +/- 2% specification (Ph. Eur.) and a further three exceeded the +/- 1% (USP) for tretinoin content, eight exceeded the 2.54% specification for total impurities and six contained >or= 5 unknown impurities. Isotretinoin-5.6-epoxide content exceeded the 1.04% specification in five generic products. Thirteen generic products failed to match Roaccutane in one or more tests and 11 failed in three or more tests. It cannot be assumed that all generic isotretinoin products are as therapeutically effective or safe as Roaccutane.

A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease.

PubMed

Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D'Addato, Sergio; Tozzi, Giulia; D'Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi

2017-05-25

Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

Electrophysiological characteristics of task-specific tremor in 22 instrumentalists.

PubMed

Lee, André; Tominaga, Kenta; Furuya, Shinichi; Miyazaki, Fumio; Altenmüller, Eckart

2015-03-01

Our aim was to address three characteristics of task-specific tremor in musicians (TSTM): First, we quantified muscular activity of flexor and extensor muscles, of coactivation as well as tremor acceleration. Second, we compared muscular activity between task-dependent and position-dependent tremor. Third, we investigated, whether there is an overflow of muscular activity to muscles adjacent to the affected muscles in TSTM. Tremor acceleration and muscular activity were measured in the affected muscles and the muscles adjacent to the affected muscles in 22 patients aged 51.5 ± 11.4 years with a task-specific tremor. We assessed power of muscular oscillatory activity and calculated the coherence between EMG activity of affected muscles and tremor acceleration as well as between adjacent muscles and tremor acceleration. This was done for task-dependent and position-dependent tremor. We found the highest power and coherence of muscular oscillatory activity in the frequency range of 3-8 Hz for affected and adjacent muscles. No difference was found between task-dependent and position-dependent tremor in neither power nor coherence measures. Our results generalize previous results of a relation between coactivation and tremor among a variety of musicians. Furthermore, we found coherence of adjacent muscles and TSTM. This indicates that overflow exists in TSTM and suggests an association of TST with dystonia.

Initial and sustained brain responses to threat anticipation in blood-injection-injury phobia.

PubMed

Brinkmann, Leonie; Poller, Hendrik; Herrmann, Martin J; Miltner, Wolfgang; Straube, Thomas

2017-01-01

Blood-injection-injury (BII) phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC), insula, lateral and medial prefrontal cortex (PFC), thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion.

Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia.

PubMed

Saito, Kosuke; Moore, Rick; Negishi, Masahiko

2013-03-01

KCNK1, a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after phenobarbital treatment. Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital-inducible antihyperplasia factor. Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter. This binding is observed in the livers of male mice, but not in the livers of female mice and requires the pituitary gland, because hypophysectomy abrogates it. Hyperplasia further progressed in the livers of Kcnk1 ( -/- ) male mice compared with those of Kcnk1 ( +/+ ) males after phenobarbital treatment. Thus, KCNK1 suppresses phenobarbital-induced hyperplasia. These results indicate that phenobarbital treatment induces KCNK1 to elicit a male-specific and growth-suppressing signal. Thus, KCNK1 and Kcnk1 ( -/- ) mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice.

Physical Activity Patterns Among Older Adults With and Without Knee Osteoarthritis in Six European Countries.

PubMed

Herbolsheimer, Florian; Schaap, Laura A; Edwards, Mark H; Maggi, Stefania; Otero, Ángel; Timmermans, Erik J; Denkinger, Michael D; van der Pas, Suzan; Dekker, Joost; Cooper, Cyrus; Dennison, Elaine M; van Schoor, Natasja M; Peter, Richard

2016-02-01

To investigate patterns of physical activity in older adults with knee osteoarthritis (OA) compared to older adults without knee OA across 6 European countries. We expect country-specific differences in the physical activity levels between persons with knee OA compared to persons without knee OA. A varying degree of physical activity levels across countries would express a facilitating or impeding influence of the social, environmental, and other contextual factors on a physically active lifestyle. Baseline cross-sectional data from the European Project on Osteoarthritis were analyzed. In total, 2,551 participants from 6 European countries (Germany, Italy, The Netherlands, Spain, Sweden, and the UK) were included. Participants with knee OA were less likely to follow physical activity recommendations and had poorer overall physical activity profiles than those without knee OA (mean 62.9 versus 81.5 minutes/day, respectively; P = 0.015). The magnitude of this difference varied across countries. Detailed analysis showed that low physical activity levels in persons with knee OA could be attributed to less everyday walking time (odds ratio 1.31, 95% confidence interval 1.07-1.62). This study highlighted the fact that having knee OA is associated with a varying degree of physical activity patterns in different countries. This national variation implies that low levels of physical activity among persons with knee OA cannot be explained exclusively by individual or disease-specific factors, but that social, environmental, and other contextual factors should also be taken into account. © 2016, American College of Rheumatology.

Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.

PubMed

Uchida, Yoko; Irie, Koichiro; Fukuhara, Daiki; Kataoka, Kota; Hattori, Takako; Ono, Mitsuaki; Ekuni, Daisuke; Kubota, Satoshi; Morita, Manabu

2018-06-23

Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin , which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II , and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1 . In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.

Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder

PubMed Central

Britton, Jennifer C.; Stewart, S. Evelyn; Killgore, William D.S.; Rosso, Isabelle M.; Price, Lauren M.; Gold, Andrea L.; Pine, Daniel S.; Wilhelm, Sabine; Jenike, Michael A.; Rauch, Scott L.

2010-01-01

Background Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation (Cannistraro et al., 2004). Methods In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a healthy comparison sample (HC, N=17) performed a gender discrimination task while viewing emotional faces (happy, fear, disgust) and neutral faces. Results Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. Conclusions Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder-specific. PMID:20602430

Controlled ecological evaluation of an implemented exercise training programme to prevent lower limb injuries in sport: differences in implementation activity.

PubMed

Donaldson, Alex; Gabbe, Belinda J; Lloyd, David G; Cook, Jill; Finch, Caroline F

2018-04-24

The public health benefits of injury prevention programmes are maximised when programmes are widely adopted and adhered to. Therefore, these programmes require appropriate implementation support. This study evaluated implementation activity outcomes associated with the implementation of FootyFirst, an exercise training injury prevention programme for community Australian football, both with (FootyFirst+S) and without (FootyFirst+NS) implementation support. An evaluation plan based on the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) Sports Setting Matrix was applied in a controlled ecological evaluation of the implementation of FootyFirst. RE-AIM dimension-specific (range: 0-2) and total RE-AIM scores (range: 0-10) were derived by triangulating data from a number of sources (including surveys, interviews, direct observations and notes) describing FootyFirst implementation activities. The mean dimension-specific and total scores were compared for clubs in regions receiving FootyFirst+S and FootyFirst+NS, through analysis of variance. The mean total RE-AIM score forclubs in the FootyFirst+S regions was 2.4 times higher than for clubs in the FootyFirst+NS region (4.73 vs 1.94; 95% CI for the difference: 1.64 to 3.74). Similarly, all dimension-specific scores were significantly higher for clubs in the FootyFirst+S regions compared with clubs in the FootyFirst+NS region. In all regions, the dimension-specific scores were highest for reach and adoption, and lowest for implementation. Implementing exercise training injury prevention programmes in community sport is challenging. Delivering programme content supported by a context-specific and evidence-informed implementation plan leads to greater implementation activity, which is an important precursor to injury reductions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Prey specificity, comparative lethality and compositional differences of coral snake venoms.

PubMed

Jorge da Silva, N; Aird, S D

2001-03-01

Toxicities of crude venoms from 49 coral snake (Micrurus sp.) populations, representing 15 nominal taxa, were examined in both laboratory mice and in native prey animals and compared with data gathered from two non-micrurine elapids and a crotalid, which served as outgroups. These venoms were further compared on the basis of 23 enzymatic activities. Both toxicities and enzymatic activities were analyzed with respect to natural prey preferences, as determined from stomach content analyses and literature reports. Venoms of nearly all Micrurus for which prey preferences are known, are more toxic to natural prey than to non-prey species. Except for amphisbaenians, prey are more susceptible to venoms of Micrurus that feed upon them, than to venoms of those that eat other organisms. All venoms were more toxic i.v.>i.p.>i.m. Route-specific differences in toxicity are generally greatest for preferred prey species. Cluster analyses of venom enzymatic activities resulted in five clusters, with the fish-eating M. surinamensis more distant from other Micrurus than even the crotalid, Bothrops moojeni. Ophiophagous and amphisbaenian-eating Micrurus formed two close subclusters, one allied to the outgroup species Naja naja and the other to the fossorial, ophiophagous Bungarus multicinctus. Prey preference is shown to be the most important determinant of venom composition in Micrurus.

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 lymphoproliferative response to enzymatically digested gelatin in subjects with gelatin hypersensitivity.

PubMed

Kumagai, T; Nakayama, T; Kamada, M; Igarashi, C; Yuri, K; Furukawa, H; Wagatuma, K; Tsutsumi, H; Chiba, S; Kojima, H; Saito, A; Okui, T; Yano, S

2000-10-01

This study was designed to evaluate the immunogenic characteristics of enzymatically digested gelatin, 'FreAlagin', employing the lymphoproliferative response in subjects with gelatin hypersensitivity. Our purpose was to assess the response of primed lymphocytes to the newly developed FreAlagin and compare it to the response to conventional gelatin. A gelatin-specific lymphocyte proliferation test (LPT) was performed in 110 children with adverse reactions to gelatin-containing vaccines, who showed positive gelatin-specific cell-mediated immunity and were thus diagnosed as having gelatin hypersensitivity. Gelatin-specific IgE was measured in all subjects. The antigenic activity of FreAlagin to lymphocytes was compared with that of conventional bovine gelatin. Positive and negative control specimens were obtained from the patients with anaphylaxis and from subjects inoculated with gelatin-free vaccine who showed no adverse reactions in order to establish the fluorometric ELISA system to determine IgE antibody to gelatin and LPT. The lymphocyte activity against FreAlagin was much less than that to Wako gelatin and more than half of the subjects who reacted positively to Wako gelatin had a negative LPT to FreAlagin. Although 47% of the subjects had positive LPTs to FreAlagin, all but two still had lower SIs to FreAlagin compared with Wako gelatin. We conclude that the antigenic activity of FreAlagin as measured by the cell-mediated immune response is significantly less than that of conventional bovine gelatin. However, it is still necessary to perform clinical trials to show a reduced or absent clinical reactivity to FreAlagin in sensitized patients to conventional gelatin.

The insula is not specifically involved in disgust processing: an fMRI study.

PubMed

Schienle, A; Stark, R; Walter, B; Blecker, C; Ott, U; Kirsch, P; Sammer, G; Vaitl, D

2002-11-15

fMRI studies have shown that the perception of facial disgust expressions specifically activates the insula. The present fMRI study investigated whether this structure is also involved in the processing of visual stimuli depicting non-mimic disgust elicitors compared to fear-inducing and neutral scenes. Twelve female subjects were scanned while viewing alternating blocks of 40 disgust-inducing, 40 fear-inducing and 40 affectively neutral pictures, shown for 1.5 s each. Afterwards, affective ratings were assessed. The disgust pictures, rated as highly repulsive, induced activation in the insula, the amygdala, the orbitofrontal and occipito-temporal cortex. Since during the fear condition the insula was also involved, our findings do not fit the idea of the insula as a specific disgust processor.

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.

Rapid detection of urinary soluble intercellular adhesion molecule-1 for determination of lupus nephritis activity.

PubMed

Wang, Yanyun; Tao, Ye; Liu, Yi; Zhao, Yi; Song, Chao; Zhou, Bin; Wang, Tao; Gao, Linbo; Zhang, Lin; Hu, Huaizhong

2018-06-01

The current methods of monitoring the activity of lupus nephritis (LN) may cause unnecessary hospital visits or delayed immunosuppressive therapy. We aimed to find a urinary biomarker that could be developed as a home-based test for monitoring the activity of LN.Urine samples were collected immediately before a renal biopsy from patients of suspected active LN, and also from patients with inactive LN, systemic lupus erythematous without LN or healthy controls. Biomarker search was conducted on a cytokine antibody array and confirmation was done by quantitative evaluation with enzyme-linked immunosorbent assay. The Mann-Whiney test or Student t test was used to compare the levels of 9 cytokines between different groups. The sensitivity and specificity of each cytokine for diagnosis of LN was evaluated by receiver operating characteristic curve. A rapid test based on colloidal gold immunochromatography was then developed for bedside or home use. Furthermore, an experimental e-healthcare system was constructed for recording and sharing the results of the rapid test a cloud-assisted internet of things (IoT) consisting of a sensing device, an IoT device and a cloud server.Adiponectin (Acrp30), soluble intercellular cell adhesion molecule-1 (sICAM-1), neural cell adhesion molecule 1 (NCAM-1), and CD26 were significantly higher in urine samples of active LN patients. sICAM-1 appeared more sensitive and specific among these candidates. When the cut-off value of sICAM-1 was set at 1.44 ng/mL, the sensitivity reached 98.33% with a specificity at 85.71%. The sICAM-1 strip test showed comparable sensitivity of 95% and a specificity of 83.3% for assessing the LN activity. Meanwhile, the e-healthcare system was able to conveniently digitize and share the sICAM-1 rapid test results.sICAM-1 appeared to be an excellent biomarker for monitoring LN activity. The e-healthcare system with cloud-assisted IoT could assist the digitalization and sharing of the bedside or home-based sICAM-1 test results.

Modulation of Cardiac Ryanodine Receptor Channels by Alkaline Earth Cations

PubMed Central

Diaz-Sylvester, Paula L.; Porta, Maura; Copello, Julio A.

2011-01-01

Cardiac ryanodine receptor (RyR2) function is modulated by Ca2+ and Mg2+. To better characterize Ca2+ and Mg2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M2+: Mg2+, Ca2+, Sr2+, Ba2+) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca2+ or Sr2+. This activation was interfered by Mg2+ and Ba2+ acting at low affinity M2+-unspecific binding sites. When testing the effects of luminal M2+ as current carriers, all M2+ increased maximal RyR2 open probability (compared to Cs+), suggesting the existence of low affinity activating M2+-unspecific sites at the luminal surface. Responses to M2+ vary from channel to channel (heterogeneity). However, with luminal Ba2+or Mg2+, RyR2 were less sensitive to cytosolic Ca2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca2+or Sr2+). Kinetics of RyR2 with mixtures of luminal Ba2+/Ca2+ and additive action of luminal plus cytosolic Ba2+ or Mg2+ suggest luminal M2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca2+/Sr2+-specific sites, which stabilize high Po mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M2+ binding sites (specific for Ca2+ and unspecific for Ca2+/Mg2+) that dynamically modulate channel activity and gating status, depending on SR voltage. PMID:22039534

B29 Gene Silencing in Pituitary Cells is Regulated by Its 3′ Enhancer

PubMed Central

Malone, Cindy S.; Kuraishy, Ali I.; Fike, Francesca M.; Loya, Ruchika G.; Mikkili, Minil R.; Teitell, Michael A.; Wall, Randolph

2007-01-01

Summary B cell-specific B29 (Igβ, CD79b) genes in rat, mouse, and human are situated between the 5′ growth hormone (GH) locus control region (LCR) and the 3′ GH gene cluster. The entire GH genomic region is DNase1 hypersensitive in GH-expressing pituitary cells, which predicts an “open” chromatin configuration, and yet B29 is not expressed. The B29 promoter and enhancers exhibit histone deacetylation in pituitary cells, but histone deacetylase inhibition failed to activate B29 expression. The B29 promoter and a 3′ enhancer showed local dense DNA methylation in both pituitary and non-lymphoid cells consistent with gene silencing. However, DNA methyltransferase inhibition did not activate B29 expression either. B29 promoter constructs were minimally activated in transfected pituitary cells. Co-transfection of the B cell-specific octamer transcriptional co-activator Bob1 with the B29 promoter construct resulted in high level promoter activity in pituitary cells comparable to B29 promoter activity in transfected B cells. Unexpectedly, inclusion of the B29 3′ enhancer in B29 promoter constructs strongly inhibited B29 transcriptional activity even when pituitary cells were co-transfected with Bob1. Both Oct-1 and Pit-1 bind the B29 3′ enhancer in in vitro EMSA and in in vivo chromatin immunoprecipitation analyses. These data indicate that the GH locus-embedded, tissue-specific B29 gene is silenced in GH-expressing pituitary cells by epigenetic mechanisms, the lack of a B cell-specific transcription factor, and likely by the B29 3′ enhancer acting as a powerful silencer in a context and tissue-specific manner. PMID:16920149

Modification of the hTERT promoter by heat shock elements enhances the efficiency and specificity of cancer targeted gene therapy.

PubMed

Wang, Xiaolong; Zhou, PeiHua; Sun, XueJun; Wei, GuangBing; Zhang, Li; Wang, Hui; Yao, JianFeng; Jia, PengBo; Zheng, JianBao

2016-05-01

One of the current challenges facing cancer gene therapy is the tumour-specific targeting of therapeutic genes. Effective targeting in gene therapy requires accurate spatial and temporal control of gene expression. To develop a sufficient and accurate tumour-targeting method for cancer gene therapy, we have investigated the use of hyperthermia to control the expression of a transgene under the control of the human telomerase reverse transcriptase (hTERT) promoter and eight heat shock elements (8HSEs). Luciferase reporters were constructed by inserting eight HSEs and the hTERT promoter (8HSEs-hTERTp) upstream of the pGL4.20 vector luciferase gene. The luciferase activity of the hTERT promoter and 8HSEs-hTERT promoter were then compared in the presence and absence of heat. The differences in luciferase activity were analysed using dual luciferase assays in SW480 (high hTERT expression), MKN28 and MRC-5 cells (low hTERT expression). The luciferase activity of the Hsp70B promoter was also compared to the 8HSEs-hTERT promoter in the above listed cell lines. Lentiviral vector and heat-induced expression of EGFP expression under the control of the 8HSEs-hTERT promoter in cultured cells and mouse tumour xenografts was measured by reverse transcription polymerase (RT-PCR), Western blot and immunofluorescence assays. hTERT promoter activity was higher in SW480 cells than in MKN28 or MRC-5 cells. At 43 °C, the luciferase activity of the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN28 or MRC-5 cells. Importantly, the differences in luciferase activity were much more obvious in both high (SW480) and low (MKN28 and MRC-5) hTERT expressing cells when the activity of the 8HSEs-hTERT promoter was compared to the Hsp70B promoter. Moreover, under the control of 8HSEs-hTERT promoter in vitro and in vivo, EGFP expression was obviously increased by heat treatment in SW480 cells but not in MKN28 or MRC-5 cells, nor was expression increased under normal temperature conditions. The hTERT promoter is a potentially powerful tumour-specific promoter and gene therapy tool for cancer treatment. Incorporating heat-inducible therapeutic elements (8HSEs) into the hTERT promoter may enhance the efficiency and specificity of cancer targeting gene therapy under hyperthermic clinical conditions.

Parietal Activation During Retrieval of Abstract and Concrete Auditory Information

PubMed Central

Klostermann, Ellen C.; Kane, Ari J.M.; Shimamura, Arthur P.

2008-01-01

Successful memory retrieval has been associated with a neural circuit that involves prefrontal, precuneus, and posterior parietal regions. Specifically, these regions are active during recognition memory tests when items correctly identified as “old” are compared with items correctly identified as “new.” Yet, as nearly all previous fMRI studies have used visual stimuli, it is unclear whether activations in posterior regions are specifically associated with memory retrieval or if they reflect visuospatial processing. We focus on the status of parietal activations during recognition performance by testing memory for abstract and concrete nouns presented in the auditory modality with eyes closed. Successful retrieval of both concrete and abstract words was associated with increased activation in left inferior parietal regions (BA 40), similar to those observed with visual stimuli. These results demonstrate that activations in the posterior parietal cortex during retrieval cannot be attributed to bottom-up visuospatial processes but instead have a more direct relationship to memory retrieval processes. PMID:18243736

Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

PubMed

Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

2017-05-19

The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control.

PubMed

Rodrigue, Amanda L; Schaeffer, David J; Pierce, Jordan E; Clementz, Brett A; McDowell, Jennifer E

2018-01-01

Cognitive control impairments in schizophrenia (SZ) can be evaluated using antisaccade tasks and functional magnetic resonance imaging (fMRI). Studies, however, often compare people with SZ to high performing healthy people, making it unclear if antisaccade-related disruptions are specific to the disease or due to generalized deficits in cognitive control. We included two healthy comparison groups in addition to people with SZ: healthy people with high cognitive control (HCC), who represent a more typical comparison group, and healthy people with low cognitive control (LCC), who perform similarly on antisaccade measures as people with SZ. Using two healthy comparison groups may help determine which antisaccade-related deficits are specific to SZ (distinguish SZ from LCC and HCC groups) and which are due to poor cognitive control (distinguish the LCC and SZ groups from the HCC group). People with SZ and healthy people with HCC or LCC performed an antisaccade task during fMRI acquisition. LCC and SZ groups showed under-activation of saccade circuitry. SZ-specific disruptions were observed in the left superior temporal gyrus and insula during error trials (suppression of activation in the SZ group compared to the LCC and HCC group). Differences related to antisaccade errors may distinguish people with SZ from healthy people with LCC.

The angle-torque-relationship of the subtalar pronators and supinators in male athletes: A comparative study of soccer and handball players.

PubMed

Hagen, Marco; Asholt, Johannes; Lemke, Martin; Lahner, Matthias

2016-05-18

It is currently unclear how participation in different sports affects the angle-specific subtalar pronator and supinator muscle strength and pronator-to-supinator strength ratio (PSR). Based on the hypothesis that both differences sport-related patterns of play and foot-ground interaction may lead to sport-specific muscle adaptations, this study compared the angle specific pronator and supinator strength capacity of handball and soccer players. Eighteen healthy male handball and 19 soccer players performed maximum isometric voluntary isometric contractions using a custom-made testing apparatus. Peak pronator (PPT) and supinator torques (PST), pronator and supinator strength curves (normalised to the peak torque across all joint angles) and PSR were measured in five anatomical joint angles across the active subtalar range of motion (ROM). All analysed parameters were dependent on the subtalar joint angle. The ANOVA revealed significant `joint angle' × `group' interactions on PPT, pronator strength curves and PSR. No group differences were found for active subtalar ROM. In previously uninjured handball and soccer athletes, there were intrinsic differences in angle-specific subtalar pronator muscle strength. The lower PSR, which was found in the most supinated angle, can be seen as a risk factor for sustaining an ankle sprain.

The Association of State Law to Physical Education Time Allocation in US Public Schools

PubMed Central

Oh, April; Chriqui, Jamie F.; Mâsse, Louise C.; Atienza, Audie A.; Nebeling, Linda; Agurs-Collins, Tanya; Moser, Richard P.; Dodd, Kevin W.

2012-01-01

Objectives. We examined whether public schools in states with specific and stringent physical education (PE) laws, as assessed by the Physical Education–Related State Policy Classification System (PERSPCS), available on the Classification of Laws Associated with School Students (C.L.A.S.S.) Web site, reported more weekly PE time in the most recent School Health Policies and Programs Survey (SHPPS). Methods. Schools (n = 410) were grouped by their state’s PERSPCS time requirement scores (none, nonspecific requirement, or specific requirement). Average weekly school-level PE was calculated using the SHPPS-reported PE minutes. Weighted analyses determined if PE minutes/week differed by PERSPCS group. Results. Schools in states with specific requirement laws averaged over 27 and 60 more PE minutes/week at the elementary and middle school levels, respectively, compared with schools within states with nonspecific laws and over 40 and 60 more PE minutes per week, respectively, compared with elementary and middle schools in states with no laws. High school results were nonsignificant. Conclusions. Public health guidelines recommend at least 60 minutes of daily physical activity for children, and PE may further this goal. Strong codified law with specific time requirements for PE may be an important tool contributing toward adequate PE time and daily physical activity recommendations. PMID:22594746

Mechanobiological simulations of peri-acetabular bone ingrowth: a comparative analysis of cell-phenotype specific and phenomenological algorithms.

PubMed

Mukherjee, Kaushik; Gupta, Sanjay

2017-03-01

Several mechanobiology algorithms have been employed to simulate bone ingrowth around porous coated implants. However, there is a scarcity of quantitative comparison between the efficacies of commonly used mechanoregulatory algorithms. The objectives of this study are: (1) to predict peri-acetabular bone ingrowth using cell-phenotype specific algorithm and to compare these predictions with those obtained using phenomenological algorithm and (2) to investigate the influences of cellular parameters on bone ingrowth. The variation in host bone material property and interfacial micromotion of the implanted pelvis were mapped onto the microscale model of implant-bone interface. An overall variation of 17-88 % in peri-acetabular bone ingrowth was observed. Despite differences in predicted tissue differentiation patterns during the initial period, both the algorithms predicted similar spatial distribution of neo-tissue layer, after attainment of equilibrium. Results indicated that phenomenological algorithm, being computationally faster than the cell-phenotype specific algorithm, might be used to predict peri-prosthetic bone ingrowth. The cell-phenotype specific algorithm, however, was found to be useful in numerically investigating the influence of alterations in cellular activities on bone ingrowth, owing to biologically related factors. Amongst the host of cellular activities, matrix production rate of bone tissue was found to have predominant influence on peri-acetabular bone ingrowth.

Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

NASA Astrophysics Data System (ADS)

Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

2013-08-01

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr32922d

The neural response in short-term visual recognition memory for perceptual conjunctions.

PubMed

Elliott, R; Dolan, R J

1998-01-01

Short-term visual memory has been widely studied in humans and animals using delayed matching paradigms. The present study used positron emission tomography (PET) to determine the neural substrates of delayed matching to sample for complex abstract patterns over a 5-s delay. More specifically, the study assessed any differential neural response associated with remembering individual perceptual properties (color only and shape only) compared to conjunction between these properties. Significant activations associated with short-term visual memory (all memory conditions compared to perceptuomotor control) were observed in extrastriate cortex, medial and lateral parietal cortex, anterior cingulate, inferior frontal gyrus, and the thalamus. Significant deactivations were observed throughout the temporal cortex. Although the requirement to remember color compared to shape was associated with subtly different patterns of blood flow, the requirement to remember perceptual conjunctions between these features was not associated with additional specific activations. These data suggest that visual memory over a delay of the order of 5 s is mainly dependent on posterior perceptual regions of the cortex, with the exact regions depending on the perceptual aspect of the stimuli to be remembered.

Markers of nonselective and specific NK cell activation.

PubMed

Fogel, Leslie A; Sun, Michel M; Geurs, Theresa L; Carayannopoulos, Leonidas N; French, Anthony R

2013-06-15

NK cell activation is controlled by the integration of signals from cytokine receptors and germline-encoded activation and inhibitory receptors. NK cells undergo two distinct phases of activation during murine CMV (MCMV) infection: a nonselective phase mediated by proinflammatory cytokines and a specific phase driven by signaling through Ly49H, an NK cell activation receptor that recognizes infected cells. We sought to delineate cell surface markers that could distinguish NK cells that had been activated nonselectively from those that had been specifically activated through NK cell receptors. We demonstrated that stem cell Ag 1 (Sca-1) is highly upregulated during viral infections (to an even greater extent than CD69) and serves as a novel marker of early, nonselective NK cell activation. Indeed, a greater proportion of Sca-1(+) NK cells produced IFN-γ compared with Sca-1(-) NK cells during MCMV infection. In contrast to the universal upregulation of Sca-1 (as well as KLRG1) on NK cells early during MCMV infection, differential expression of Sca-1, as well as CD27 and KLRG1, was observed on Ly49H(+) and Ly49H(-) NK cells late during MCMV infection. Persistently elevated levels of KLRG1 in the context of downregulation of Sca-1 and CD27 were observed on NK cells that expressed Ly49H. Furthermore, the differential expression patterns of these cell surface markers were dependent on Ly49H recognition of its ligand and did not occur solely as a result of cellular proliferation. These findings demonstrate that a combination of Sca-1, CD27, and KLRG1 can distinguish NK cells nonselectively activated by cytokines from those specifically stimulated through activation receptors.

Evolution of the construction and performances in accordance to the applications of non-thermal plasma reactors

NASA Astrophysics Data System (ADS)

Hnatiuc, B.; Brisset, J. L.; Astanei, D.; Ursache, M.; Mares, M.; Hnatiuc, E.; Felea, C.

2016-12-01

This paper aims to present the evolution of the construction and performances of non-thermal plasma reactors, identifying specific requirements for various known applications, setting out quality indicators that would allow on the one hand comparing devices that use different kinds of electrical discharges but also their rigorous classification by identification of criteria in order to choose the correct cold plasma reactors for a specific application. It briefly comments the post-discharge effect but also the current dilemma on non-thermal plasma direct treatments versus indirect treatments, using plasma activated water (PAW) or plasma activated medium (PAM), promising in cancer treatment.

Mapping lexical-semantic networks and determining hemispheric language dominance: Do task design, sex, age, and language performance make a difference?

PubMed

Chang, Yu-Hsuan A; Javadi, Sogol S; Bahrami, Naeim; Uttarwar, Vedang S; Reyes, Anny; McDonald, Carrie R

2018-04-01

Blocked and event-related fMRI designs are both commonly used to localize language networks and determine hemispheric dominance in research and clinical settings. We compared activation profiles on a semantic monitoring task using one of the two designs in a total of 43 healthy individual to determine whether task design or subject-specific factors (i.e., age, sex, or language performance) influence activation patterns. We found high concordance between the two designs within core language regions, including the inferior frontal, posterior temporal, and basal temporal region. However, differences emerged within inferior parietal cortex. Subject-specific factors did not influence activation patterns, nor did they interact with task design. These results suggest that despite high concordance within perisylvian regions that are robust to subject-specific factors, methodological differences between blocked and event-related designs may contribute to parietal activations. These findings provide important information for researchers incorporating fMRI results into meta-analytic studies, as well as for clinicians using fMRI to guide pre-surgical planning. Copyright © 2018 Elsevier Inc. All rights reserved.

Regulatory T-cell activity but not conventional HIV-specific T-cell responses are associated with protection from HIV-1 infection

PubMed Central

Pattacini, Laura; Baeten, Jared M.; Thomas, Katherine K.; Fluharty, Tayler R.; Murnane, Pamela M.; Donnell, Deborah; Bukusi, Elizabeth; Ronald, Allan; Mugo, Nelly; Lingappa, Jairam R.; Celum, Connie; McElrath, M. Juliana; Lund, Jennifer M.

2015-01-01

Objective Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated upon HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4+ T-cells, thereby diminishing the likelihood of infection. Methods To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). Results We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared to cases and was negatively associated with frequency of effector memory CD4+ T-cells. Conclusions Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection. PMID:26656786

In situ identification of nocardioform actinomycetes in activated sludge using fluorescent rRNA-targeted oligonucleotide probes.

PubMed

Schuppler, M; Wagner, M; Schön, G; Göbel, U B

1998-01-01

Hitherto, few environmental samples have been investigated by a 'full cycle rRNA analysis'. Here the results of in situ hybridization experiments with specific rRNA-targeted oligonucleotide probes developed on the basis of new sequences derived from a previously described comparative 16S rRNA analysis of nocardioform actinomycetes in activated sludge are reported. Application of the specific probes enabled identification and discrimination of the distinct populations of nocardioform actinomycetes in activated sludge. One of the specific probes (DLP) detected rod-shaped bacteria which were found in 13 of the 16 investigated sludge samples from various wastewater treatment plants, suggesting their importance in the wastewater treatment process. Another probe (GLP2) hybridized with typically branched filaments of nocardioforms mainly found in samples from enhanced biological phosphorus removal plants, suggesting that these bacteria are involved in sludge foaming. The combination of in situ hybridization with fluorescently labelled rRNA-targeted oligonucleotide probes and confocal laser scanning microscopy improved the detection of nocardioform actinomycetes, which often showed only weak signals inside the activated-sludge flocs.

Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease.

PubMed

Globig, Anna-Maria; Hennecke, Nadine; Martin, Bianca; Seidl, Maximilian; Ruf, Günther; Hasselblatt, Peter; Thimme, Robert; Bengsch, Bertram

2014-12-01

Skewed T helper (TH) cell responses and specific functions of TH1, TH2, TH17, and Treg cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) that led to the establishment of the pathogenic TH1/TH2 and TH17/Treg cell imbalance paradigms. However, the relevant TH cell population driving mucosal inflammation is still unknown. We performed a comprehensive TH cell profiling of circulating and intestinal lymphocytes isolated from patients with Crohn's disease (CD; n = 69) and ulcerative colitis (UC; n = 41) undergoing endoscopy or surgical resection and compared them with healthy controls (n = 45). Mucosal inflammation was assessed endoscopically and histologically. TH cells were analyzed by flow cytometric evaluation of cytokine production and differentiation marker expression. Specialized TH cell populations were enriched in the intestinal mucosa compared with peripheral blood. Specifically, we observed a concomitant upregulation of TH17 cells and Tregs in active inflammatory lesions in patients with both CD and UC compared with quiescent/mildly inflamed lesions and healthy tissue. Of note, interferon γ+ interleukin (IL)-17+coproducing CD4+ T cells with high expression of T-bet, CD26, and IL-22 resembling recently described pathogenic TH17 cells were specifically enriched in the inflamed mucosal tissue. Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells.

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major

PubMed Central

Catharina, Larissa; Lima, Carlyle Ribeiro; Franca, Alexander; Guimarães, Ana Carolina Ramos; Alves-Ferreira, Marcelo; Tuffery, Pierre; Derreumaux, Philippe; Carels, Nicolas

2017-01-01

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens. Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development. PMID:28638238

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major.

PubMed

Catharina, Larissa; Lima, Carlyle Ribeiro; Franca, Alexander; Guimarães, Ana Carolina Ramos; Alves-Ferreira, Marcelo; Tuffery, Pierre; Derreumaux, Philippe; Carels, Nicolas

2017-01-01

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens , only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens . Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development.

Nitrogen-doped hierarchical porous carbon microsphere through KOH activation for supercapacitors.

PubMed

Jiang, Jingui; Chen, Hao; Wang, Zhao; Bao, Luke; Qiang, Yiwei; Guan, Shiyou; Chen, Jianding

2015-08-15

A porous carbon microsphere with moderate specific surface area and superior specific capacitance for supercapacitors is fabricated from polyphosphazene microsphere as the single heteroatoms source by the carbonization and subsequent KOH activation under N2 atmosphere. With KOH activation, X-ray photoelectron spectroscopy analysis confirms that the phosphorus of polyphosphazene microsphere totally vanishes, and the doping content of nitrogen and its population of various functionalities on porous carbon microsphere surface are tuned. Compared with non-porous carbon microsphere, the texture property of the resultant porous carbon microsphere subjected to KOH activation has been remarkably developed with the specific surface area growing from 315 to 1341 m(2) g(-1)and the pore volume turning from 0.17 to 0.69 cm(3) g(-1). Prepared with the KOH/non-porous carbon microsphere weight ratio at 1.0, the porous carbon microsphere with moderate specific surface area of 568 m(2) g(-1), exhibits intriguing electrochemical behavior in 1 M H2SO4 aqueous electrolyte, with superior specific capacitance (278 F g(-1) at 0.1 A g(-1)), good rate capability (147 F g(-1) remained at 10 A g(-1)) and robust cycling durability (No capacitance loss after 5000 cycles). The promising electrochemical performance could be ascribed to the synergy of nitrogen heteroatom functionalities and the porous morphology. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular cloning, characterization and comparison of bile salt hydrolases from Lactobacillus johnsonii PF01.

PubMed

Chae, J P; Valeriano, V D; Kim, G-B; Kang, D-K

2013-01-01

To clone, characterize and compare the bile salt hydrolase (BSH) genes of Lactobacillus johnsonii PF01. The BSH genes were amplified by polymerase chain reaction (PCR) using specific oligonucleotide primers, and the products were inserted into the pET21b expression vector. Escherichia coli BLR (DE3) cells were transformed with pET21b vectors containing the BSH genes and induced using 0·1 mmol l(-1) isopropylthiolgalactopyranoside. The overexpressed BSH enzymes were purified using a nickel-nitrilotriacetic acid (Ni(2+) -NTA) agarose column and their activities characterized. BSH A hydrolysed tauro-conjugated bile salts optimally at pH 5·0 and 55°C, whereas BSH C hydrolysed glyco-conjugated bile salts optimally at pH 5·0 and 70°C. The enzymes had no preferential activities towards a specific cholyl moiety. BSH enzymes vary in their substrate specificities and characteristics to broaden its activity. Despite the lack of conservation in their putative substrate-binding sites, these remain functional through motif conservation. This is to our knowledge the first report of isolation of BSH enzymes from a single strain, showing hydrolase activity towards either glyco-conjugated or tauro-conjugated bile salts. Future structural homology studies and site-directed mutagenesis of sites associated with substrate specificity may elucidate specificities of BSH enzymes. © 2012 The Society for Applied Microbiology.

Perfectionism and sport-specific engagement in elite youth soccer players.

PubMed

Larkin, Paul; O'Connor, Donna; Williams, A Mark

2016-07-01

It is acknowledged that the time invested in sport-specific activities contributes to higher levels of performance. However, there is limited understanding of the potential impact of personality traits, such as perfectionism, on engagement in sport-specific activities. In the current study, we examine whether elite youth soccer players who demonstrate higher and lower levels of perfectionistic strivings tendencies can be differentiated based on their sport-specific engagement. The Sport Multidimensional Perfectionism Scale 2 and an adapted Player History Questionnaire were completed by 419 elite youth male soccer players competing at the Australian age-related national youth championships (under 13, n = 133; under 14, n = 166; under 15, n = 120). A quartile split approach was used to separate higher (n = 100) and lower (n = 107) perfectionistic strivings groups. Findings revealed the higher perfectionistic strivings group accumulated more time in sport-specific activities, including coach-led practice, individual practice, peer-led play and indirect involvement in soccer when compared to individuals with lower perfectionistic strivings tendencies. Descriptive analysis indicates this equates to approximately 159 h a year (i.e. 17 h coach-led practice, 22 h individual practice, 60 h of peer-led play and 60 h of indirect involvement) more than the lower perfectionistic strivings group. In summary, the results suggest players with varying levels of perfectionistic strivings may be differentiated based on their engagement in soccer-specific activity in a sample of elite youth players in Australia, and suggests that perfectionistic strivings may have an adaptive influence on sport-specific engagement.

NMR and Bioinformatics Discovery of Exosites That Tune Metalloelastase Specificity for Solubilized Elastin and Collagen Triple Helices*

PubMed Central

Palmier, Mark O.; Fulcher, Yan G.; Bhaskaran, Rajagopalan; Duong, Vinh Q.; Fields, Gregg B.; Van Doren, Steven R.

2010-01-01

The catalytic domain of metalloelastase (matrix metalloproteinase-12 or MMP-12) is unique among MMPs in exerting high proteolytic activity upon fibrils that resist hydrolysis, especially elastin from lungs afflicted with chronic obstructive pulmonary disease or arteries with aneurysms. How does the MMP-12 catalytic domain achieve this specificity? NMR interface mapping suggests that α-elastin species cover the primed subsites, a strip across the β-sheet from β-strand IV to the II–III loop, and a broad bowl from helix A to helix C. The many contacts may account for the comparatively high affinity, as well as embedding of MMP-12 in damaged elastin fibrils in vivo. We developed a strategy called BINDSIght, for bioinformatics and NMR discovery of specificity of interactions, to evaluate MMP-12 specificity without a structure of a complex. BINDSIght integration of the interface mapping with other ambiguous information from sequences guided choice mutations in binding regions nearer the active site. Single substitutions at each of ten locations impair specific activity toward solubilized elastin. Five of them impair release of peptides from intact elastin fibrils. Eight lesions also impair specific activity toward triple helices from collagen IV or V. Eight sites map to the “primed” side in the III–IV, V–B, and S1′ specificity loops. Two map to the “unprimed” side in the IV–V and B–C loops. The ten key residues circumscribe the catalytic cleft, form an exosite, and are distinctive features available for targeting by new diagnostics or therapeutics. PMID:20663866

Development and evaluation of the Andhra Pradesh Children and Parent Study Physical Activity Questionnaire (APCAPS-PAQ): a cross-sectional study.

PubMed

Matsuzaki, Mika; Sullivan, Ruth; Ekelund, Ulf; Krishna, K V Radha; Kulkarni, Bharati; Collier, Tim; Ben-Shlomo, Yoav; Kinra, Sanjay; Kuper, Hannah

2016-01-19

There is limited availability of context-specific physical activity questionnaires in low and middle income countries. The aim of this study was to develop and examine the validity of a new Indian physical activity questionnaire, the Andhra Pradesh Children and Parent Study Physical Activity Questionnaire (APCAPS-PAQ). The current study was conducted with the cohort from the Hyderabad DXA Study (n = 2321), recruited in 2009-2010. Criterion validity (n = 245) was examined by comparing the APCAPS-PAQ to a combined heart rate and motion sensor worn for 8 days. Construct validity (n = 2321) was assessed with linear regression, comparing APCAPS-PAQ against BMI, percent body fat, and pulse rate. The APCAPS-PAQ criterion validity was variable depending on the PA intensity groups (ρ = 0.26, 0.07, 0.39; к = 0.14, 0.04, 0.16 for sedentary, light, moderate/vigorous physical activity (MVPA) respectively). Sedentary and light intensity activities from the questionnaire were underestimated when compared to the criterion data while MVPA in APCAPS-PAQ was overestimated. Higher time spent in sedentary activity in APCAPS-PAQ was associated with higher BMI and percent body fat, suggesting construct validity. The APCAPS-PAQ validity is comparable to other physical activity questionnaires. This tool is able to assess sedentary behavior, moderate/vigorous activity and physical activity energy expenditure on a group level with reasonable validity. This new questionnaire may be used for ranking individuals according to their sedentary time and physical activity in southern India.

The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

PubMed

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2018-02-01

The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

A Comprehensive Study of Formic Acid Oxidation on Palladium Nanocrystals with Different Types of Facets and Twin Defects

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

Choi, Sang; Herron, Jeffrey A.; Scaranto, Jessica

2015-07-13

Palladium has been recognized as the best anodic, monometallic electrocatalyst for the formic acid oxidation (FAO) reaction in a direct formic acid fuel cell. Here we report a systematic study of FAO on a variety of Pd nanocrystals, including cubes, right bipyramids, octahedra, tetrahedra, decahedra, and icosahedra. These nanocrystals were synthesized with approximately the same size, but different types of facets and twin defects on their surfaces. Our measurements indicate that the Pd nanocrystals enclosed by {1 0 0} facets have higher specific activities than those enclosed by {1 1 1} facets, in agreement with prior observations for Pd single-crystalmore » substrates. If comparing nanocrystals predominantly enclosed by a specific type of facet, {1 0 0} or {1 1 1}, those with twin defects displayed greatly enhanced FAO activities compared to their single-crystal counterparts. To rationalize these experimental results, we performed periodic, self-consistent DFT calculations on model single-crystal substrates of Pd, representing the active sites present in the nanocrystals used in the experiments. The calculation results suggest that the enhancement of FAO activity on defect regions, represented by Pd(2 1 1) sites, compared to the activity of both Pd(1 0 0) and Pd(1 1 1) surfaces, could be attributed to an increased flux through the HCOO-mediated pathway rather than the COOH-mediated pathway on Pd(2 1 1). Since COOH has been identified as a precursor to CO, a site-poisoning species, a lower coverage of CO at the defect regions will lead to a higher activity for the corresponding nanocrystal catalysts, containing those defect regions.« less

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

Situated Meaning-Making of the Human Body: A Study of Elementary School Children's Reasons in Two Different Activities

ERIC Educational Resources Information Center

Lundin, Mattias; Jakobson, Britt

2014-01-01

In this text we compare children's expressions in drawings to their statements during interviews, for the purpose of understanding how different situations afford children to make meaning. In specific we study how two different activities interact and afford children to make meaning differently about the human body. The analytic attention is…

A mixed-method study on the generic and ostomy-specific quality of life of cancer and non-cancer ostomy patients.

PubMed

Jansen, Femke; van Uden-Kraan, Cornelia F; Braakman, J Annemieke; van Keizerswaard, Paulina M; Witte, Birgit I; Verdonck-de Leeuw, Irma M

2015-06-01

The aim of this study is to compare the generic and ostomy-specific quality of life (QoL) between cancer and non-cancer ostomy patients using a mixed-method design. All patients with an ostomy participating in the Stomapanel of the Dutch Ostomy Association were asked to complete a generic (RAND-36) and ostomy-specific (Stoma-QoL) QoL questionnaire. In addition, open-ended questions on symptoms, restrictions or adaptations influencing daily life were included. The generic and ostomy-specific QoL between cancer and non-cancer ostomy patients were compared using linear regression analyses. Qualitative responses were analysed using content analysis. In total, 668 patients were included: 379 cancer patients (80 % colorectal, 17 % bladder and 3 % other) and 289 non-cancer patients (38 % colitis ulcerosa, 22 % Crohn's disease and 40 % other) with a colostomy (55 %), ileostomy (31 %) and/or urostomy (16 %). Adjusted for gender, age, type of ostomy and time elapsed since ostomy surgery, cancer ostomy patients scored higher (better) on Stoma-QoL (β = 2.1) and all RAND-36 domains (9.1 < β ≤ 19.5) except on mental health compared to non-cancer ostomy patients. Of the 33 themes coded for in the content analysis, fatigue or sleeplessness, leakages, pain, bladder or bowel complaints, physical functioning or activity, travelling or being away from home, other daily activities (including work), clothing and diet were among the 10 most frequently reported themes, although ranking differed between both patient groups. Besides, cancer ostomy patients frequently reported on the impact on (engaging in a) relationship or sexual intimacy and non-cancer ostomy patients frequently reported to be relieved of symptoms and restrictions in daily life. Cancer patients reported better generic and ostomy-specific QoL than non-cancer ostomy patients. In both cancer and non-cancer ostomy patients, fatigue or sleeplessness, leakages, pain, bladder or bowel complaints, physical functioning or activity, travelling or being away from home, other daily activities (including work), clothing and diet were among the 10 most common reported themes influencing daily life. However, the ranking of these 10 most common themes was different in both patient groups.

Bacterial activity in sea ice and open water of the Weddell Sea, Antarctica: A microautoradiographic study.

PubMed

Grossmann, S

1994-07-01

Metabolic activity of bacteria was investigated in open water, newly forming sea ice, and successive stages of pack ice in the Weddell Sea. Microautoradiography, using [(3)H]leucine as substrate, was compared with incorporation rates of [(3)H]leucine into proteins. Relation of [(3)H]leucine incorporation to the biomass of active bacteria provides information about changes of specific metabolic activity of cells. During a phytoplankton bloom in an ice-free, stratified water column, total numbers of bacteria in the euphotic zone averaged 2.3 × 10(5) ml(-1), but only about 13% showed activity via leucine uptake. Growth rate of the active bacteria was estimated as 0.3-0.4 days(-1). Total cell concentration of bacteria in 400 m depth was 6.6 × 10(4) ml(-1). Nearly 50% of these cells were active, although biomass production and specific growth rate were only about one-tenth that of the surface populations. When sea ice was forming in high concentrations of phytoplankton, bacterial biomass in the newly formed ice was 49.1 ng C ml(-1), exceeding that in open water by about one order of magnitude. Attachment of large bacteria to algal cells seems to cause their enrichment in the new ice, since specific bacterial activity was reduced during ice formation, and enrichment of bacteria was not observed when ice formed at low algal concentration. During growth of pack ice, biomass of bacteria increased within the brine channel system. Specific activity was still reduced at these later stages of ice development, and percentages of active cells were as low as 3-5%. In old, thick pack ice, bacterial activity was high and about 30% of cells were active. However, biomass-specific activity of bacteria remained significantly lower than that in open water. It is concluded that bacterial assemblages different to those of open water developed within the ice and were dominated by bacteria with lower average metabolic activity than those of ice-free water.

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

Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

PubMed

Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

2016-05-01

CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

A specific, transmembrane interface regulates fibroblast activation protein (FAP) homodimerization, trafficking and exopeptidase activity.

PubMed

Wonganu, Benjamaporn; Berger, Bryan W

2016-08-01

Fibroblast activation protein (FAP) is a cell-surface serine protease which promotes invasiveness of certain epithelial cancers and is therefore a potential target for cancer drug development and delivery. Unlike dipeptidyl peptidase IV (DPPIV), FAP exhibits prolyl endopeptidase activity and is active as a homodimer with specificity for type I collagen. The mechanism that regulates FAP homodimerization and its relation to prolyl endopeptidase activity is not completely understood. Here, we investigate key residues in the FAP TM domain that may be significant for FAP homodimerization. Mutations to predicted TM interfacial residues (G10L, S14L, and A18L) comprising a small-X3-small motif reduced FAP TM-CYTO dimerization relative to wild type as measured using the AraTM assay, whereas predicted off-interface residues showed no significant change from wild type. The results implied that the predicted small-X3-small dimer interface affect stabilization of FAP TM-CYTO homodimerization. Compared with FAPwild-type, the interfacial TM residue G10L significantly decreased FAP endopeptidase activity more than 25%, and also reduced cell-surface versus intracellular expression relative to other interfacial residues S14L and A18L. Thus, our results suggest FAP dimerization is important for both trafficking and protease activity, and is dependent on a specific TM interface. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of lithium-thionyl chloride batteries for Centaur

NASA Technical Reports Server (NTRS)

Halpert, Gerald; Frank, Harvey; Lutwack, Ralph

1987-01-01

Lithium thionyl chloride (LiSOCl2) primary cells and batteries have received considerable attention over the last several years because of their high theoretical specific energy and energy density. The objective was to develop a 300 wh/kg cell capable of safe operation at C/2 rate and active storage life for 5 to 10 years. This technology would replace other primary cell technologies in NASA applications mainly the silver zinc (AgZn) batteries presently in use. The LiSOCl2 system exceeds the capabilities of the AgZn in terms of specific energy of 300 wh/kg (compared with 100 wh/kg for AgZn), active storage life of 10 to 20 times the 3 to 6 months active storage and has a significantly lower projected cost.

Development of lithium-thionyl chloride batteries for Centaur

NASA Technical Reports Server (NTRS)

Halpert, Gerald; Frank, Harvey; Lutwack, Ralph

1988-01-01

Lithium thionyl chloride (LiSOCl2) primary cells and batteries have received considerable attention over the last several years because of their high theoretical specific energy and energy density. The objective was to develop a 300 wh/kg cell capable of safe operation at C/2 rate and active storage life for 5 to 10 years. This technology would replace other primary cell technologies in NASA applications mainly the silver zinc (AgZn) batteries presently in use. The LiSOCl2 system exceeds the capabilities of the AgZn in terms of specific energy of 300 wh/kg (compared with 100 wh/kg for AgZn), active storage life of 10 to 20 times the 3 to 6 months active storage and has a significantly lower projected cost.

Pericyclic reactions catalyzed by chorismate-utilizing enzymes

PubMed Central

Lamb, Audrey L.

2011-01-01

One of the fundamental questions of enzymology is how catalytic power is derived. This review focuses on recent developments in the structure-function relationships of chorismate-utilizing enzymes involved in siderophore biosynthesis to provide insight into the biocatalysis of pericyclic reactions. Specifically, salicylate synthesis by the two-enzyme pathway in Pseudomonas aeruginosa is examined. The isochorismate-pyruvate lyase is discussed in the context of its homologues, the chorismate mutases, and the isochorismate synthase is compared to its homologues in the MST-family (menaquinone, siderophore or tryptophan biosynthesis) of enzymes. The tentative conclusion is that the activities observed cannot be reconciled by inspection of the active site participants alone. Instead, individual activities must arise from unique dynamic properties of each enzyme that are tuned to promote specific chemistries. PMID:21823653

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.

CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells.

PubMed

Selb, Regina; Eckl-Dorna, Julia; Neunkirchner, Alina; Schmetterer, Klaus; Marth, Katharina; Gamper, Jutta; Jahn-Schmid, Beatrice; Pickl, Winfried F; Valenta, Rudolf; Niederberger, Verena

2017-01-01

Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. In allergic patients the vast majority of CD23 molecules were expressed on naive IgD + B cells. The density of CD23 molecules on B cells but not the number of CD23 + cells correlated with total IgE levels (R S  = 0.53, P = .03) and allergen-induced skin reactions (R S  = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

WAVE2 forms a complex with PKA and is involved in PKA enhancement of membrane protrusions.

PubMed

Yamashita, Hiroshi; Ueda, Kazumitsu; Kioka, Noriyuki

2011-02-04

PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation.

The maximum specific hydrogen-producing activity of anaerobic mixed cultures: definition and determination

PubMed Central

Mu, Yang; Yang, Hou-Yun; Wang, Ya-Zhou; He, Chuan-Shu; Zhao, Quan-Bao; Wang, Yi; Yu, Han-Qing

2014-01-01

Fermentative hydrogen production from wastes has many advantages compared to various chemical methods. Methodology for characterizing the hydrogen-producing activity of anaerobic mixed cultures is essential for monitoring reactor operation in fermentative hydrogen production, however there is lack of such kind of standardized methodologies. In the present study, a new index, i.e., the maximum specific hydrogen-producing activity (SHAm) of anaerobic mixed cultures, was proposed, and consequently a reliable and simple method, named SHAm test, was developed to determine it. Furthermore, the influences of various parameters on the SHAm value determination of anaerobic mixed cultures were evaluated. Additionally, this SHAm assay was tested for different types of substrates and bacterial inocula. Our results demonstrate that this novel SHAm assay was a rapid, accurate and simple methodology for determining the hydrogen-producing activity of anaerobic mixed cultures. Thus, application of this approach is beneficial to establishing a stable anaerobic hydrogen-producing system. PMID:24912488

The active principle region of Buyang Huanwu decoction induced differentiation of bone marrow-derived mesenchymal stem cells into neural-like cells

PubMed Central

Zheng, Jinghui; Wan, Yi; Chi, Jianhuai; Shen, Dekai; Wu, Tingting; Li, Weimin; Du, Pengcheng

2012-01-01

The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction (active principle region of decoction for invigorating yang for recuperation). After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula. PMID:25806066

Anchoring of ulex europaeus agglutinin to chitosan nanoparticles-in-microparticles and their in vitro binding activity to bovine submaxillary gland mucin.

PubMed

Li, Feng-Qian; Fei, Yi-Bo; Chen, Xu; Qin, Xian-Ju; Liu, Ji-Yong; Zhu, Quan-Gang; Hu, Jin-Hong

2009-10-01

Focused on the natural biodegradable material of chitosan (CS), this investigation concerned its spray-dried nanoparticles-in-microparticles (NiMPs) modified with ulex europaeus agglutinin (UEA). Chitosan nanoparticles were obtained by ionotropic gelation process with pentasodium tripolyphosphate as gelatinizer. Then UEA lectin was bound onto the CS nanoparticles activated by glutaraldehyde. The conjugated spherical UEA-CS-NiMPs, prepared by spray drying method, exhibited 12-85% coupling efficiency of UEA depending upon the amount of activator glutaraldehyde. And the UEA-grafted particles showed additional higher binding tendency with bovine submaxillary gland mucin as compared to the plain chitosan microparticles. Furthermore, the activity and intrinsic fucose-specificity of UEA were still maintained after the covalent modification. It is thus evident that the UEA anchored CS-NiMPs might be used as a potential drug delivery system targeted to the specific regions of gastrointestinal tract.

The maximum specific hydrogen-producing activity of anaerobic mixed cultures: definition and determination

NASA Astrophysics Data System (ADS)

Mu, Yang; Yang, Hou-Yun; Wang, Ya-Zhou; He, Chuan-Shu; Zhao, Quan-Bao; Wang, Yi; Yu, Han-Qing

2014-06-01

Fermentative hydrogen production from wastes has many advantages compared to various chemical methods. Methodology for characterizing the hydrogen-producing activity of anaerobic mixed cultures is essential for monitoring reactor operation in fermentative hydrogen production, however there is lack of such kind of standardized methodologies. In the present study, a new index, i.e., the maximum specific hydrogen-producing activity (SHAm) of anaerobic mixed cultures, was proposed, and consequently a reliable and simple method, named SHAm test, was developed to determine it. Furthermore, the influences of various parameters on the SHAm value determination of anaerobic mixed cultures were evaluated. Additionally, this SHAm assay was tested for different types of substrates and bacterial inocula. Our results demonstrate that this novel SHAm assay was a rapid, accurate and simple methodology for determining the hydrogen-producing activity of anaerobic mixed cultures. Thus, application of this approach is beneficial to establishing a stable anaerobic hydrogen-producing system.

Domain-General and Domain-Specific Patterns of Activity Supporting Metacognition in Human Prefrontal Cortex

PubMed Central

2018-01-01

Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. SIGNIFICANCE STATEMENT We used human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks or if self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations coexist with generic confidence signals. Our findings reconcile previously conflicting results on the domain specificity/generality of metacognition and lay the groundwork for a mechanistic understanding of metacognitive judgments. PMID:29519851

Measurements of weak interactions between truncated substrates and a hammerhead ribozyme by competitive kinetic analyses: implications for the design of new and efficient ribozymes with high sequence specificity

PubMed Central

Kasai, Yasuhiro; Shizuku, Hideki; Takagi, Yasuomi; Warashina, Masaki; Taira, Kazunari

2002-01-01

Exploitation of ribozymes in a practical setting requires high catalytic activity and strong specificity. The hammerhead ribozyme R32 has considerable potential in this regard since it has very high catalytic activity. In this study, we have examined how R32 recognizes and cleaves a specific substrate, focusing on the mechanism behind the specificity. Comparing rates of cleavage of a substrate in a mixture that included the correct substrate and various substrates with point mutations, we found that R32 cleaved the correct substrate specifically and at a high rate. To clarify the source of this strong specificity, we quantified the weak interactions between R32 and various truncated substrates, using truncated substrates as competitive inhibitors since they were not readily cleaved during kinetic measurements of cleavage of the correct substrate, S11. We found that the strong specificity of the cleavage reaction was due to a closed form of R32 with a hairpin structure. The self-complementary structure within R32 enabled the ribozyme to discriminate between the correct substrate and a mismatched substrate. Since this hairpin motif did not increase the Km (it did not inhibit the binding interaction) or decrease the kcat (it did not decrease the cleavage rate), this kind of hairpin structure might be useful for the design of new ribozymes with strong specificity and high activity. PMID:12034825

Muscle-specific deletion of exons 2 and 3 of the IL15RA gene in mice: effects on contractile properties of fast and slow muscles.

PubMed

O'Connell, Grant; Guo, Ge; Stricker, Janelle; Quinn, LeBris S; Ma, Averil; Pistilli, Emidio E

2015-02-15

Interleukin-15 (IL-15) is a putative myokine hypothesized to induce an oxidative skeletal muscle phenotype. The specific IL-15 receptor alpha subunit (IL-15Rα) has also been implicated in specifying this contractile phenotype. The purposes of this study were to determine the muscle-specific effects of IL-15Rα functional deficiency on skeletal muscle isometric contractile properties, fatigue characteristics, spontaneous cage activity, and circulating IL-15 levels in male and female mice. Muscle creatine kinase (MCK)-driven IL-15Rα knockout mice (mIl15ra(fl/fl)/Cre(+)) were generated using the Cre-loxP system. We tested the hypothesis that IL-15Rα functional deficiency in skeletal muscle would increase resistance to contraction-induced fatigue, cage activity, and circulating IL-15 levels. There was a significant effect of genotype on the fatigue curves obtained in extensor digitorum longus (EDL) muscles from female mIl15ra(fl/fl)/Cre(+) mice, such that force output was greater during the repeated contraction protocol compared with mIl15ra(fl/fl)/Cre(-) control mice. Muscles from female mIl15ra(fl/fl)/Cre(+) mice also had a twofold greater amount of the mitochondrial genome-specific COXII gene compared with muscles from mIl15ra(fl/fl)/Cre(-) control mice, indicating a greater mitochondrial density in these skeletal muscles. There was a significant effect of genotype on the twitch:tetanus ratio in EDL and soleus muscles from mIl15ra(fl/fl)/Cre(+) mice, such that the ratio was lower in these muscles compared with mIl15ra(fl/fl)/Cre(-) control mice, indicating a pro-oxidative shift in muscle phenotype. However, spontaneous cage activity was not different and IL-15 protein levels were lower in male and female mIl15ra(fl/fl)/Cre(+) mice compared with control. Collectively, these data support a direct effect of muscle IL-15Rα deficiency in altering contractile properties and fatigue characteristics in skeletal muscles.

Structural model of the open–closed–inactivated cycle of prokaryotic voltage-gated sodium channels

PubMed Central

Bagnéris, Claire; Naylor, Claire E.; McCusker, Emily C.

2015-01-01

In excitable cells, the initiation of the action potential results from the opening of voltage-gated sodium channels. These channels undergo a series of conformational changes between open, closed, and inactivated states. Many models have been proposed for the structural transitions that result in these different functional states. Here, we compare the crystal structures of prokaryotic sodium channels captured in the different conformational forms and use them as the basis for examining molecular models for the activation, slow inactivation, and recovery processes. We compare structural similarities and differences in the pore domains, specifically in the transmembrane helices, the constrictions within the pore cavity, the activation gate at the cytoplasmic end of the last transmembrane helix, the C-terminal domain, and the selectivity filter. We discuss the observed differences in the context of previous models for opening, closing, and inactivation, and present a new structure-based model for the functional transitions. Our proposed prokaryotic channel activation mechanism is then compared with the activation transition in eukaryotic sodium channels. PMID:25512599

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.

Immobilization of cellulase on a silica gel substrate modified using a 3-APTES self-assembled monolayer

DOE PAGES

Zhang, Dezhi; Hegab, Hisham E.; Lvov, Yuri; ...

2016-01-20

Cellulase was immobilized onto silica gel surfaces pretreated with (3-aminopropyl) triethoxy-silane (3-APTES), and glutaraldehyde (GA) was used as a cross-linker. A carboxymethyl cellulose sodium salt (CMC) solution was used for activity experiments. Protein assay was performed to determine the mass immobilized and compare with free enzyme. Cellulase was successfully demonstrated to be immobilized on the modified silica gel surface, and no detectable amount of enzyme was stripped off during the hydrolysis of the CMC solution. The specific activity of the immobilized cellulase is 7 ± 2 % compared to the similar amount of free cellulase. Significant activity over multiple reusesmore » was observed. The seventh batch achieved 82 % activity of the initial batch, and the fifteenth batch retained 31 %. Lastly, it was observed that the immobilized cellulase retained 48 % of its initial activity after 4 days, and 22 % even after 14 days.« less

The effect of the lectin from Cherax quadricarinatus on its granular hemocytes.

PubMed

Sánchez-Salgado, José Luis; Pereyra, Mohamed Alí; Agundis, Concepción; Vivanco-Rojas, Oscar; Rosales, Carlos; Pascual, Cristina; Alpuche-Osorno, Juan José; Zenteno, Edgar

2018-06-01

In crustaceans, lectins and hemocytes of the innate immune system provide the first line of defense. Although evidence points to the potential role of lectins in regulating hemocyte activity, the processes underlying the lectin activation have not been evaluated. In the present study, the receptor for CqL, a humoral lectin from Cherax quadricarinatus specific for galactose/sialic acid, was identified in a granular subset of hemocytes. The CqL receptor (CqLR) is a 490-kDa glycoprotein, composed of four identical 120-kDa subunits. As shown by immunohistochemistry, CqL at 7.5 μg/mL as optimal dose, after 2 min, induced, specifically on granular hemocytes, increased phosphorylation of serine (152%), threonine (192%), and tyrosine (242%) as compared with non-treated hemocytes; moreover, CqL induced increased generation of reactive oxygen species (ROS). Specific kinase inhibitors showed inhibition (P < 0.001) of ROS production induced by CqL. These results strongly suggest that CqL actively participated in the generation of ROS through kinases induced by a CqLR in a subset of granular hemocytes of the crayfish C. quadricarinatus. The results provide strong evidence that CqL activates, through specific granular hemocytes, receptors that modulate cellular functions in C. quadricarinatus. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measurement and Analysis of Specific Activities of Natural Radionuclides (40K, 226Ra and 232Th) in Beach Sand Samples from Talo Kapo Beach of Yaring District in Pattani Province using Gamma Ray Spectrometry

NASA Astrophysics Data System (ADS)

Daoh, M.; Masae, R. N.; Po-oh, S.; Boonkrongcheep; Kessaratikoon, P.

2017-09-01

The Specific Activities of 40K, 226Ra and 232Th were studied and determinate for 30 beach sand samples collected from Talo Kapo beach of Yaring district in Pattani province. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system. The IAEA-SOIL-6 reference materials obtained from the International Atomic Energy Agency were also used to analyze and compute the 40K, 226Ra and 232Th specific activity in all 30 beach sand samples. The measuring time of each sample is 10,000 seconds. It was found that specific activity range from 1805.37 - 3323.05, 40.96 - 2137.36 38.63 - 4329.28 Bq/kg for with mean values of 2242.79 ± 117.40, 250.18 ± 8.21 and 458.42 ± 7.68 Bq/kg for 40K, 226Ra and 232Th, respectively. Moreover, the results were also compared with research data in the south of Thailand, the Office of Atoms for Peace (OAP) annual report data and the recommended values which were proposed by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR,)

Segregated and integrated coding of reward and punishment in the cingulate cortex.

PubMed

Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro

2009-06-01

Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.

Comparative Study on Different Expression Hosts for Alkaline Phytase Engineered in Escherichia coli.

PubMed

Chen, Weiwei; Yu, Hongwei; Ye, Lidan

2016-07-01

The application of alkaline phytase as a feed additive is restricted by the poor specific activity. Escherichia coli is a frequently used host for directed evolution of proteins including alkaline phytase towards improved activity. However, it is not suitable for production of food-grade products due to potential pathogenicity. To combine the advantages of different expression systems, mutants of the alkaline phytase originated from Bacillus subtilis 168 (phy168) were first generated via directed evolution in E. coli and then transformed to food-grade hosts B. subtilis and Pichia pastoris for secretory expression. In order to investigate the suitability of different expression systems, the phy168 mutants expressed in different hosts were characterized and compared in terms of specific activity, pH profile, pH stability, temperature profile, and thermostability. The specific activity of B. subtilis-expressed D24G/K70R/K111E/N121S mutant at pH 7.0 and 60 °C was 30.4 U/mg, obviously higher than those in P. pastoris (22.7 U/mg) and E. coli (19.7 U/mg). Moreover, after 10 min incubation at 80 °C, the B. subtilis-expressed D24G/K70R/K111E/N121S retained about 70 % of the activity at pH 7.0 and 37 °C, whereas the values were only about 25 and 50 % when expressed in P. pastoris and E. coli, respectively. These results suggested B. subtilis as an appropriate host for expression of phy168 mutants and that the strategy of creating mutants in one host and expressing them in another might be a new solution to industrial production of proteins with desired properties.

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

PubMed

Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

2018-06-01

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

Alteration of O-GlcNAcylation affects serine phosphorylation and regulates gene expression and activity of pyruvate kinase M2 in colorectal cancer cells.

PubMed

Chaiyawat, Parunya; Chokchaichamnankit, Daranee; Lirdprapamongkol, Kriengsak; Srisomsap, Chantragan; Svasti, Jisnuson; Champattanachai, Voraratt

2015-10-01

O-GlcNAcylation is a dynamic post-translational modification that has extensive crosstalk with phosphorylation either at the same or adjacent sites of various proteins. We have previously reported that O-GlcNAcylation level was increased in primary breast and colorectal cancer, but the interplay of the two modifications remains unclear. Therefore, we explored crosstalk of the modifications by RNA interference against O-GlcNAc transferase (OGT) in colorectal cancer cells. Two-dimensional immunoblotting and mass spectrometric analysis showed that the levels of O-GlcNAc and serine phosphorylation of many proteins including serine hydroxymethyltransferase, cytokeratin-8, pyruvate kinase M2 (PKM2), heterogeneous nuclear ribonucleoprotein L, and lamin-B1, were reduced in siOGT cells compared to siScramble cells. In HT29 cells, immunoprecipitated PKM2 revealed decreased O-GlcNAc and serine phosphorylation levels after siOGT knockdown, but increased levels after treatment with Thiamet-G, an inhibitor of O-GlcNAcase (OGA). In addition, when global O-GlcNAcylation was enhanced by treating cells with Thiamet-G, PKM2 expression level was upregulated, but PKM2-specific activity was decreased. On the other hand, in OGT knockdown cells, PKM2 expression level was downregulated, but PKM2-specific activity was increased. Moreover, the metastatic colorectal cancer cells, SW620, had more O-GlcNAc-PKM2 and showed lower PKM2-specific activity compared to the non-metastatic colorectal cancer SW480 cells. These results suggested roles of O-GlcNAcylation in modulating serine phosphorylation, as well as in regulating PKM2 activity and expression. Interfering levels of O-GlcNAcylation of PKM2 may be a novel target in controlling cancer metabolism and tumorigenesis of colorectal cancer.

Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children.

PubMed

Varga, E-M; Francis, J N; Zach, M S; Klunker, S; Aberer, W; Durham, S R

2009-09-01

Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment=104+/-23%; 2 years=46+/-15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6+/-2.3 AU; 2 years=26.7+/-3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44+/-7 AU) in sera obtained after 2 years of VIT (25+/-5 AU; P<0.01) and 2 years following the withdrawal of VIT (10+/-3 AU; P<0.05). In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT.

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

PubMed Central

Brust, Belinda; Lecoufle, Mélanie; Tuaillon, Edouard; Dedieu, Luc; Canaan, Stéphane; Valverde, Viviane; Kremer, Laurent

2011-01-01

Background New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. Methods Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. Results A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. Conclusion These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB. PMID:21966416

Comparing Paper and Tablet Modes of Retrospective Activity Space Data Collection.

PubMed

Yabiku, Scott T; Glick, Jennifer E; Wentz, Elizabeth A; Ghimire, Dirgha; Zhao, Qunshan

2017-01-01

Individual actions are both constrained and facilitated by the social context in which individuals are embedded. But research to test specific hypotheses about the role of space on human behaviors and well-being is limited by the difficulty of collecting accurate and personally relevant social context data. We report on a project in Chitwan, Nepal, that directly addresses challenges to collect accurate activity space data. We test if a computer assisted interviewing (CAI) tablet-based approach to collecting activity space data was more accurate than a paper map-based approach; we also examine which subgroups of respondents provided more accurate data with the tablet mode compared to paper. Results show that the tablet approach yielded more accurate data when comparing respondent-indicated locations to the known locations as verified by on-the-ground staff. In addition, the accuracy of the data provided by older and less healthy respondents benefited more from the tablet mode.

Comparing Paper and Tablet Modes of Retrospective Activity Space Data Collection*

PubMed Central

Yabiku, Scott T.; Glick, Jennifer E.; Wentz, Elizabeth A.; Ghimire, Dirgha; Zhao, Qunshan

2018-01-01

Individual actions are both constrained and facilitated by the social context in which individuals are embedded. But research to test specific hypotheses about the role of space on human behaviors and well-being is limited by the difficulty of collecting accurate and personally relevant social context data. We report on a project in Chitwan, Nepal, that directly addresses challenges to collect accurate activity space data. We test if a computer assisted interviewing (CAI) tablet-based approach to collecting activity space data was more accurate than a paper map-based approach; we also examine which subgroups of respondents provided more accurate data with the tablet mode compared to paper. Results show that the tablet approach yielded more accurate data when comparing respondent-indicated locations to the known locations as verified by on-the-ground staff. In addition, the accuracy of the data provided by older and less healthy respondents benefited more from the tablet mode. PMID:29623133

[A comparative study on hydrolase activities in Acanthamoeba culbertsoni and A. royreba

PubMed

Kim, Yong Kyu; Kim, Tae Ue; Joung, In Sil; Im, Kyung Il

1988-06-01

Specific or non-specific cytolytic processes of free-living amoebae causing meningoencephalitis have been emphasized and the cytolytic ability related to hydrolases in Entamoeba sp. and Naegleria sp. has also been reported since the latter half of 1970's. However, no information on hydrolase activities in Acanthamoeba sp. is available. Hydrolases in Acanthamoeba culbertsoni, a pathogenic species of free-living amoebae, were assayed and compared with those in a non-pathogenic species, A. royreba. Pathogenicity of these two species was confirmed through experimental infection to BALB/c mice. Hydrolase activities and cytotoxic effects between pathogenic and non-pathogenic species were compared in the trophozoites cultured in CGV media and in CHO cell line, respectively. The results are summarized as follows: The mice infected with A. culbertsoni were all dead 15 days after nasal inoculation, and the mean survival time was 8.5 days. Also the mice infected with this pathogenic species mani fested typical meningoencephalitis, whereas the mice infected with A. royreba did not. Hydrolases detected both in the cell extracts and culture media were acid phosphatase, beta-N-acetyl galactosaminidase, beta-N-acetyl glucosaminidase, alpha-mannosidase, neutral proteinase and acid proteinase, all of which were detected with remarkably higher rate in A.culbertsoni than in A. royreba. A. culbertsoni revealed strong cytotoxicity for the target CHO cells, whereas A. royreba did not show any specific cytotoxicity. About 80% of the target cells mixed with A. culbertsoni were dead 48 hours after cultivation, and more than 95% of the target cells were dead 72 hours after cultivation. Hydrolase activities in A. culbertsoni cultured with the target cell line were assayed according to the culture time. The activities of acid phosphatase, beta-N-acetyl glucosaminidase, beta-N-acetyl glucosaminidase, alpha-mannosidase and acid proteinase in this pathogenic amoeba were detected higher in amoeba extracts than in culture media up to 120 hours after cultivation, but after 120 hours of cultivation those activities were detected higher in culture media than in the amoeba lysates. Neutral proteinase activity in A. culbertsoni increased more in EBSS medium than in the lysate specimens although the activity in the extracts was generally steady according to the cultivation time. Summarizing the above results, it is concluded that there were differences in hydrolase activities between pathogenic A. culbertsoni and non-pathogenic A. royreba, and that some hydrolase activities were detected remarkably higher in A. culbertsoni which revealed strong cytotoxicity to the target CHO cell line.

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.

Prefrontal Neural Activity When Feedback Is Not Relevant to Adjust Performance

PubMed Central

Özyurt, Jale; Rietze, Mareike; Thiel, Christiane M.

2012-01-01

It has been shown that the rostral cingulate zone (RCZ) in humans uses both positive and negative feedback to evaluate performance and to flexibly adjust behaviour. Less is known on how the feedback types are processed by the RCZ and other prefrontal brain areas, when feedback can only be used to evaluate performance, but cannot be used to adjust behaviour. The present fMRI study aimed at investigating feedback that can only be used to evaluate performance in a word-learning paradigm. One group of volunteers (N = 17) received informative, performance-dependent positive or negative feedback after each trial. Since new words had to be learnt in each trial, the feedback could not be used for task-specific adaptations. The other group (N = 17) always received non-informative feedback, providing neither information about performance nor about possible task-specific adaptations. Effects of the informational value of feedback were assessed between-subjects, comparing trials with positive and negative informative feedback to non-informative feedback. Effects of feedback valence were assessed by comparing neural activity to positive and negative feedback within the informative-feedback group. Our results show that several prefrontal regions, including the pre-SMA, the inferior frontal cortex and the insula were sensitive to both, the informational value and the valence aspect of the feedback with stronger activations to informative as compared to non-informative feedback and to informative negative compared to informative positive feedback. The only exception was RCZ which was sensitive to the informational value of the feedback, but not to feedback valence. The findings indicate that outcome information per se is sufficient to activate prefrontal brain regions, with the RCZ being the only prefrontal brain region which is equally sensitive to positive and negative feedback. PMID:22615774

Do sporting activities convey benefits to bone mass throughout the skeleton?

PubMed

Nevill, Alan; Holder, Roger; Stewart, Arthur

2004-07-01

It is well known that sport and exercise play an important role in stimulating site-specific bone mineral density (BMD). However, what is less well understood is how these benefits dissipate throughout the body. Hence, the aim of the present study was to compare the BMD (recorded at nine sites throughout the skeleton) of 106 male athletes (from nine sports) with that of 15 male non-exercising age-matched controls. Given that BMD is known to increase with body mass and peak with age, multivariate and univariate analyses of covariance were performed to compare the BMD of the nine sports groups with controls (at all sites) using body mass and age as covariates. Our results confirmed a greater adjusted BMD in the arms of the upper-body athletes, the right arm of racket players and the legs of runners (compared with controls), supporting the site-specific nature (i.e. specific to the externally loaded site) of the bone remodelling response (all P <0.01). However, evidence that bone mass acquisition is not just site-specific comes from the results of the rugby players, strength athletes, triathletes and racket players. The rugby players' adjusted BMD was the greatest of all sports groups and greater than controls at all nine sites (all P <0.01), with differences ranging from 8% greater in the left arm to 21% in the lumbar spine. Similarly, the strength athletes' adjusted BMD was superior to that of controls at all sites (P <0.05) except the legs. The adjusted BMD of the triathletes was significantly greater than that of the controls in both the arms and the legs as well as the thoracic and lumbar spine. The racket players not only had significantly greater right arm BMD compared with the controls but also a greater BMD of the lumbar spine, the pelvis and legs. In contrast, the low-strain, low-impact activities of keep-fit, cycling and rowing failed to benefit BMD compared with the age-matched controls. These results suggest that sporting activities involving high impact, physical contact and/or rotational forces or strains are likely to convey significant benefits not only to the loaded sites, but also to other unloaded peripheral and axial sites throughout the skeleton.

Characterization and evolution of an activator-independent methanol dehydrogenase from Cupriavidus necator N-1.

PubMed

Wu, Tung-Yun; Chen, Chang-Ting; Liu, Jessica Tse-Jin; Bogorad, Igor W; Damoiseaux, Robert; Liao, James C

2016-06-01

Methanol utilization by methylotrophic or non-methylotrophic organisms is the first step toward methanol bioconversion to higher carbon-chain chemicals. Methanol oxidation using NAD-dependent methanol dehydrogenase (Mdh) is of particular interest because it uses NAD(+) as the electron carrier. To our knowledge, only a limited number of NAD-dependent Mdhs have been reported. The most studied is the Bacillus methanolicus Mdh, which exhibits low enzyme specificity to methanol and is dependent on an endogenous activator protein (ACT). In this work, we characterized and engineered a group III NAD-dependent alcohol dehydrogenase (Mdh2) from Cupriavidus necator N-1 (previously designated as Ralstonia eutropha). This enzyme is the first NAD-dependent Mdh characterized from a Gram-negative, mesophilic, non-methylotrophic organism with a significant activity towards methanol. Interestingly, unlike previously reported Mdhs, Mdh2 does not require activation by known activators such as B. methanolicus ACT and Escherichia coli Nudix hydrolase NudF, or putative native C. necator activators in the Nudix family under mesophilic conditions. This enzyme exhibited higher or comparable activity and affinity toward methanol relative to the B. methanolicus Mdh with or without ACT in a wide range of temperatures. Furthermore, using directed molecular evolution, we engineered a variant (CT4-1) of Mdh2 that showed a 6-fold higher K cat/K m for methanol and 10-fold lower K cat/K m for n-butanol. Thus, CT4-1 represents an NAD-dependent Mdh with much improved catalytic efficiency and specificity toward methanol compared with the existing NAD-dependent Mdhs with or without ACT activation.

Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD.

PubMed

Shephard, Elizabeth; Tye, Charlotte; Ashwood, Karen L; Azadi, Bahar; Asherson, Philip; Bolton, Patrick F; McLoughlin, Grainne

2018-01-01

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

PubMed Central

Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

2015-01-01

ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology. PMID:25972560

Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls.

PubMed

Engel, K R; Obst, K; Bandelow, B; Dechent, P; Gruber, O; Zerr, I; Ulrich, K; Wedekind, D

2016-09-01

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

MicroRNA-1 and -133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex

PubMed Central

Belevych, Andriy E.; Sansom, Sarah E.; Terentyeva, Radmila; Ho, Hsiang-Ting; Nishijima, Yoshinori; Martin, Mickey M.; Jindal, Hitesh K.; Rochira, Jennifer A.; Kunitomo, Yukiko; Abdellatif, Maha; Carnes, Cynthia A.; Elton, Terry S.; Györke, Sandor; Terentyev, Dmitry

2011-01-01

In heart failure (HF), arrhythmogenic spontaneous sarcoplasmic reticulum (SR) Ca2+ release and afterdepolarizations in cardiac myocytes have been linked to abnormally high activity of ryanodine receptors (RyR2s) associated with enhanced phosphorylation of the channel. However, the specific molecular mechanisms underlying RyR2 hyperphosphorylation in HF remain poorly understood. The objective of the current study was to test the hypothesis that the enhanced expression of muscle-specific microRNAs (miRNAs) underlies the HF-related alterations in RyR2 phosphorylation in ventricular myocytes by targeting phosphatase activity localized to the RyR2. We studied hearts isolated from canines with chronic HF exhibiting increased left ventricular (LV) dimensions and decreased LV contractility. qRT-PCR revealed that the levels of miR-1 and miR-133, the most abundant muscle-specific miRNAs, were significantly increased in HF myocytes compared with controls (2- and 1.6-fold, respectively). Western blot analyses demonstrated that expression levels of the protein phosphatase 2A (PP2A) catalytic and regulatory subunits, which are putative targets of miR-133 and miR-1, were decreased in HF cells. PP2A catalytic subunit mRNAs were validated as targets of miR-133 by using luciferase reporter assays. Pharmacological inhibition of phosphatase activity increased the frequency of diastolic Ca2+ waves and afterdepolarizations in control myocytes. The decreased PP2A activity observed in HF was accompanied by enhanced Ca2+/calmodulin-dependent protein kinase (CaMKII)-mediated phosphorylation of RyR2 at sites Ser-2814 and Ser-2030 and increased frequency of diastolic Ca2+ waves and afterdepolarizations in HF myocytes compared with controls. In HF myocytes, CaMKII inhibitory peptide normalized the frequency of pro-arrhythmic spontaneous diastolic Ca2+ waves. These findings suggest that altered levels of major muscle-specific miRNAs contribute to abnormal RyR2 function in HF by depressing phosphatase activity localized to the channel, which in turn, leads to the excessive phosphorylation of RyR2s, abnormal Ca2+ cycling, and increased propensity to arrhythmogenesis. PMID:22163007

Culturally-specific physical activity measures for Native Hawaiian and Pacific Islanders.

PubMed

Moy, Karen L; Sallis, James F; Tanjasiri, Sora P

2010-05-01

Physical activity is an important contributor to the health disparities experienced by Native Hawaiian and Pacific Islander (NHPI) populations. A culturally-specific measurement instrument that minimizes interpretation bias is necessary to obtain accurate assessments of this lifestyle behavior. The purpose of this study was to 1) create two versions of the Pacific Islander Physical Activity Questionnaire (PIPAQ-short and PIPAQ-long) for United States NHPI, and 2) pilot test the PIPAQ instruments and two objective physical activity monitors to evaluate cultural-appropriateness and acceptability. Forty NHPI adults (20M, 20F) aged 21-65 years attended focus group discussions addressing cultural perspectives related to physical activity. Feedback from participants, community leaders and physical activity experts guided cultural modifications to existing questionnaires to create PIPAQ-short and PIPAQ-long with accompanying showcards. Pilot testing of both PIPAQs and two objective physical activity monitors, the Actiheart and ActiTrainer, was carried out in another sample of 32 NHPI adults (17M, 15F) aged 18-63 years. Participants were instructed to wear one monitor for ≥10 hours/day for 7 consecutive days. At the follow-up visit, participants completed PIPAQ-short and PIPAQ-long, and a written and verbal exit interview to provide feedback on both subjective and objective instruments. The majority of participants felt PIPAQ-long provided a more accurate reflection of activity levels, compared to PIPAQ-short. The Actiheart was the preferred monitor due to higher comfort and lower participant burden. Self-reported duration of physical activities was most difficult to recall, compared to activity type, frequency and intensity. Both PIPAQ instruments and the Actiheart monitor have demonstrated cultural acceptability and appropriateness for NHPI adults. Future studies will investigate the validity and reliability of both PIPAQ instruments in larger samples of NHPI adults. Hawaii Medical Journal Copyright 2010.

Solitary pulmonary nodules: Comparison of dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic first-pass contrast-enhanced MR imaging, and FDG PET/CT.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Seki, Shinichiro; Tsubakimoto, Maho; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2015-02-01

To prospectively compare the capabilities of dynamic perfusion area-detector computed tomography (CT), dynamic magnetic resonance (MR) imaging, and positron emission tomography (PET) combined with CT (PET/CT) with use of fluorine 18 fluorodeoxyglucose (FDG) for the diagnosis of solitary pulmonary nodules. The institutional review board approved this study, and written informed consent was obtained from each subject. A total of 198 consecutive patients with 218 nodules prospectively underwent dynamic perfusion area-detector CT, dynamic MR imaging, FDG PET/CT, and microbacterial and/or pathologic examinations. Nodules were classified into three groups: malignant nodules (n = 133) and benign nodules with low (n = 53) or high (n = 32) biologic activity. Total perfusion was determined with dual-input maximum slope models at area-detector CT, maximum and slope of enhancement ratio at MR imaging, and maximum standardized uptake value (SUVmax) at PET/CT. Next, all indexes for malignant and benign nodules were compared with the Tukey honest significant difference test. Then, receiver operating characteristic analysis was performed for each index. Finally, sensitivity, specificity, and accuracy were compared with the McNemar test. All indexes showed significant differences between malignant nodules and benign nodules with low biologic activity (P < .0001). The area under the receiver operating characteristic curve for total perfusion was significantly larger than that for other indexes (.0006 ≤ P ≤ .04). The specificity and accuracy of total perfusion were significantly higher than those of maximum relative enhancement ratio (specificity, P < .0001; accuracy, P < .0001), slope of enhancement ratio (specificity, P < .0001; accuracy, P < .0001), and SUVmax (specificity, P < .0001; accuracy, P < .0001). Dynamic perfusion area-detector CT is more specific and accurate than dynamic MR imaging and FDG PET/CT in the diagnosis of solitary pulmonary nodules in routine clinical practice. © RSNA, 2014.

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects.

PubMed

Yoshizane, Chiyo; Mizote, Akiko; Yamada, Mika; Arai, Norie; Arai, Shigeyuki; Maruta, Kazuhiko; Mitsuzumi, Hitoshi; Ariyasu, Toshio; Ushio, Shimpei; Fukuda, Shigeharu

2017-02-06

Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers. In a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured. Trehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion. Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

[Effect of citric acid stimulation on salivary alpha-amylase, total protein, salivary flow rate and pH value in Pi deficiency children].

PubMed

Yang, Ze-min; Chen, Long-hui; Lin, Jing; Zhang, Min; Yang, Xiao-rong; Chen, Wei-wen

2015-02-01

To compare the effect of citric acid stimulation on salivary alpha-amylase (sAA), total protein (TP), salivary flow rate, and pH value between Pi deficiency (PD) children and healthy children, thereby providing evidence for Pi controlling saliva theory. Twenty PD children were recruited, and 29 healthy children were also recruited at the same time. Saliva samples from all subjects were collected before and after citric acid stimulation. The sAA activity and amount, TP contents, salivary flow rate, and pH value were determined and compared. (1) Citric acid stimulation was able to significantly increase salivary flow rate, pH value, sAA activities, sAA specific activity and sAA amount (including glycosylated and non-glycosylated sAA amount) in healthy children (P<0.05), while it could markedly increase salivary flow rate, pH value, and glycosylated sAA levels in PD children (P<0.05); (2) Although there was no statistical difference in determined salivary indices between the two groups (P>0.05), salivary indices except salivary flow rate and glycosylated sAA levels decreased more in PD children. There was statistical difference in sAA activity ratio, sAA specific activity ratio, and the ratio of glycosylated sAA levels between PD children and healthy children (P<0.05). PD children had decreased response to citric acid stimulation.

Preclinical evaluation of posterior spine stabilization devices: can the current standards represent basic everyday life activities?

PubMed

La Barbera, Luigi; Galbusera, Fabio; Wilke, Hans-Joachim; Villa, Tomaso

2016-09-01

To discuss whether the available standard methods for preclinical evaluation of posterior spine stabilization devices can represent basic everyday life activities and how to compare the results obtained with different procedures. A comparative finite element study compared ASTM F1717 and ISO 12189 standards to validated instrumented L2-L4 segments undergoing standing, upper body flexion and extension. The internal loads on the spinal rod and the maximum stress on the implant are analysed. ISO recommended anterior support stiffness and force allow for reproducing bending moments measured in vivo on an instrumented physiological segment during upper body flexion. Despite the significance of ASTM model from an engineering point of view, the overly conservative vertebrectomy model represents an unrealistic worst case scenario. A method is proposed to determine the load to apply on assemblies with different anterior support stiffnesses to guarantee a comparable bending moment and reproduce specific everyday life activities. The study increases our awareness on the use of the current standards to achieve meaningful results easy to compare and interpret.

The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

PubMed Central

Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

2013-01-01

SUMMARY The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution. PMID:23827682

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.

Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome.

PubMed

Hanevik, Kurt; Kristoffersen, Einar; Mørch, Kristine; Rye, Kristin Paulsen; Sørnes, Steinar; Svärd, Staffan; Bruserud, Øystein; Langeland, Nina

2017-01-28

The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling. Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.

Functional neuroimaging of sex differences in autobiographical memory recall in depression.

PubMed

Young, K D; Bodurka, J; Drevets, W C

2017-11-01

Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD. Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task. The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall. The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.

Contractile function of the myocardium with prolonged hypokinesia in patients with surgical tuberculosis

NASA Technical Reports Server (NTRS)

Zakutayeva, V. P.; Matiks, N. I.

1978-01-01

The changes in the myocardial contractile function with hypokinesia in surgical tuberculosis patients are discussed. The phase nature of the changes is noted, specifically the changes in the various systoles, diastole, and other parts of the cardiac cycle. The data compare these changes during confinement in bed with no motor activity to and with a return to motor activity after leaving the in-bed regimen.

Multicentre evaluation of music perception in adult users of Advanced Bionics cochlear implants.

PubMed

Adams, Doris; Ajimsha, Khalid Mohamed; Barberá, Manuel Tomás; Gazibegovic, Dzemal; Gisbert, Javier; Gómez, Justo; Raveh, Eyal; Rocca, Christine; Romanet, Philipe; Seebens, Yvonne; Zarowski, Andrzej

2014-01-01

To document musical listening and enjoyment in recipients of Advanced Bionics cochlear implants (CIs) and to compare musical perception in those using early coding strategies with subjects using the newer HiRes and HiRes 120 strategies. A questionnaire was completed by 136 adult subjects, including questions on the ability to identify specific musical features. The subjects were in three groups: those using early coding strategies (n = 29), HiRes (n = 59), and HiRes 120 (n = 48), and results were compared with a group of 84 normally hearing (NH) subjects. Of the CI users, 79% reported listening to music. The NH group rated listening frequency and enjoyment higher than the CI users. Thirty-five users reported that they sang and this group had significantly higher overall performance. There were no significant differences in overall perception of specific musical features among the strategy groups, though some individual questions showed significantly higher performance in the HiRes 120 users. Users of current CI technology show a high level of musical appreciation, though still significantly less than NH subjects. Frequency of listening and enjoyment were significantly correlated and active participation in musical activities, specifically singing, resulted in significantly higher overall performance scores.

Geobiological Comparisons of Preservation Potential within Hypersaline Mineral-Microbe Systems

NASA Astrophysics Data System (ADS)

Perl, S. M.; Celestian, A. J.; Vaishampayan, P.; Seuylemezian, A.; Mahseredjian, T.; Baxter, B.; Corsetti, F. A.

2017-12-01

The purpose of these investigations is to show comparative measurements between known biological sources of biomarkers and biosignatures and how they can be independently verified, within instrumentation limits, by laboratory investigations analogous to future surface missions to Mars and Europa. Precipitated hypersaline mineralogy can provide a biotic record of microbial activity and habitation within evaporating lake systems. The extent of microbial preservation is a direct relationship between the magnitudes of aqueous activity post-precipitation, original or in-situ biological habitats, dissolution events due to chemical weathering, and organic matter degradation due to UV exposure and desiccation. Chemical biomarkers and physical biosignatures to be quantified and correlated based from preserved DNA as the most sensitive biomarker to more recalcitrant biomarkers such as lipids and Total Organic Carbon (TOC). Moreover the timing of cell movement during nutrient cycling within specific evaporite minerals can be associated to the formation of physical biosignatures as a function of already active and abundant biomarkers allowing for relative timelines of biogenic actions (e.g., nutrient cycling, cell division) to be correlated together. Our investigation has compared hypersaline biotic activity within different photosynthetic and chemosynthetic settings to quantify preservation and detection profiles given measured DNA as the source validation standard and micron-scale Raman measurements for specific paleoenvironmental mineral sampling.

C14 Assays and Autoradiographic Studies on the Rooster Comb

PubMed Central

Balazs, Endre A.; Szirmai, John A.; Bergendahl, Gudrun

1959-01-01

The distribution of C14 was studied in various parts of the rooster comb following treatment with testosterone. The value of gas-phase assay of C14 in tissue has been demonstrated and the results compared with those of autoradiographic studies on the same tissue. The results of these experiments showed that androgen treatment significantly increases the rate of incorporation of C14 in various parts of the comb. The specific activity of carbon in the comb, cornea, and liver differed, depending on which precursor, viz. glucose-6-C14, glucose-1-C14, and glucuronolactone-U-C14, was administered. The highest values were obtained after the administration of glucose-6-C14; glucuronolactone-U-C14 gave the lowest specific activity. The specific activity of carbon in different parts of the comb showed considerable variation. Carbon assay of serial sections of the comb cut at various planes showed that the specific activity of carbon was highest in the mucoid layer. Both C14 assays and autoradiograms indicate that C14 is also present in other parts of the comb. As seen in autoradiography, the concentration of C14 was highest in the epithelium, in the blood vessel walls, and in the avascular collagenous tissue. These results, and indications from previous studies, suggest that the high specific activity of carbon in the mucoid layer is due mainly to the presence of C14-labelled hyaluronic acid. Autoradiograms and PAS staining suggest that a significant amount of C14 is also incorporated into the glycoproteins associated with the collagen fibers. PMID:13654453

Targeted transfection increases siRNA uptake and gene silencing of primary endothelial cells in vitro--a quantitative study.

PubMed

Asgeirsdóttir, Sigridur A; Talman, Eduard G; de Graaf, Inge A; Kamps, Jan A A M; Satchell, Simon C; Mathieson, Peter W; Ruiters, Marcel H J; Molema, Grietje

2010-01-25

Applications of small-interfering RNA (siRNA) call for specific and efficient delivery of siRNA into particular cell types. We developed a novel, non-viral targeting system to deliver siRNA specifically into inflammation-activated endothelial cells. This was achieved by conjugating the cationic amphiphilic lipid SAINT to antibodies recognizing the inflammatory cell adhesion molecule E-selectin. These anti-E-selectin-SAINT lipoplexes (SAINTarg) maintained antigen recognition capacity of the parental antibody in vitro, and ex vivo in human kidney tissue slices subjected to inflammatory conditions. Regular SAINT mediated transfection resulted in efficient gene silencing in human microvascular endothelial cells (HMEC-1) and conditionally immortalized glomerular endothelial cells (ciGEnC). However, primary human umbilical vein endothelial cells (HUVEC) transfected poorly, a phenomenon that we could quantitatively correlate with a cell-type specific capacity to facilitate siRNA uptake. Importantly, SAINTarg increased siRNA uptake and transfection specificity for activated endothelial cells. Transfection with SAINTarg delivered significantly more siRNA into activated HUVEC, compared to transfection with non-targeted SAINT. The enhanced uptake of siRNA was corroborated by improved silencing of both gene- and protein expression of VE-cadherin in activated HUVEC, indicating that SAINTarg delivered functionally active siRNA into endothelial cells. The obtained results demonstrate a successful design of a small nucleotide carrier system with improved and specific siRNA delivery into otherwise difficult-to-transfect primary endothelial cells, which in addition reduced considerably the amount of siRNA needed for gene silencing. Copyright 2009 Elsevier B.V. All rights reserved.

Comparative secretome analysis of four isogenic Bacillus clausii probiotic strains

PubMed Central

2013-01-01

Background The spore-bearing alkaliphilic Bacillus species constitute a large, heterogeneous group of microorganisms, important for their ability to produce enzymes, antibodies and metabolites of potential medical use. Some Bacillus species are currently being used for manufacturing probiotic products consisting of bacterial spores, exhibiting specific features (colonization, immune-stimulation and antimicrobial activity) that can account for their claimed probiotic properties. In the present work a comparative proteomic study was performed aimed at characterizing the secretome of four closely related isogenic O/C, SIN, N/R and T B. clausii strains, already marketed in a pharmaceutical mixture as probiotics. Results Proteomic analyses revealed a high degree of concordance among the four secretomes, although some proteins exhibited considerable variations in their expression level in the four strains. Among these, some proteins with documented activity in the interaction with host cells were identified, such as the glycolytic enzyme enolase, with a putative plasminogen-binding activity, GroEL, a molecular chaperone shown to be able to bind to mucin, and flagellin protein, a structural flagella protein and a putative immunomodulation agent. Conclusion This study shows, for the first time, differences in the secretome of the OC, SIN, NR and T B. clausii strains. These differences indicate that specific secretome features characterize each of the four strains despite their genotypic similarity. This could confer to the B. clausii strains specific probiotic functions associated with the differentially expressed proteins and indicate that they can cooperate as probiotics as the secretome components of each strain could contribute to the overall activity of a mixed probiotic preparation. PMID:23816335

Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides.

PubMed

Zdzieblik, Denise; Oesser, Steffen; Gollhofer, Albert; König, Daniel

2017-06-01

The aim of the study was to evaluate the use of specific collagen peptides in reducing pain in athletes with functional knee problems during sport. Athletic subjects (n = 139) with functional knee pain ingested 5 g of bioactive collagen peptides (BCP) or a placebo per day for 12 weeks. The primary outcome of the study was a change in pain intensity during activity, which was evaluated by the participants and the attending physicians using a visual analogue scale (VAS). As secondary endpoints, pain intensity under resting conditions, the range of motion of the knee joint, and the use of additional therapeutic options were assessed. The results revealed a statistically significant improvement in activity-related pain intensity in the verum group compared with placebo. (ΔVAS BCP = 19.5 ± 2.4; ΔVAS Placebo = 13.9 ± 2.1; p = 0.046). The results were confirmed by the physician's assessment. (ΔVAS BCP = 16.7 ± 1.8; ΔVAS Placebo = 12.2 ± 1.8; p = 0.021). Pain under resting conditions was also improved, but no significance compared with placebo was detected (ΔVAS BCP = 10.2 ± 18.4; ΔVAS Placebo = 7.4 ± 15.2; p = 0.209). Due to the high joint mobility at baseline, no significant changes of this parameter could be detected. The use of additional treatment options was significantly reduced after BCP intake. The study demonstrated that the supplementation of specific collagen peptides in young adults with functional knee problems led to a statistically significant improvement of activity-related joint pain.

The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells

PubMed Central

Crozat, Karine; Guiton, Rachel; Contreras, Vanessa; Feuillet, Vincent; Dutertre, Charles-Antoine; Ventre, Erwan; Vu Manh, Thien-Phong; Baranek, Thomas; Storset, Anne K.; Marvel, Jacqueline; Boudinot, Pierre; Hosmalin, Anne; Schwartz-Cornil, Isabelle

2010-01-01

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria. PMID:20479118

Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome.

PubMed

Denier, Colette C; Brisson-Lougarre, Andrée A; Biasini, Ghislaine G; Grozdea, Jean J; Fournier, Didier D

2002-01-01

In humans, there are four alkaline phosphatases, and each form exhibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnant with a trisomy 21 fetus (Down's syndrome) displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases) were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate), allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60-80% of activity. Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome.

Processing of voices in deafness rehabilitation by auditory brainstem implant.

PubMed

Coez, Arnaud; Zilbovicius, Monica; Ferrary, Evelyne; Bouccara, Didier; Mosnier, Isabelle; Ambert-Dahan, Emmanuèle; Kalamarides, Michel; Bizaguet, Eric; Syrota, André; Samson, Yves; Sterkers, Olivier

2009-10-01

The superior temporal sulcus (STS) is specifically involved in processing the human voice. Profound acquired deafness by post-meningitis ossified cochlea and by bilateral vestibular schwannoma in neurofibromatosis type 2 patients are two indications for auditory brainstem implantation (ABI). In order to objectively measure the cortical voice processing of a group of ABI patients, we studied the activation of the human temporal voice areas (TVA) by PET H(2)(15)O, performed in a group of implanted deaf adults (n=7) with more than two years of auditory brainstem implant experience, with an intelligibility score average of 17%+/-17 [mean+/-SD]. Relative cerebral blood flow (rCBF) was measured in the three following conditions: during silence, while passive listening to human voice, and to non-voice stimuli. Compared to silence, the activations induced by voice and non-voice stimuli were bilaterally located in the superior temporal regions. However, compared to non-voice stimuli, the voice stimuli did not induce specific supplementary activation of the TVA along the STS. The comparison of ABI group with a normal-hearing controls group (n=7) showed that TVA activations were significantly enhanced among controls group. ABI allowed the transmission of sound stimuli to temporal brain regions but lacked transmitting the specific cues of the human voice to the TVA. Moreover, among groups, during silent condition, brain visual regions showed higher rCBF in ABI group, although temporal brain regions had higher rCBF in the controls group. ABI patients had consequently developed enhanced visual strategies to keep interacting with their environment.

The effect of Pediococcus acidilactici bacteria used as probiotic supplement on the growth and non-specific immune responses of green terror, Aequidens rivulatus.

PubMed

Neissi, Alireza; Rafiee, Gholamreza; Nematollahi, Mohammadali; Safari, Omid

2013-12-01

A 56-day feeding trial was conducted on a species of ornamental fish called green terror (Aequidens rivulatus) (0.388 ± 0.0021 g) to assess the effect of probiotic bacteria, Pediococcus acidilactici on the growth indices and innate immune response. The fish were randomly allocated into 9 oval tanks (120 l) at a density of 60 fish per tank. The experimental diets were comprised of the control (C), C complemented with fish oil (O) and the probiotic and fish oil (PA) and fed ad lib twice a day. The growth indices (specific growth rate (SGR), feed conversion ratio (FCR) and immunological indices of fish fed the diets including lysozyme activity, total immunoglobulin and alternative complement activity were measured. The Fish fed with the diet containing P. acidilactici (PA) displayed significantly (P < 0.05) higher final weight (3.25 ± 0.065 g), weight gain (830.94 ± 9.46%), SGR (3.53 ± 0.02%/day) and lower FCR (1.45 ± 0.011) compared to those of other experimental diets. Total immunoglobulin (10.05 ± 0.12 μg/ml), lysozyme activity (4.08 ± 0.85 μg/ml) and alternative complement activity (2.65 ± 0.12 U/ml) in the serum of PA fed fish showed significant compared to other treatments (P < 0.05). The results showed positive effects of P. acidilactici as a potent probiotic on growth indices and non-specific immune system of green terror. Copyright © 2013 Elsevier Ltd. All rights reserved.

Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.

PubMed

Silverman, Daniel H S; Dy, Christine J; Castellon, Steven A; Lai, Jasmine; Pio, Betty S; Abraham, Laura; Waddell, Kari; Petersen, Laura; Phelps, Michael E; Ganz, Patricia A

2007-07-01

To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer. Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis. During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects. Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy.

Is active participation in specific sport activities linked with back pain?

PubMed

Mogensen, A M; Gausel, A M; Wedderkopp, N; Kjaer, P; Leboeuf-Yde, C

2007-12-01

A cross-sectional survey of 439 children/adolescents aged 12-13, living in Odense, Denmark, in the year 2001. To investigate (1) if there is any difference in back pain reporting among those practising specific sports as compared with non-performers and (2) if there is an association between specific kinds of sports and self-reported back problems. Back pain is a common complaint in young people and physical inactivity is generally thought to contribute to this. However, some specific sport activities may be detrimental or beneficial to the spine. Information was collected through a semi-structured interview, a physical examination, and a questionnaire. Associations for back pain, low back pain, mid back pain and neck pain in the preceding month were investigated in relation to specific sports. Associations were controlled for body mass index, puberty stage and sex. There was no association between back problems and the practising of sports in general. However, some sports were either positively or negatively associated with back pain. Taking into account the relatively small subgroups and multiple testing, some sports seem to be potentially harmful or beneficial. These sports should be investigated in proper longitudinal study designs, in relation to their effects on back problems in the young.

Tissue- and Cell-Specific Cytokinin Activity in Populus × canescens Monitored by ARR5::GUS Reporter Lines in Summer and Winter.

PubMed

Paul, Shanty; Wildhagen, Henning; Janz, Dennis; Teichmann, Thomas; Hänsch, Robert; Polle, Andrea

2016-01-01

Cytokinins play an important role in vascular development. But knowledge on the cellular localization of this growth hormone in the stem and other organs of woody plants is lacking. The main focus of this study was to investigate the occurrence and cellular localization of active cytokinins in leaves, roots, and along the stem of Populus × canescens and to find out how the pattern is changed between summer and winter. An ARR5::GUS reporter construct was used to monitor distribution of active cytokinins in different tissues of transgenic poplar lines. Three transgenic lines tested under outdoor conditions showed no influence of ARR5::GUS reporter construct on the growth performance compared with the wild-type, but one line lost the reporter activity. ARR5::GUS activity indicated changes in the tissue- and cell type-specific pattern of cytokinin activity during dormancy compared with the growth phase. ARR5::GUS activity, which was present in the root tips in the growing season, disappeared in winter. In the stem apex ground tissue, ARR5::GUS activity was higher in winter than in summer. Immature leaves from tissue-culture grown plants showed inducible ARR5::GUS activity. Leaf primordia in summer showed ARR5::GUS activity, but not the expanded leaves of outdoor plants or leaf primordia in winter. In stem cross sections, the most prominent ARR5::GUS activity was detected in the cortex region and in the rays of bark in summer and in winter. In the cambial zone the ARR5::GUS activity was more pronounced in the dormant than in growth phase. The pith and the ray cells adjacent to the vessels also displayed ARR5::GUS activity. In silico analyses of the tissue-specific expression patterns of the whole PtRR type-A family of poplar showed that PtRR10, the closest ortholog to the Arabidopsis ARR5 gene, was usually the most highly expressed gene in all tissues. In conclusion, gene expression and tissue-localization indicate high activity of cytokinins not only in summer, but also in winter. The presence of the signal in meristematic tissues supports their role in meristem maintenance. The reporter lines will be useful to study the involvement of cytokinins in acclimation of poplar growth to stress.

Accelerometer-determined physical activity and all-cause mortality in a national prospective cohort study of hypertensive adults.

PubMed

Loprinzi, Paul D

2016-05-01

Research in the general population suggests an inverse association between physical activity and all-cause mortality. Less research on this topic has been conducted among hypertensive adults, but the limited studies also suggest an inverse association between physical activity and all-cause mortality among hypertensive adults. At this point, sex-specific differences are not well understood, and all of the physical activity-mortality studies among hypertensive adults have employed a self-report measure of physical activity. Therefore, the purpose of this study was to examine the sex-specific association between objectively measured physical activity and all-cause mortality among a national sample of hypertensive adults. Data from the 2003 to 2006 National Health and Nutrition Examination Survey, with follow-up through 2011, were employed. Hypertension status was defined using measured blood pressure and use of blood pressure-lowering medication. Physical activity was assessed via accelerometry. After adjustments, for every 60-min increase in physical activity, hypertensive adults had a 19% (hazard rate = 0.81; 95% confidence interval: 0.72-0.91) reduced risk of all-cause mortality. There was also evidence of a dose-response relationship. Compared with those in the lowest tertile, those in the middle and upper tertiles had a 31 and 42% reduced all-cause mortality risk, respectively. There was no evidence of a sex-specific interaction effect. Among hypertensive adults, objectively measured physical activity is associated with all-cause mortality risk in a dose-response manner.

Shifting wavelengths of ultraweak photon emissions from dying melanoma cells: their chemical enhancement and blocking are predicted by Cosic's theory of resonant recognition model for macromolecules.

PubMed

Dotta, Blake T; Murugan, Nirosha J; Karbowski, Lukasz M; Lafrenie, Robert M; Persinger, Michael A

2014-02-01

During the first 24 h after removal from incubation, melanoma cells in culture displayed reliable increases in emissions of photons of specific wavelengths during discrete portions of this interval. Applications of specific filters revealed marked and protracted increases in infrared (950 nm) photons about 7 h after removal followed 3 h later by marked and protracted increases in near ultraviolet (370 nm) photon emissions. Specific wavelengths within the visible (400 to 800 nm) peaked 12 to 24 h later. Specific activators or inhibitors for specific wavelengths based upon Cosic's resonant recognition model elicited either enhancement or diminishment of photons at the specific wavelength as predicted. Inhibitors or activators predicted for other wavelengths, even within 10 nm, were less or not effective. There is now evidence for quantitative coupling between the wavelength of photon emissions and intrinsic cellular chemistry. The results are consistent with initial activation of signaling molecules associated with infrared followed about 3 h later by growth and protein-structural factors associated with ultraviolet. The greater-than-expected photon counts compared with raw measures through the various filters, which also function as reflective material to other photons, suggest that photons of different wavelengths might be self-stimulatory and could play a significant role in cell-to-cell communication.

Physical activity and mental health in women with Polycystic Ovary Syndrome

PubMed Central

2014-01-01

Background Physical activity is prescribed as a component of primary management for Polycystic Ovary Syndrome (PCOS). This study investigates the association between physical activity and mental health as well as the exercise barriers, motivators and support providers for younger women with and without PCOS to assist in physical activity uptake and prescription for these women. Methods Women aged 18-50 years with (n = 153) and without PCOS (n = 64) completed a questionnaire at one time point. The questionnaire included the Hospital Anxiety and Depression Scale and a survey regarding levels of physical activity, physical activity barriers, motivators and supports. A MANCOVA assessed associations between physical activity, PCOS and mental health (specifically depression and anxiety). Descriptive and Chi square goodness of fit statistics assessed the differences in perceived barriers, motivators and support providers amongst women with and without PCOS. Results Women with PCOS displayed higher severity of depression (F(1,210) = 8.32, p = 0.004) and anxiety (F(1,210) = 17.37, p < 0.001) symptoms compared to controls. Overall, for physically active women, depression was significantly less severe than in their inactive counterparts (F(2,210) = 13.62, p < 0.001). There were no differences in anxiety by physical activity status and no interaction effects between PCOS and activity status for depression or anxiety. Women with PCOS were more likely to report a lack of confidence about maintaining physical activity (Χ 2  = 3.65; p = 0.046), fear of injury (Χ 2  = 4.08; p = 0.043) and physical limitations (Χ 2  = 11.92; p = 0.001) as barriers to physical activity and were more likely to be motivated to be active to control a medical condition (Χ 2  = 7.48; p = 0.006). Women with PCOS identified more sources of support compared to women without PCOS. Conclusions Physical activity is associated with lower depression in women with PCOS and differences exist in the self-reported physical activity barriers, motivators and support providers, compared to controls. Being more active may offer mental health benefits in managing PCOS. Prescribing physical activity to women with PCOS should be individualized and consider both common and PCOS-specific barriers and motivators for successful engagement. PMID:24674140

Physical activity and mental health in women with polycystic ovary syndrome.

PubMed

Banting, Lauren K; Gibson-Helm, Melanie; Polman, Remco; Teede, Helena J; Stepto, Nigel K

2014-03-27

Physical activity is prescribed as a component of primary management for Polycystic Ovary Syndrome (PCOS). This study investigates the association between physical activity and mental health as well as the exercise barriers, motivators and support providers for younger women with and without PCOS to assist in physical activity uptake and prescription for these women. Women aged 18-50 years with (n = 153) and without PCOS (n = 64) completed a questionnaire at one time point. The questionnaire included the Hospital Anxiety and Depression Scale and a survey regarding levels of physical activity, physical activity barriers, motivators and supports. A MANCOVA assessed associations between physical activity, PCOS and mental health (specifically depression and anxiety). Descriptive and Chi square goodness of fit statistics assessed the differences in perceived barriers, motivators and support providers amongst women with and without PCOS. Women with PCOS displayed higher severity of depression (F(1,210) = 8.32, p = 0.004) and anxiety (F(1,210) = 17.37, p < 0.001) symptoms compared to controls. Overall, for physically active women, depression was significantly less severe than in their inactive counterparts (F(2,210) = 13.62, p < 0.001). There were no differences in anxiety by physical activity status and no interaction effects between PCOS and activity status for depression or anxiety. Women with PCOS were more likely to report a lack of confidence about maintaining physical activity (Χ2 = 3.65; p = 0.046), fear of injury (Χ2 = 4.08; p = 0.043) and physical limitations (Χ2 = 11.92; p = 0.001) as barriers to physical activity and were more likely to be motivated to be active to control a medical condition (Χ2 = 7.48; p = 0.006). Women with PCOS identified more sources of support compared to women without PCOS. Physical activity is associated with lower depression in women with PCOS and differences exist in the self-reported physical activity barriers, motivators and support providers, compared to controls. Being more active may offer mental health benefits in managing PCOS. Prescribing physical activity to women with PCOS should be individualized and consider both common and PCOS-specific barriers and motivators for successful engagement.

Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity.

PubMed

Würtzen, Peter Adler; Lund, Lise; Lund, Gitte; Holm, Jens; Millner, Anders; Henmar, Helene

2007-01-01

In Europe, specific immunotherapy is currently conducted with vaccines containing allergen preparations based on intact extracts. In addition to this, chemically modified allergen extracts (allergoids) are used for specific allergy treatment. Reduced allergenicity and thereby reduced risk of side effects in combination with retained ability to activate T cells and induce protective allergen-specific antibody responses has been claimed for allergoids. In the current study, we compared intact allergen extracts and allergoids with respect to allergenicity and immunogenicity. The immunological response to birch allergen extract, alum-adsorbed extract, birch allergoid and alum-adsorbed allergoid was investigated in vitro in human basophil histamine release assay and by stimulation of human allergen-specific T cell lines. In vivo, Bet v 1-specific IgG titers in mice were determined after repetitive immunizations. In all patients tested (n = 8), allergoid stimulations led to reduced histamine release compared to the intact allergen extract. However, the allergoid preparations were not recognized by Bet v 1-specific T cell lines (n = 7), which responded strongly to the intact allergen extract. Mouse immunizations showed a clearly reduced IgG induction by allergoids and a strongly potentiating effect of the alum adjuvant. Optimal IgG titers were obtained after 3 immunizations with intact allergen extracts, while 5 immunizations were needed to obtain maximal response to the allergoid. The reduced histamine release observed for allergoid preparations may be at the expense of immunological efficacy because the chemical modifications lead to a clear reduction in T cell activation and the ability to induce allergen-specific IgG antibody responses. Copyright 2007 S. Karger AG, Basel.

Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

PubMed

Levy, Robert; Khokhlov, Alexander; Kopenkin, Sergey; Bart, Boris; Ermolova, Tatiana; Kantemirova, Raiasa; Mazurov, Vadim; Bell, Marjorie; Caldron, Paul; Pillai, Lakshmi; Burnett, Bruce

2010-12-01

twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and symptoms of OA of the knee. Detailed analyses of subject subsets demonstrated distinct trends in favor of flavocoxid for specific groups of subjects.

Supermacroporous cryogel matrix for integrated protein isolation. Immobilized metal affinity chromatographic purification of urokinase from cell culture broth of a human kidney cell line.

PubMed

Kumar, Ashok; Bansal, Vibha; Andersson, Jonatan; Roychoudhury, Pradip K; Mattiasson, Bo

2006-01-20

A new type of supermacroporous, monolithic, cryogel affinity adsorbent was developed, allowing the specific capture of urokinase from conditioned media of human fibrosarcoma cell line HT1080. The affinity adsorbent was designed with the objective of using it as a capture column in an integrated perfusion/protein separation bioreactor setup. A comparative study between the utility of this novel cryogel based matrix and the conventional Sepharose based affinity matrix for the continuous capture of urokinase in an integrated bioreactor system was performed. Cu(II)-ion was coupled to epoxy activated polyacrylamide cryogel and Sepharose using iminodiacetic acid (IDA) as the chelating ligand. About 27-fold purification of urokinase from the conditioned culture media was achieved with Cu(II)-IDA-polyacrylamide cryogel column giving specific activity of about 814 Plough units (PU)/mg protein and enzyme yields of about 80%. High yields (95%) were obtained with Cu(II)-IDA-Sepharose column by virtue of its high binding capacity. However, the adsorbent showed lower selectivity as compared to cryogel matrix giving specific activity of 161 PU/mg protein and purification factor of 5.3. The high porosity, selectivity and reasonably good binding capacity of Cu(II)-IDA-polyacrylamide cryogel column make it a promising option for use as a protein capture column in integrated perfusion/separation processes. The urokinase peak pool from Cu(II)-IDA-polyacrylamide cryogel column could be further resolved into separate fractions for high and low molecular weight forms of urokinase by gel filtration chromatography on Sephacryl S-200. The selectivity of the cryogel based IMAC matrix for urokinase was found to be higher as compared to that of Cu(II)-IDA-Sepharose column.

Prolonged treatment of porcine pulmonary artery with nitric oxide decreases cGMP sensitivity and cGMP-dependent protein kinase specific activity

PubMed Central

Perkins, William J.; Warner, David O.; Jones, Keith A.

2009-01-01

A cultured porcine pulmonary artery (PA) model was used to examine the effects of prolonged nitric oxide (NO) treatment on the response to acutely applied NO, cGMP analog, or atrial natriuretic peptide (ANP). Twenty-four-hour treatment with the NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) resulted in >10-fold decrease in the response to acutely applied DETA-NO. In parallel with this, the relaxant response to acutely applied cGMP analog, β-phenyl-1,N2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-PET-cGMPS), and ANP decreased. The reduction in ANP responsiveness in PA was not associated with a reduction in cGMP levels evoked by 10−6 M ANP. Twenty-four hours in culture and treatment with DETA-NO decreased total cGMP-dependent protein kinase (cGKI) mRNA level compared with that in freshly prepared PA (1.05 ± 0.12, 0.42 ± 0.08, and 0.11 ± 0.01 amol/μg, respectively). Total cGKI protein levels were decreased to a lesser extent by 24 h in culture and further decreased by 24-h DETA-NO treatment compared with that in freshly prepared PA (361 ± 33, 272 ± 20, and 238 ± 25 ng/mg total protein, respectively). Maximal cGMP-stimulated phosphotransferase activity was reduced in 24-h cultured and DETA-NO-treated PA (986 ± 84, 815 ± 81, and 549 ± 78 pmol Pi·min−1·mg soluble protein−1), but the cGMP concentration resulting in 50% of maximal phosphotransferase activity was not. cGKI specific activity (maximal cGMP-activated phosphotransferase activity/ng cGKI) was significantly reduced in PA treated with DETA-NO for 24 h compared with freshly prepared and 24-h cultured PA (1.95 ± 0.22, 2.64 ± 0.25, and 2.85 ± 0.28 pmol Pi·min−1·ng cGKI−1, respectively). We conclude that prolonged NO treatment induces decreased acute NO responsiveness in PA in part by decreasing cGMP sensitivity. It does so by decreasing both cGKI expression and cGKI specific activity. PMID:18952758

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.

Prolonged activation EEG differentiates dementia with and without delirium in frail elderly patients.

PubMed

Thomas, C; Hestermann, U; Walther, S; Pfueller, U; Hack, M; Oster, P; Mundt, C; Weisbrod, M

2008-02-01

Delirium in the elderly results in increased morbidity, mortality and functional decline. Delirium is underdiagnosed, particularly in dementia. To increase diagnostic accuracy, we investigated whether maintenance of activation assessed by EEG discriminates delirium in association with dementia (D+D) from dementia without delirium (DP) and cognitively unimpaired elderly subjects (CU). Routine and quantitative EEG (rEEG/qEEG) with additional prolonged activation (3 min eyes open period) were evaluated in hospitalised elderly patients with acute geriatric disease. Patients were assigned post hoc to three comparable groups (D+D/DP/CU) by expert consensus based on DSM-IV criteria. Dementia diagnosis was confirmed using cognitive and functional tests and caregiver rating (IQCODE, Informed Questionnaire of Cognitive Decline in the Elderly). While rEEG at rest showed low accuracy for a diagnosis of delirium, qEEG in DP and CU revealed a specific activation pattern of high significance found to be absent in the D+D group. Stepwise logistic regression confirmed that differentiation of D+D from DP was best resolved using activated upper alpha and delta power density which, compared with rEEG, enabled an 11% increase in diagnostic correctness to 83%, resulting in 67% sensitivity and 91% specificity. Among frail CU and D+D subjects, almost 90% were correctly classified. Dementia associated with delirium can be discriminated reliably from dementia alone in a meaningful clinical setting. Thus EEG evaluation in chronic encephalopathy should be optimised by a simple activation task and spectral analysis, particularly in the elderly with dementia.

Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association With Overall Survival.

PubMed

Antonarakis, Emmanuel S; Small, Eric J; Petrylak, Daniel; Quinn, David I; Kibel, Adam S; Chang, Nancy; Dearstyne, Erica; Harmon, Matthew; Campogan, Dwayne; Haynes, Heather; Vu, Tuyen; Sheikh, Nadeem A; Drake, Charles G

2018-06-01

Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP). PAP- and PA2024-specific proliferative and cytolytic responses were characterized to delineate sipuleucel-T-induced immune responses. To quantify potential cytotoxic T lymphocyte (CTL) activity, cell-surface CD107a expression on PAP- or PA2024-specific CD8+ T cells was measured in sipuleucel-T-treated patient and healthy volunteer samples. Increased PA2024-specific CD4+ (p=0.030) and CD8+ (p=0.052) T-cell proliferation from baseline to week 6 was observed (N=14) post-sipuleucel-T, with greater magnitude of PA2024-specific responses compared to PAP. PAP- and PA2024-CTL activity (CD107a positivity) significantly increased at weeks 6 and 26 after sipuleucel-T treatment (p<0.0001; N=22). At 26 weeks post-sipuleucel-T, OS correlated with the magnitude of PAP (Pearson's R, 0.52; p=0.013) or PA2024 (Pearson's R, 0.67; p=0.0006) CTL activity. Higher PA2024-CTL activity at week 26 was significantly associated with longer OS using tertile analysis (p=0.0005; N=22), with PA2024 responses correlating with PAP responses at week 26 (R=0.90; p=1.53E -08 ). This study is the first to report PAP-specific CD8+ T-cell responses elicited by sipuleucel-T treatment. Increased and persistent potential PA2024-specific CTL activity correlated with PAP-specific CTL activity and associated with improved OS following sipuleucel-T treatment. Copyright ©2018, American Association for Cancer Research.

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

Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

PubMed

Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

2018-05-09

Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Tobacco Alkaloids and Tobacco-specific Nitrosamines in Dust from Homes of Smokeless Tobacco Users, Active Smokers, and Non-tobacco Users

PubMed Central

Whitehead, Todd P.; Havel, Christopher; Metayer, Catherine; Benowitz, Neal L.; Jacob, Peyton

2016-01-01

Smokeless tobacco products, such as moist snuff or chewing tobacco, contain many of the same carcinogens as tobacco smoke; however the impact on children of indirect exposure to tobacco constituents via parental smokeless tobacco use is unknown. As part of the California Childhood Leukemia Study, dust samples were collected from 6 homes occupied by smokeless tobacco users, 6 homes occupied by active smokers, and 20 tobacco-free homes. To assess children’s potential for exposure to tobacco constituents, vacuum-dust concentrations of five tobacco-specific nitrosamines, including N′-nitrosonornicotine [NNN] and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], as well as six tobacco alkaloids, including nicotine and myosmine were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We used generalized estimating equations derived from a multivariable marginal model to compare levels of tobacco constituents between groups, after adjusting for a history of parental smoking, income, home construction date, and mother’s age and race/ethnicity. The ratio of myosmine:nicotine was used as a novel indicator of the source of tobacco contamination, distinguishing between smokeless tobacco products and tobacco smoke. Median dust concentrations of NNN and NNK were significantly greater in homes with smokeless tobacco users compared to tobacco-free homes. In multivariable models, concentrations of NNN and NNK were 4.8-fold and 6.9-fold higher in homes with smokeless tobacco users compared to tobacco-free homes. Median myosmine:nicotine ratios were lower in homes with smokeless tobacco users (1.8%) compared to homes of active smokers (7.7%), confirming that cigarette smoke was not the predominant source of tobacco constituents in homes with smokeless tobacco users. Children living with smokeless tobacco users may be exposed to carcinogenic tobacco-specific nitrosamines via contact with contaminated dust and household surfaces. PMID:25794360

A social ecological assessment of physical activity among urban adolescents.

PubMed

Yan, Alice Fang; Voorhees, Carolyn C; Beck, Kenneth H; Wang, Min Qi

2014-05-01

To examine the physical, social and temporal contexts of physical activity, as well as sex variations of the associations among 314 urban adolescents. Three-day physical activity recall measured contextual information of physical activities. Logistic regressions and generalized estimating equation models examined associations among physical activity types and contexts, and sex differences. Active transportation was the most common physical activity. Home/neighborhood and school were the most common physical activity locations. School was the main location for organized physical activity. Boys spent more time on recreational physical activity, regardless of the social context, compared to girls. The average physical activity level was significantly lower for girls than for boys after school. Physical activity promotion interventions need to target physical activity environments and social contexts in a sex-specific manner.

Humoral and cellular immunity in cosmonauts after the ISS missions

NASA Astrophysics Data System (ADS)

Rykova, M. P.; Antropova, E. N.; Larina, I. M.; Morukov, B. V.

Spaceflight effects on the immune system were studied in 30 cosmonauts flown onto the International Space Station (ISS) for long- (125-195 d, n=15) and short-term (8-10 d, n=15) missions. Immunological investigations before launch and after landing were performed by using methods for quantitative and functional evaluation of the immunologically competent cells. Specific assays include: peripheral leukocyte distribution, natural killer (NK) cell cytotoxic activity, phagocytic activity of monocytes and granulocytes, proliferation of T-cells in response to a mitogen, levels of immunoglobulins IgA, IgM, IgG, virus-specific antibody and cytokine in serum. It was noticed that after long-term spaceflights the percentage of NK (CD3-/CD16+/CD56+) cells was significantly reduced compared with pre-flight data (p<0.05) and NK activity was suppressed by 20-85% as compared with pre-flight data in 12 out of 15 cosmonauts. T-lymphocyte activity was decreased by 25-39% as compared with pre-flight data in 5 out of 13 cosmonauts. However, the relative number of CD3+, CD4+ and CD8+ T-cells did not change. The functional activity of NK and T-cells decreased in some of the cosmonauts after short-term missions. On the other hand, a moderate trend upward of NK cytotoxic activity and proliferative activity of T-cells was observed in some individuals. Concentrations immunoglobulins (IgA, IgM, IgG) and levels of M and G antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus type 6 (HV6) in serum did not reveal significant changes after long- and short-term flights. Concentrations of cytokines (IL- 1β, IL-2, IL-4 and TNF- α) in serum changed in an apparently random manner as compared with values before long- and short-term missions. Despite the fact that many improvements have been made to the living conditions of aboard the ISS our investigations demonstrate the remarkable depression of the immunological function after the ISS missions. These results suggest that the clinical health risk (related to immune dysfunction) will occur during exploration class missions.

Activity-induced regulation of myosin isoform distribution - Comparison of two contractile activity programs

NASA Technical Reports Server (NTRS)

Diffee, Gary M.; Caiozzo, Vince J.; Mccue, Samuel A.; Herrick, Robert E.; Baldwin, Kenneth M.

1993-01-01

This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.

Auditory Responses and Stimulus-Specific Adaptation in Rat Auditory Cortex are Preserved Across NREM and REM Sleep

PubMed Central

Nir, Yuval; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Banks, Matthew I.; Tononi, Giulio

2015-01-01

Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic “gate,” which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13–20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas. PMID:24323498

Shared and disorder-specific task-positive and default mode network dysfunctions during sustained attention in paediatric Attention-Deficit/Hyperactivity Disorder and obsessive/compulsive disorder.

PubMed

Norman, Luke J; Carlisi, Christina O; Christakou, Anastasia; Cubillo, Ana; Murphy, Clodagh M; Chantiluke, Kaylita; Simmons, Andrew; Giampietro, Vincent; Brammer, Michael; Mataix-Cols, David; Rubia, Katya

2017-01-01

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18 years completed a functional magnetic resonance imaging (fMRI) version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG). ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns.

The sex-specific internal and external demands imposed on players during Ultimate Frisbee game-play.

PubMed

Madueno, Maria C; Kean, Crystal O; Scanlan, Aaron T

2017-11-01

Despite the growing popularity of Ultimate Frisbee (UF) across sexes, the game demands imposed on players have been predominately examined in males. This study aimed to compare the internal and external demands of UF game-play in males and females. Male (N.=10) and female (N.=10) recreational UF players competed in separate sex-specific, indoor UF games. Internal responses (blood lactate concentration [BLa-], rating of perceived exertion [RPE], and heart rate [HR]) and external responses (direction-specific and total relative PlayerLoad™ [PL], and estimated equivalent distance [EED]) were measured. Data were analyzed using mixed ANOVAs with Cohen's effect sizes (d). During male game-play, significantly (P<0.01) higher BLa- (d=1.30, large), HR (d=0.40, small), PL (d=0.80-1.24, moderate-large), and EED (d=0.93, moderate) were apparent during the first half compared to the second half in males. During female game-play, a significantly (P<0.001) larger RPE (d=0.93, moderate) was evident during the second compared to the first half. In addition, females exhibited significantly (P<0.05) lower BLa- (d=1.43, large) in the first half and higher medio-lateral PL (d=1.10, moderate) in the second half compared to males. While similar global responses were observed between sexes across UF game-play, males experienced greater declines in physiological intensity and multi-directional activity than females. These data indicate overlap in game demands and training recommendations across sexes, with activity maintenance a focus, particularly in males.

Electromyography of the quadriceps in patellofemoral pain with patellar subluxation.

PubMed

Mohr, Karen J; Kvitne, Ronald S; Pink, Marilyn M; Fideler, Bradley; Perry, Jacquelin

2003-10-01

This study compared muscle activity and timing of gait phases during functional activities in 13 subjects with patellofemoral pain associated with lateral subluxation and in 11 subjects with healthy knees. Fine wire electromyography recorded activity in the vastus lateralis and vastus medialis oblique during walking and ascending and descending stairs. Subjects were filmed to divide the activities into phases and determine timing. The vastus medialis oblique and vastus lateralis had similar patterns during all activities. Subjects with patellofemoral pain had significantly increased activity in the vastus medialis oblique and vastus lateralis compared with the healthy subjects during the most demanding phases of the gait cycle, suggesting a generalized quadriceps weakness in the patients with patellofemoral pain. Timing differences were seen in walking and stair ascending with the subjects with patellofemoral pain spending significantly more time in stance compared with the healthy subjects. This may be an attempt to reduce the load on weak quadriceps. These data reflect a generalized quadriceps muscle weakness, rather than the prevailing theory of quadriceps muscle imbalance as an etiology of patellofemoral pain. Therefore, we support the practice of strengthening the entire quadriceps muscle group, rather than attempting to specifically target the vastus medialis oblique.

Does Shape Discrimination by the Mouth Activate the Parietal and Occipital Lobes? – Near-Infrared Spectroscopy Study

PubMed Central

Kagawa, Tomonori; Narita, Noriyuki; Iwaki, Sunao; Kawasaki, Shingo; Kamiya, Kazunobu; Minakuchi, Shunsuke

2014-01-01

A cross-modal association between somatosensory tactile sensation and parietal and occipital activities during Braille reading was initially discovered in tests with blind subjects, with sighted and blindfolded healthy subjects used as controls. However, the neural background of oral stereognosis remains unclear. In the present study, we investigated whether the parietal and occipital cortices are activated during shape discrimination by the mouth using functional near-infrared spectroscopy (fNIRS). Following presentation of the test piece shape, a sham discrimination trial without the test pieces induced posterior parietal lobe (BA7), extrastriate cortex (BA18, BA19), and striate cortex (BA17) activation as compared with the rest session, while shape discrimination of the test pieces markedly activated those areas as compared with the rest session. Furthermore, shape discrimination of the test pieces specifically activated the posterior parietal cortex (precuneus/BA7), extrastriate cortex (BA18, 19), and striate cortex (BA17), as compared with sham sessions without a test piece. We concluded that oral tactile sensation is recognized through tactile/visual cross-modal substrates in the parietal and occipital cortices during shape discrimination by the mouth. PMID:25299397

Does shape discrimination by the mouth activate the parietal and occipital lobes? - near-infrared spectroscopy study.

PubMed

Kagawa, Tomonori; Narita, Noriyuki; Iwaki, Sunao; Kawasaki, Shingo; Kamiya, Kazunobu; Minakuchi, Shunsuke

2014-01-01

A cross-modal association between somatosensory tactile sensation and parietal and occipital activities during Braille reading was initially discovered in tests with blind subjects, with sighted and blindfolded healthy subjects used as controls. However, the neural background of oral stereognosis remains unclear. In the present study, we investigated whether the parietal and occipital cortices are activated during shape discrimination by the mouth using functional near-infrared spectroscopy (fNIRS). Following presentation of the test piece shape, a sham discrimination trial without the test pieces induced posterior parietal lobe (BA7), extrastriate cortex (BA18, BA19), and striate cortex (BA17) activation as compared with the rest session, while shape discrimination of the test pieces markedly activated those areas as compared with the rest session. Furthermore, shape discrimination of the test pieces specifically activated the posterior parietal cortex (precuneus/BA7), extrastriate cortex (BA18, 19), and striate cortex (BA17), as compared with sham sessions without a test piece. We concluded that oral tactile sensation is recognized through tactile/visual cross-modal substrates in the parietal and occipital cortices during shape discrimination by the mouth.

Nuclear Receptor CAR Specifically Activates the Two-Pore K+ Channel Kcnk1 Gene in Male Mouse Livers, Which Attenuates Phenobarbital-Induced Hepatic Hyperplasia

PubMed Central

Negishi, Masahiko

2013-01-01

KCNK1, a member of the family of two-pore K+ ion channels, is specifically induced in the livers of male mice after phenobarbital treatment. Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital-inducible antihyperplasia factor. Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (−2441/−2345) within the Kcnk1 promoter. This binding is observed in the livers of male mice, but not in the livers of female mice and requires the pituitary gland, because hypophysectomy abrogates it. Hyperplasia further progressed in the livers of Kcnk1 −/− male mice compared with those of Kcnk1 +/+ males after phenobarbital treatment. Thus, KCNK1 suppresses phenobarbital-induced hyperplasia. These results indicate that phenobarbital treatment induces KCNK1 to elicit a male-specific and growth-suppressing signal. Thus, KCNK1 and Kcnk1 −/− mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice. PMID:23291559

Comparison of some characteristics of aerobic granules and sludge flocs from sequencing batch reactors.

PubMed

Li, J; Garny, K; Neu, T; He, M; Lindenblatt, C; Horn, H

2007-01-01

Physical, chemical and biological characteristics were investigated for aerobic granules and sludge flocs from three laboratory-scale sequencing batch reactors (SBRs). One reactor was operated as normal SBR (N-SBR) and two reactors were operated as granular SBRs (G-SBR1 and G-SBR2). G-SBR1 was inoculated with activated sludge and G-SBR2 with granules from the municipal wastewater plant in Garching (Germany). The following major parameters and functions were measured and compared between the three reactors: morphology, settling velocity, specific gravity (SG), sludge volume index (SVI), specific oxygen uptake rate (SOUR), distribution of the volume fraction of extracellular polymeric substances (EPS) and bacteria, organic carbon and nitrogen removal. Compared with sludge flocs, granular sludge had excellent settling properties, good solid-liquid separation, high biomass concentration, simultaneous nitrification and denitrification. Aerobic granular sludge does not have a higher microbial activity and there are some problems including higher effluent suspended solids, lower ratio of VSS/SS and no nitrification at the beginning of cultivation. Measurement with CLSM and additional image analysis showed that EPS glycoconjugates build one main fraction inside the granules. The aerobic granules from G-SBR1 prove to be heavier, smaller and have a higher microbial activity compared with G-SBR2. Furthermore, the granules were more compact, with lower SVI and less filamentous bacteria.

Transcriptional response of dermal fibroblasts in direct current electric fields.

PubMed

Jennings, Jessica; Chen, Dongquan; Feldman, Dale

2008-07-01

During the course of normal wound healing, fibroblasts at the wound edge are exposed to electric fields (EFs) ranging from 40 to 200 mV/mm. Various forms of EFs influence fibroblast migration, proliferation, and protein synthesis. Thus, EFs may contribute to fibroblast activation during wound repair. To elucidate the role of EFs during the normal progression of healing, this study compares gene expression in normal adult dermal fibroblasts exposed to a 100 mV/mm EF for 1 h to non-stimulated controls. Significantly increased expression of 162 transcripts and decreased expression of 302 transcripts was detected using microarrays, with 126 transcripts above the level of 1.4-fold increases or decreases compared to the controls. Above the level of twofold, only 11 genes were significantly increased or decreased compared to controls. Many of these significantly regulated genes are associated with wound repair through the processes of matrix production, cellular signaling, and growth. Activity within specific cellular signaling pathways is noted, including TGF-beta, G-proteins, and inhibition of apoptosis. In addition, RT-PCR analysis of the expression of KLF6, FN1, RGS2, and JMJD1C over continued stimulation and at different field strengths suggests that there are specific windows of field characteristics for maximum induction of these genes. EFs thus appear to have an important role in controlling fibroblast activity in the process of wound healing.

Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

PubMed

Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

2017-06-15

Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

Generating bifunctional fusion enzymes composed of heat-active endoglucanase (Cel5A) and endoxylanase (XylT).

PubMed

Rizk, Mazen; Elleuche, Skander; Antranikian, Garabed

2015-01-01

Bifunctional enzyme constructs were generated comprising two genes encoding heat-active endoglucanase (cel5A) and endoxylanase (xylT). The fused proteins Cel5A-XylT and XylT-Cel5A were active on both β-glucan and beechwood xylan. An improvement in endoglucanase and endoxylanase catalytic activities was observed. The specific activity of the fusion towards xylan was significantly raised when compared to XylT. The fusion constructs were active from 40 to 100 °C for endoglucanase and from 40 to 90 °C for endoxylanase, but the temperature optima were lowered from 90 to 80 °C for the endoglucanase and from 80 to 70 °C for the endoxylanase. XylT in the construct XylT-Cel5A was less stable at higher temperatures compared to Cel5A-XylT. Due to the enzymatic performance, these fusion enzymes are attractive candidates for applications in biorefineries based on plant waste.

Identification of Residues That Affect Oligomerization and/or Enzymatic Activity of Influenza Virus H5N1 Neuraminidase Proteins

PubMed Central

Dai, Meiling; Guo, Hongbo; Dortmans, Jos C. F. M.; Dekkers, Jojanneke; Nordholm, Johan; Daniels, Robert; van Kuppeveld, Frank J. M.; de Vries, Erik

2016-01-01

ABSTRACT Influenza A virus (IAV) attachment to and release from sialoside receptors is determined by the balance between hemagglutinin (HA) and neuraminidase (NA). The molecular determinants that mediate the specificity and activity of NA are still poorly understood. In this study, we aimed to design the optimal recombinant soluble NA protein to identify residues that affect NA enzymatic activity. To this end, recombinant soluble versions of four different NA proteins from H5N1 viruses were compared with their full-length counterparts. The soluble NA ectodomains were fused to three commonly used tetramerization domains. Our results indicate that the particular oligomerization domain used does not affect the Km value but may affect the specific enzymatic activity. This particularly holds true when the stalk domain is included and for NA ectodomains that display a low intrinsic ability to oligomerize. NA ectodomains extended with a Tetrabrachion domain, which forms a nearly parallel four-helix bundle, better mimicked the enzymatic properties of full-length proteins than when other coiled-coil tetramerization domains were used, which probably distort the stalk domain. Comparison of different NA proteins and mutagenic analysis of recombinant soluble versions thereof resulted in the identification of several residues that affected oligomerization of the NA head domain (position 95) and therefore the specific activity or sialic acid binding affinity (Km value; positions 252 and 347). This study demonstrates the potential of using recombinant soluble NA proteins to reveal determinants of NA assembly and enzymatic activity. IMPORTANCE The IAV HA and NA glycoproteins are important determinants of host tropism and pathogenicity. However, NA is relatively understudied compared to HA. Analysis of soluble versions of these glycoproteins is an attractive way to study their activities, as they are easily purified from cell culture media and applied in downstream assays. In the present study, we analyzed the enzymatic activity of different NA ectodomains with three commonly used tetramerization domains and compared them with full-length NA proteins. By performing a mutagenic analysis, we identified several residues that affected NA assembly, activity, and/or substrate binding. In addition, our results indicate that the design of the recombinant soluble NA protein, including the particular tetramerization domain, is an important determinant for maintaining the enzymatic properties within the head domain. NA ectodomains extended with a Tetrabrachion domain better mimicked the full-length proteins than when the other tetramerization domains were used. PMID:27512075

Proteomic identification of an embryo-specific 1Cys-Prx promoter and analysis of its activity in transgenic rice.

PubMed

Kim, Je Hein; Jung, In Jung; Kim, Dool Yi; Fanata, Wahyu Indra; Son, Bo Hwa; Yoo, Jae Yong; Harmoko, Rikno; Ko, Ki Seong; Moon, Jeong Chan; Jang, Ho Hee; Kim, Woe Yeon; Kim, Jae-Yean; Lim, Chae Oh; Lee, Sang Yeol; Lee, Kyun Oh

2011-04-29

Proteomic analysis of a rice callus led to the identification of 10 abscisic acid (ABA)-induced proteins as putative products of the embryo-specific promoter candidates. 5'-flanking sequence of 1 Cys-Prx, a highly-induced protein gene, was cloned and analyzed. The transcription initiation site of 1 Cys-Prx maps 96 nucleotides upstream of the translation initiation codon and a TATA-box and putative seed-specific cis-acting elements, RYE and ABRE, are located 26, 115 and 124 bp upstream of the transcription site, respectively. β-glucuronidase (GUS) expression driven by the 1 Cys-Prx promoters was strong in the embryo and aleurone layer and the activity reached up to 24.9 ± 3.3 and 40.5 ± 2.1 pmol (4 MU/min/μg protein) in transgenic rice seeds and calluses, respectively. The activity of the 1 Cys-Prx promoters is much higher than that of the previously-identified embryo-specific promoters, and comparable to that of strong endosperm-specific promoters in rice. GUS expression driven by the 1 Cys-Prx promoters has been increased by ABA treatment and rapidly induced by wounding in callus and at the leaf of the transgenic plants, respectively. Furthermore, ectopic expression of the GUS construct in Arabidopsis suggested that the 1 Cys-Prx promoter also has strong activity in seeds of dicot plants. Copyright © 2011 Elsevier Inc. All rights reserved.

Expression pattern of transcription factors and intracellular cytokines reveals that clinically cured tuberculosis is accompanied by an increase in Mycobacterium-specific Th1, Th2, and Th17 cells.

PubMed

da Silva, Marcos V; Massaro Junior, Vladimir J; Machado, Juliana R; Silva, Djalma A A; Castellano, Lúcio R; Alexandre, Patricia B D; Rodrigues, Denise B R; Rodrigues, Virmondes

2015-01-01

Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.

Muscarinic cholinergic receptor binding: in vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate

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

Drayer, B.; Jaszczak, R.; Coleman, E.

1982-06-01

An attempt was made to characterize, in vivo, specific binding to the muscarinic cholinergic receptor in the calf using the radioiodinated ligand quinuclidinyl benzilate (/sup 123/I-OH-QNB) and single photon detection emission computed tomography (SPECT). The supratentorial brain activity was significantly increased after the intravenous infusion of /sup 123/I-OH-QNB as compared to free /sup 123/I. Scopolamine, a muscarinic cholinergic receptor antagonist, decreased the measured brain activity when infused prior to /sup 123/I-OH-QNB consistent with pharmacologic blockade of specific receptor binding. Quantitative in vitro tissue distribution studies obtained following SPECT imaging were consistent with regionally distinct specific receptor binding in the striatummore » and cortical gray matter, nonspecific binding in the cerebellum, and pharmacologic blockade of specific binding sites with scopolamine. Although /sup 123/I-OH-QNB is not the ideal radioligand, our limited success will hopefully encourage the development of improved binding probes for SPECT imaging and quantitation.« less

Impact of T-cell-specific Smad4 deficiency on the development of autoimmune diabetes in NOD mice

PubMed Central

Kim, Donghee; Lee, Song Mi; Jun, Hee-Sook

2017-01-01

Type 1 diabetes results from autoimmune-mediated pancreatic beta-cell destruction and transforming growth factor-beta (TGF-β) is known to play a preventive role in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we investigated the role of Smad4, a key molecule for Smad-dependent TGF-β signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We generated T-cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the pathological and immunological changes. Smad4 tKO showed earlier onset and increased incidence of diabetes than wild type (WT) NOD mice. Pathological features such as insulitis, anti-glutamic acid decarboxylase auto-antibody levels and serum IFN-γ levels were significantly increased in Smad4 tKO compared with WT NOD mice. Proportion and number of activated/memory CD4+ T cell were significantly increased in pancreatic lymph nodes of Smad4 tKO compared with WT NOD mice. However, the proportion and function of regulatory T cells was not different. Effector CD4+ T cells from Smad4 tKO were more resistant to suppression by regulatory T cells than effector cells from WT NOD mice. The proliferative potential of effector T cells from Smad4 tKO was significantly elevated compared with WT NOD mice, and activation of sterol regulatory element binding protein-1c (SREBP-1c) in T cells of Smad4 tKO NOD mice was correlated with this proliferative activity. We conclude that Smad4 deletion in T cells of NOD mice accelerated the development of autoimmune diabetes and increased the incidence of the disease by dysregulation of T cell activation at least in part via SREBP-1c activation. PMID:27686408

Impact of T-cell-specific Smad4 deficiency on the development of autoimmune diabetes in NOD mice.

PubMed

Kim, Donghee; Lee, Song Mi; Jun, Hee-Sook

2017-03-01

Type 1 diabetes results from autoimmune-mediated pancreatic beta-cell destruction and transforming growth factor-beta (TGF-β) is known to play a preventive role in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we investigated the role of Smad4, a key molecule for Smad-dependent TGF-β signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We generated T-cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the pathological and immunological changes. Smad4 tKO showed earlier onset and increased incidence of diabetes than wild type (WT) NOD mice. Pathological features such as insulitis, anti-glutamic acid decarboxylase auto-antibody levels and serum IFN-γ levels were significantly increased in Smad4 tKO compared with WT NOD mice. Proportion and number of activated/memory CD4 + T cell were significantly increased in pancreatic lymph nodes of Smad4 tKO compared with WT NOD mice. However, the proportion and function of regulatory T cells was not different. Effector CD4 + T cells from Smad4 tKO were more resistant to suppression by regulatory T cells than effector cells from WT NOD mice. The proliferative potential of effector T cells from Smad4 tKO was significantly elevated compared with WT NOD mice, and activation of sterol regulatory element binding protein-1c (SREBP-1c) in T cells of Smad4 tKO NOD mice was correlated with this proliferative activity. We conclude that Smad4 deletion in T cells of NOD mice accelerated the development of autoimmune diabetes and increased the incidence of the disease by dysregulation of T cell activation at least in part via SREBP-1c activation.

Civilian-military coordination in the emergency response in Indonesia.

PubMed

Joyce, Neil

2006-10-01

Military and civilian humanitarian interventions in severely affected Indonesian province of Aceh are described following the tsunami of December 26. Specific events and activities illustrate the comparative roles of these types of agencies and how collaboration should recognize the abilities and limitations of each.

78 FR 12141 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... Bureau to monitor consumers' behavior--specifically, consumer use of deposit accounts as transactional... of Consumer Financial Protection (Bureau), and state supervisors of banks and savings associations... consumer customers compared to business customers, and [cir] For those institutions with $1 billion or more...

Recent Trends in Computerized Medical Information Systems for Hospital Departments

PubMed Central

Maturi, Vincent F.; DuBois, Richard M.

1980-01-01

The authors have re-examined the current state of commercially-available department-specific medical information systems and their relationship to the hospital-wide communications systems. The current state was compared to the state two years ago when the authors made their first survey. The changes in the trend, the number of problems that hospital administrators or department directors are faced with when purchasing or using department-specific systems, and the activity in standardization were studied.

The effect of feature-based attention on flanker interference processing: An fMRI-constrained source analysis.

PubMed

Siemann, Julia; Herrmann, Manfred; Galashan, Daniela

2018-01-25

The present study examined whether feature-based cueing affects early or late stages of flanker conflict processing using EEG and fMRI. Feature cues either directed participants' attention to the upcoming colour of the target or were neutral. Validity-specific modulations during interference processing were investigated using the N200 event-related potential (ERP) component and BOLD signal differences. Additionally, both data sets were integrated using an fMRI-constrained source analysis. Finally, the results were compared with a previous study in which spatial instead of feature-based cueing was applied to an otherwise identical flanker task. Feature-based and spatial attention recruited a common fronto-parietal network during conflict processing. Irrespective of attention type (feature-based; spatial), this network responded to focussed attention (valid cueing) as well as context updating (invalid cueing), hinting at domain-general mechanisms. However, spatially and non-spatially directed attention also demonstrated domain-specific activation patterns for conflict processing that were observable in distinct EEG and fMRI data patterns as well as in the respective source analyses. Conflict-specific activity in visual brain regions was comparable between both attention types. We assume that the distinction between spatially and non-spatially directed attention types primarily applies to temporal differences (domain-specific dynamics) between signals originating in the same brain regions (domain-general localization).

Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

PubMed Central

Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

2014-01-01

Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

Individual differences in cognitive reappraisal usage modulate the time course of brain activation during symptom provocation in specific phobia

PubMed Central

2013-01-01

Background Extinction learning is proposed to be one key mechanism of action underlying exposure-based cognitive-behavioral therapy (CBT) in specific phobia. Beyond that, cognitive reappraisal, one important strategy to regulate negative emotions, is a crucial component of CBT interventions, but has been disregarded in previous studies investigating neural change processes in specific phobia. The aim of this study was to investigate the association of individual differences in habitual/dispositional cognitive reappraisal usage and the time course of brain activation during phobic stimulation in specific phobia. Methods Dental phobic patients and healthy control subjects participated in a functional magnetic resonance imaging (fMRI) study whilst being confronted with phobic, disgust, fear and neutral pictures. Individual differences in cognitive reappraisal usage were assessed via a self-report questionnaire and correlated with activation decreases over the course of time. Results Phobic individuals with higher dispositional cognitive reappraisal scores showed a more pronounced activation decline in the right dorsomedial prefrontal cortex (dmPFC) which might be associated with a diminution of explicit cognitive emotion regulation over the course of time. Less decrease of activation in the right ventromedial prefrontal cortex (vmPFC) and the lateral orbitofrontal cortex (lOFC) over time in subjects with higher cognitive reappraisal scores might be related to a stronger automatic regulation of emotions or even emotional relearning. Additionally, phobic subjects compared with healthy controls showed a stronger habituation of the left dmPFC over the course of symptom provocation. Conclusions The results of this study show for the first time that individual differences in cognitive reappraisal usage are associated with the time course of brain activation during symptom provocation in specific phobia. Additionally, the present study gives first indications for the importance of considering individual differences in cognitive reappraisal usage in the treatment of specific phobia. PMID:23937792

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia

PubMed Central

Caminiti, Silvia P.; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F.

2015-01-01

Background bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. Objective To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). Methods We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Results Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Conclusions Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms. PMID:26594631

A systematic review of postoperative hand therapy management of basal joint arthritis.

PubMed

Wolfe, Terri; Chu, Jennifer Y; Woods, Tammy; Lubahn, John D

2014-04-01

There are a variety of postoperative immobilization and therapy options for patients with basal joint arthritis. Although prior systematic reviews have compared surgical procedures used to treat basal joint arthritis, none to our knowledge compares therapy protocols for this condition, which are considered an important part of the treatment. (1) We sought to determine whether differences in the length and type of postoperative immobilization affect clinical results after basal joint arthritis surgery. (2) We also compared specific therapy protocols that were prescribed. (3) Finally, we evaluated published protocols to determine when patients were released to full activity to see whether these appeared to affect clinical results. A systematic review of English-language studies in the PubMed and Cochrane databases was performed. Studies were then reviewed to determine what postoperative immobilization and therapy protocols the authors used and when patients were released to full activities. A total of 19 studies were identified using the search criteria. All but one of the studies included a postoperative period of immobilization in either a cast or splint. Immobilization time varied depending on whether Kirschner wires were used for the surgery and whether an implant was placed. Postoperative therapy protocols also varied but followed three general patterns. Some therapy protocols involved teaching patients a home exercise program only, whereas some authors described routine referral to a therapist. The third group consisted of studies in which patients were only referred for therapy if the physicians determined it was necessary during followup. Many studies did not give a specific time for full return to activity and instead described a gradual transition to full activity after immobilization was discontinued. Because of the variability and small numbers, no conclusive recommendations could be made on any of the three study questions. Comparative, multicenter studies comparing different immobilization and therapy protocols after the surgical treatment of basal joint arthritis would be helpful for both surgeons and therapists looking to refine their treatment protocols.

Fusion of an oligopeptide to the N terminus of an alkaline α-amylase from Alkalimonas amylolytica simultaneously improves the enzyme's catalytic efficiency, thermal stability, and resistance to oxidation.

PubMed

Yang, Haiquan; Lu, Xinyao; Liu, Long; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Chen, Jian

2013-05-01

In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes.

Fusion of an Oligopeptide to the N Terminus of an Alkaline α-Amylase from Alkalimonas amylolytica Simultaneously Improves the Enzyme's Catalytic Efficiency, Thermal Stability, and Resistance to Oxidation

PubMed Central

Yang, Haiquan; Lu, Xinyao; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R.; Du, Guocheng

2013-01-01

In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes. PMID:23455344

The Pot Calling the Kettle Black? A Comparison of Measures of Current Tobacco Use

PubMed Central

ROSENMAN, ROBERT

2014-01-01

Researchers often use the discrepancy between self-reported and biochemically assessed active smoking status to argue that self-reported smoking status is not reliable, ignoring the limitations of biochemically assessed measures and treating it as the gold standard in their comparisons. Here, we employ econometric techniques to compare the accuracy of self-reported and biochemically assessed current tobacco use, taking into account measurement errors with both methods. Our approach allows estimating and comparing the sensitivity and specificity of each measure without directly observing true smoking status. The results, robust to several alternative specifications, suggest that there is no clear reason to think that one measure dominates the other in accuracy. PMID:25587199

Law and Intergenerational Relationships.

PubMed

Doron, Israel; Lowenstein, Ariela; Biggs, Simon

2017-03-01

In any aging society, the sociolegal construction of intergenerational relationships is of great importance. This study conducts an international comparison of a specific judicial issue: whether active labor unions have the legal right to strike for the purpose of improving the benefits given to nonactive workers (specifically, pensioners). A comparative case law methodology was used. The texts of three different Supreme Court cases-in the United States, Canada, and Israel-were analyzed and compared. Despite the different legal outcomes, all three court rulings reflect a disregard of known and relevant social gerontology theories of intergenerational relationships. Social gerontological theories can play an important role in both understanding and shaping judicial policies and assisting the courts in choosing their sociojudicial narratives.

Biochemical Activities of Minute Virus of Mice Nonstructural Protein NS1 Are Modulated In Vitro by the Phosphorylation State of the Polypeptide

PubMed Central

Nüesch, Jürg P. F.; Corbau, Romuald; Tattersall, Peter; Rommelaere, Jean

1998-01-01

NS1, the 83-kDa major nonstructural protein of minute virus of mice (MVM), is a multifunctional nuclear phosphoprotein which is required in a variety of steps during progeny virus production, early as well as late during infection. NS1 is the initiator protein for viral DNA replication. It binds specifically to target DNA motifs; has site-specific single-strand nickase, intrinsic ATPase, and helicase activities; trans regulates viral and cellular promoters; and exerts cytotoxic stress on the host cell. To investigate whether these multiple activities of NS1 depend on posttranslational modifications, in particular phosphorylation, we expressed His-tagged NS1 in HeLa cells by using recombinant vaccinia viruses, dephosphorylated it at serine and threonine residues with calf intestine alkaline phosphatase, and compared the biochemical activities of the purified un(der)phosphorylated (NS1O) and the native (NS1P) polypeptides. Biochemical analyses of replicative functions of NS1O revealed a severe reduction of intrinsic helicase activity and, to a minor extent, of ATPase and nickase activities, whereas its affinity for the target DNA sequence [ACCA]2–3 was enhanced compared to that of NS1P. In the presence of endogenous protein kinases found in replication extracts, NS1O showed all functions necessary for resolution and replication of the 3′ dimer bridge, indicating reactivation of NS1O by rephosphorylation. Partial reactivation of the helicase activity was found as well when NS1O was incubated with protein kinase C. PMID:9733839

Electroencephalographic slow waves prior to sleepwalking episodes.

PubMed

Perrault, Rosemarie; Carrier, Julie; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

2014-12-01

Recent studies have suggested that the onset of sleepwalking episodes may be preceded by fluctuations in slow-wave sleep electroencephalographic characteristics. However, whether or not such fluctuations are specific to sleepwalking episodes or generalized to all sleep-wake transitions in sleepwalkers remains unknown. The goal of this study was to compare spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) as well as slow oscillation density before the onset of somnambulistic episodes versus non-behavioral awakenings recorded from the same group of sleepwalkers. A secondary aim was to describe the time course of observed changes in slow-wave activity and slow oscillations during the 3 min immediately preceding the occurrence of somnambulistic episodes. Twelve adult sleepwalkers were investigated polysomnographically during the course of one night. Slow-wave activity and slow oscillation density were significantly greater prior to patients' somnambulistic episodes as compared with non-behavioral awakenings. However, there was no evidence for a gradual increase over the 3 min preceding the episodes. Increased slow-wave activity and slow oscillation density appear to be specific to sleepwalking episodes rather than generalized to all sleep-wake transitions in sleepwalkers. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential changes in platelet VEGF, Tsp, CXCL12, and CXCL4 in patients with metastatic cancer.

PubMed

Wiesner, Tina; Bugl, Stefanie; Mayer, Frank; Hartmann, Jörg T; Kopp, Hans-Georg

2010-03-01

Data from animal studies indicate that platelets play a key role in tumor dissemination and metastasis. We therefore hypothesized that metastastic cancer patients may display a specific platelet phenotype. Percentage of activated, p-selectin positive platelets as well as platelet contents (i.e., plasma and platelet count-corrected serum levels of VEGF-A, CXCL12, CXCL4, and thrombospondin-1) were analyzed in 43 patients with newly diagnosed metastatic disease prior to treatment. Tumor patients had increased platelet counts and significantly elevated percentages of activated platelets. Moreover, the platelet content of VEGF-A in cancer patients was significantly increased compared to healthy controls, while thrombospondin-1, CXCL12 and CXCL4 were significantly decreased. Our data contain several unexpected results: firstly, CXCL12 was found in minute quantities in the serum as compared with murine studies. Secondly, CXCL4, which was found by mass spectrometry to be the single massively upregulated intraplatelet chemokine in mice after tumor xenotransplantation, was decreased in tumor patient platelets. While increased contents of VEGF-A have been attributed to platelet scavenger activity, the differential decrease of specific platelet contents may be due to differential secretion or altered megakaryopoiesis in metastatic cancer patients.

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

Activity profiles of the Australian female netball team players during international competition: implications for training practice.

PubMed

Fox, Aaron; Spittle, Michael; Otago, Leonie; Saunders, Natalie

2013-01-01

In elite sport, to remain competitive at the international level, it is critical to understand the game demands on players to ensure sport specific training programmes are designed for optimal athlete preparation and conditioning. In netball, recent research examining the activity patterns of players at the elite level is lacking, with only one study undertaken on this level of competition in the past 30 years. Therefore, the aim of this study was to provide coaches with up to date knowledge of player activity patterns as a basis for the design of optimal sport specific training programmes. The Australian female netball team were analysed using video footage of three international test matches. Player activity was categorised into five movement and eight game-based activities; and further classified as work or rest. Results suggest that differences in the current game exist when compared to the previous analysis. Positional differences were also found with regard to player activity confirming the need for an individualised component of training based on player position.

Analysis of methanogenic activity in a thermophilic-dry anaerobic reactor: use of fluorescent in situ hybridization.

PubMed

Montero, B; García-Morales, J L; Sales, D; Solera, R

2009-03-01

Methanogenic activity in a thermophilic-dry anaerobic reactor was determined by comparing the amount of methane generated for each of the organic loading rates with the size of the total and specific methanogenic population, as determined by fluorescent in situ hybridization. A high correlation was evident between the total methanogenic activity and retention time [-0.6988Ln(x)+2.667] (R(2) 0.8866). The total methanogenic activity increased from 0.04x10(-8) mLCH(4) cell(-1)day(-1) to 0.38x10(-8) mLCH(4) cell(-1)day(-1) while the retention time decreased, augmenting the organic loading rates. The specific methanogenic activities of H(2)-utilizing methanogens and acetate-utilizing methanogens increased until they stabilised at 0.64x10(-8) mLCH(4) cell(-1)day(-1) and 0.33x10(-8) mLCH(4) cell(-1)day(-1), respectively. The methanogenic activity of H(2)-utilizing methanogens was higher than acetate-utilizing methanogens, indicating that maintaining a low partial pressure of hydrogen does not inhibit the acetoclastic methanogenesis or the anaerobic process.

Synthesis and Photophysical Properties of Sulfonamidophenyl Porphyrins as Models for Activatable Photosensitizers

PubMed Central

Bhaumik, Jayeeta; Weissleder, Ralph; McCarthy, Jason R.

2009-01-01

The ability to localize agents to specific anatomic sites remains an important aspect in designing more efficient therapeutics. Light-activated therapies, in particular, allow for the focal ablation of target tissues and cells. In order to increase the specificity of these agents, stimuli-activated systems have been developed, which are non-phototoxic in the absence of activation. To this end, we propose a novel paradigm for excited state quenching and activation based upon the direct conjugation of quenching moieties to the porphyrinic macrocycle. Model compounds, based upon meso-(p-aminophenyl)porphyrins were synthesized bearing 1 to 4 sulfonamide-linked 2,4-dinitrobenzene. The singlet oxygen and fluorescence quantum yields of these compounds were obtained and compared, as well as the kinetics of activation with relevant activating agents. In addition, methods were developed to further modify the porphyrin in order to modulate the polarity and effect conjugation to biomolecules or nanoparticulate scaffolds. These systems may prove useful in the treatment of a number of disease states, such as cancer and bacterial infection. PMID:19610602

Direction-specific recruitment of rotator cuff muscles during bench press and row.

PubMed

Wattanaprakornkul, Duangjai; Halaki, Mark; Cathers, Ian; Ginn, Karen A

2011-12-01

Recent studies indicate that rotator cuff (RC) muscles are recruited in a reciprocal, direction-specific pattern during shoulder flexion and extension exercises. The main purpose of this study was to determine if similar reciprocal RC recruitment occurs during bench press (flexion-like) and row (extension-like) exercises. In addition, shoulder muscle activity was comprehensively compared between bench press and flexion; row and extension; and bench press and row exercises. Electromyographic (EMG) activity was recorded from 9 shoulder muscles sites in 15 normal volunteers. All exercises were performed at 20, 50 and 70% of subjects' maximal load. EMG data were normalized to standard maximal voluntary contractions. Infraspinatus activity was significantly higher than subscapularis during bench press, with the converse pattern during the row exercise. Significant differences in activity levels were found in pectoralis major, deltoid and trapezius between the bench press and flexion exercises and in lower trapezius between the row and extension exercises. During bench press and row exercises, the recruitment pattern in each active muscle did not vary with load. During bench press and row exercises, RC muscles contract in a reciprocal direction-specific manner in their role as shoulder joint dynamic stabilizers to counterbalance antero-posterior translation forces. Copyright © 2011 Elsevier Ltd. All rights reserved.

Contextually Mediated Spontaneous Retrieval Is Specific to the Hippocampus

PubMed Central

Long, Nicole M.; Sperling, Michael R.; Worrell, Gregory A.; Davis, Kathryn A.; Gross, Robert E.; Lega, Bradley C.; Jobst, Barbara C.; Sheth, Sameer A.; Zaghloul, Kareem; Stein, Joel M.; Kahana, Michael J.

2018-01-01

SUMMARY Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task. To identify neural activity specifically associated with contextual retrieval, we compared correct recalls, intrusions (incorrect recall of either items from prior lists or items not previously studied), and deliberations (matched periods during recall when no items came to mind). Neural signals that differentiate correct recalls from both other retrieval classes reflect contextual retrieval, as correct recalls alone arise from the correct context. We found that in the hippocampus, high-frequency activity (HFA, 44–100 Hz), a proxy for neural activation [4], was greater prior to correct recalls relative to the other retrieval classes, with no differentiation between intrusions and deliberations. This pattern was not observed in other memory-related cortical regions, including DLPFC, thus supporting a specific hippocampal contribution to contextually mediated memory retrieval. PMID:28343962

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.

Functional MRI study of specific animal phobia using an event-related emotional counting stroop paradigm.

PubMed

Britton, Jennifer C; Gold, Andrea L; Deckersbach, Thilo; Rauch, Scott L

2009-01-01

Emotional interference tasks may be useful in probing anterior cingulate cortex (ACC) function to understand abnormal attentional study in individuals with specific phobia. In a 3 T functional MRI study, individuals with specific phobias of the animal subtype (SAP, n=12) and healthy comparison (HC) adults (n=12) completed an event-related emotional counting Stroop task. Individuals were presented phobia-related, negative, and neutral words and were instructed to report via button press the number of words displayed on each trial. Compared to the HC group, the SAP group exhibited greater rostral ACC activation (i.e., greater response to phobia-related words than neutral words). In this same contrast, HCs exhibited greater right amygdala and posterior insula activations as well as greater thalamic deactivation than the SAP group. Both groups exhibited anterior cingulate, dorsomedial prefrontal cortex, inferior frontal gyrus/insula, and amygdala activations as well as thalamic deactivation. Psychophysiological interaction analysis highlighted a network of activation in these regions in response to phobia-related words in the SAP group. Taken together, these findings implicate a circuit of dysfunction, which is linked to attention abnormalities in individuals with SAP.

Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses.

PubMed

Gao, Yunfei; Zhang, Dongqing; Sun, Buxiang; Fujii, Hajime; Kosuna, Ken-Ichi; Yin, Zhinan

2006-10-01

Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL/6 mice were orally administered AHCC or water, followed by tumor cell inoculation. We showed that compared to pure water-treated mice, AHCC treatment significantly delayed tumor development after inoculation of either melanoma cell line B16F0 or lymphoma cell line EL4. Treatment with AHCC enhanced both Ag-specific activation and proliferation of CD4(+) and CD8(+) T cells, increased the number of tumor Ag-specific CD8(+) T cells, and more importantly, increased the frequency of tumor Ag-specific IFN-gamma producing CD8(+) T cells. Interestingly, AHCC treatment also showed increased cell number of NK and gammadelta T cells, indicating the role of AHCC in activating these innate-like lymphocytes. In summary, our results demonstrate that AHCC can enhance tumor immune surveillance through regulating both innate and adaptive immune responses.

The measurement of radiation exposure of astronauts by radiochemical techniques

NASA Technical Reports Server (NTRS)

Brodzinski, R. L.

1972-01-01

Cosmic radiation doses to the crews of the Apollo 14, 15, and 16 missions of 142 + or - 80, 340 + or - 80, and 210 + or - 130 mR respectively were calculated from the specific activities of Na-22 and Na-24 in the postflight urine specimens of the astronauts. The specific activity of Fe-59 was higher in the urine than in the feces of the Apollo 14 and 15 astronauts, and a possible explanation is given. The concentrations of K-40, K-42, Cr-51, Co-60, and Cs-137 in the urine are also reported for these astronauts. The radiation doses received by pilots and navigators flying high altitude missions during the solar flare of March 27 to 30, 1972 were calculated from the specific activity of Na-24 in their urine. These values are compared with the expected radiation dose calculated from the known shape and intensity of the proton spectrum and demonstrate the magnitude of atmospheric shielding. The concentrations of Na, K, Rb, Cs, Fe, Co, Ag, Zn, Hg, As, Sb, Se, and Br were measured in the urine specimens from the Apollo 14 and 15 astronauts by neutron activation analysis. The mercury and arsenic levels were much higher than expected.

A variational Bayes spatiotemporal model for electromagnetic brain mapping.

PubMed

Nathoo, F S; Babul, A; Moiseev, A; Virji-Babul, N; Beg, M F

2014-03-01

In this article, we present a new variational Bayes approach for solving the neuroelectromagnetic inverse problem arising in studies involving electroencephalography (EEG) and magnetoencephalography (MEG). This high-dimensional spatiotemporal estimation problem involves the recovery of time-varying neural activity at a large number of locations within the brain, from electromagnetic signals recorded at a relatively small number of external locations on or near the scalp. Framing this problem within the context of spatial variable selection for an underdetermined functional linear model, we propose a spatial mixture formulation where the profile of electrical activity within the brain is represented through location-specific spike-and-slab priors based on a spatial logistic specification. The prior specification accommodates spatial clustering in brain activation, while also allowing for the inclusion of auxiliary information derived from alternative imaging modalities, such as functional magnetic resonance imaging (fMRI). We develop a variational Bayes approach for computing estimates of neural source activity, and incorporate a nonparametric bootstrap for interval estimation. The proposed methodology is compared with several alternative approaches through simulation studies, and is applied to the analysis of a multimodal neuroimaging study examining the neural response to face perception using EEG, MEG, and fMRI. © 2013, The International Biometric Society.

Putative storage root specific promoters from cassava and yam: cloning and evaluation in transgenic carrots as a model system.

PubMed

Arango, Jacobo; Salazar, Bertha; Welsch, Ralf; Sarmiento, Felipe; Beyer, Peter; Al-Babili, Salim

2010-06-01

A prerequisite for biotechnological improvements of storage roots is the availability of tissue-specific promoters enabling high expression of transgenes. In this work, we cloned two genomic fragments, pMe1 and pDJ3S, controlling the expression of a gene with unknown function from cassava (Manihot esculenta) and of the storage protein dioscorin 3 small subunit gene from yam (Dioscorea japonica), respectively. Using beta-glucuronidase as a reporter, the activities of pMe1 and pDJ3S were evaluated in independent transgenic carrot lines and compared to the constitutive CaMV35S and the previously described cassava p15 promoters. Activities of pMe1 and pDJ3S in storage roots were assessed using quantitative GUS assays that showed pDJ3S as the most active one. To determine organ specificities, uidA transcript levels in leaves, stems and roots were measured by real-time RT-PCR analyses showing highest storage root specificity for pDJ3S. Root cross sections revealed that pMe1 was highly active in secondary xylem. In contrast, pDJ3S was active in all root tissues except for the central xylem. The expression patterns caused by the cassava p15 promoter in carrot storage roots were consistent with its previously described activities for the original storage organ. Our data demonstrate that the pDJ3S and, to a lesser extent, the pMe1 regulatory sequences represent feasible candidates to drive high and preferential expression of genes in carrot storage roots.

A smart drug: a pH-responsive photothermal ablation agent for Golgi apparatus activated cancer therapy.

PubMed

Xue, Fengfeng; Wen, Ying; Wei, Peng; Gao, Yilin; Zhou, Zhiguo; Xiao, Shuzhang; Yi, Tao

2017-06-13

We report a pH-responsive photothermal ablation agent (pH-PTT) based on cyanine dyes for photothermal therapy (PTT). The nanoparticles formed by BSA and pH-PTT preferentially accumulated in the Golgi apparatus of cancer cells compared to normal cells, and thus can be specifically activated by the acidic Golgi apparatus in cancer cells for effective PTT both ex vivo and in vivo.

Aryl diazonium for biomolecules immobilization onto SPRi chips.

PubMed

Mandon, Céline A; Blum, Loïc J; Marquette, Christophe A

2009-12-21

A method for the immobilization of proteins at the surface of surface plasmon resonance imaging (SPRi) chips is presented. The technology, based on the electro-deposition of a 4-carboxymethyl aryl diazonium (CMA) monolayer is compared to a classical thioctic acid self-assembled monolayer. SPRi live recording experiments followed by the quantification of the diazonium surface coverage demonstrate the presence of a monolayer of electro-deposited molecules (11*10(12) molecules mm(-2)). This monolayer, when activated through a classical carbodiimide route, generates a surface suitable for the protein immobilization. In the present study, protein A and BSA are immobilized as specific and control spots (150 microm id), respectively. The AFM characterization of the spots deposited onto CMA or thioctic acid modified chips prove the presence of 4.7 nm protein monolayers. Finally, the SPRi detection capabilities of the two surface chemistries are compared according to specific signal, non-specific interaction and regeneration possibilities. Advantages are given to the CMA surface modification since no measurable non-specific signal is obtained while reaching a higher specific signal.

Activation Loop Dynamics Determine the Different Catalytic Efficiencies of B Cell- and T Cell-Specific Tec Kinases

PubMed Central

Joseph, Raji E.; Kleino, Iivari; Wales, Thomas E.; Xie, Qian; Fulton, D. Bruce; Engen, John R.; Berg, Leslie J.; Andreotti, Amy H.

2014-01-01

Itk and Btk are nonreceptor tyrosine kinases of the Tec family that signal downstream of the T cell receptor (TCR) and B cell receptor (BCR), respectively. Despite their high sequence similarity and related signaling roles, Btk is a substantially more active kinase than Itk. We showed that substitution of six of the 619 amino acid residues of Itk with those of Btk was sufficient to completely switch the activities of Itk and Btk. The substitutions responsible for the swap in activity are all localized to the activation segment of the kinase domain. Nuclear magnetic resonance and hydrogen-deuterium exchange mass spectrometry analyses revealed that Itk and Btk had distinct protein dynamics in this region, which could explain the observed differences in catalytic efficiency between these kinases. Introducing Itk with enhanced activity into T cells led to enhanced and prolonged TCR signaling compared to that in cells with wild-type Itk. These findings imply that evolutionary pressures have led to Tec kinases having distinct enzymatic properties depending on the cellular context. We suggest that the weaker catalytic activities observed for T cell–specific kinases is one mechanism to regulate cellular activation and prevent aberrant immune responses. PMID:23982207

Proteolytic activities of kiwifruit actinidin (Actinidia deliciosa cv. Hayward) on different fibrous and globular proteins: a comparative study of actinidin with papain.

PubMed

Chalabi, Maryam; Khademi, Fatemeh; Yarani, Reza; Mostafaie, Ali

2014-04-01

Actinidin, a member of the papain-like family of cysteine proteases, is abundant in kiwifruit. To date, a few studies have been provided to investigate the proteolytic activity and substrate specificity of actinidin on native proteins. Herein, the proteolytic activity of actinidin was compared to papain on several different fibrous and globular proteins under neutral, acidic and basic conditions. The digested samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometry to assess the proteolytic effect. Furthermore, the levels of free amino nitrogen (FAN) of the treated samples were determined using the ninhydrin colorimetric method. The findings showed that actinidin has no or limited proteolytic effect on globular proteins such as immunoglobulins including sheep IgG, rabbit IgG, chicken IgY and fish IgM, bovine serum albumin (BSA), lipid transfer protein (LTP), and whey proteins (α-lactalbumin and β-lactoglobulin) compared to papain. In contrast to globular proteins, actinidin could hydrolyze collagen and fibrinogen perfectly at neutral and mild basic pHs. Moreover, this enzyme could digest pure α-casein and major subunits of micellar casein especially in acidic pHs. Taken together, the data indicated that actinidin has narrow substrate specificity with the highest enzymatic activity for the collagen and fibrinogen substrates. The results describe the actinidin as a mild plant protease useful for many special applications such as cell isolation from different tissues and some food industries as a mixture formula with other relevant proteases.

Comparative Studies of Enzymes Related to Serine Metabolism in Higher Plants 1

PubMed Central

Cheung, Geoffrey P.; Rosenblum, I. Y.; Sallach, H. J.

1968-01-01

The following enzymes related to serine metabolism in higher plants have been investigated: 1) d-3-phosphoglycerate dehydrogenase, 2) phosphohydroxypyruvate:l-glutamate transaminase, 3) d-glycerate dehydrogenase, and 4) hydroxypyruvate:l-alanine transaminase. Comparative studies on the distribution of the 2 dehydrogenases in seeds and leaves from various plants revealed that d-3-phosphoglycerate dehydrogenase is widely distributed in seeds in contrast to d-glycerate dehydrogenase, which is either absent or present at low levels, and that the reverse pattern is observed in green leaves. The levels of activity of the 4 enzymes listed above were followed in different tissues of the developing pea (Pisum sativum, var. Alaska). In the leaf, from the tenth to seventeenth day of germination, the specific activity of d-glycerate dehydrogenase increased markedly and was much higher than d-3-phosphoglycerate dehydrogenase which remained relatively constant during this time period. Etiolation resulted in a decrease in d-glycerate dehydrogenase and an increase in d-3-phosphoglycerate dehydrogenase activities. In apical meristem, on the other hand, the level of d-3-phosphoglycerate dehydrogenase exceeded that of d-glycerate dehydrogenase at all time periods studied. Low and decreasing levels of both dehydrogenases were found in epicotyl and cotyledon. The specific activities of the 2 transaminases remained relatively constant during development in both leaf and apical meristem. In general, however, the levels of phosphohydroxypyruvate:l-glutamate transaminase were comparable to those of d-3-phosphoglycerate dehydrogenase in a given tissue as were those for hydroxypyruvate: l-alanine transaminase and d-glycerate dehydrogenase. PMID:5699148

Meet the multifunctional and sexy glycoforms of glycodelin.

PubMed

Lapid, Kfir; Sharon, Nathan

2006-03-01

Glycodelin, a human-secreted glycoprotein that appears in a small number of glycoforms, exhibits diverse biological activities, such as in contraception and immunosuppression. Moreover, different tissue-specific glycoforms appear to mediate diverse functions. Quite unusually, the glycodelin N-linked glycans differ between the male and female glycoforms. The fact that these glycans are fundamental for exerting the physiological activities of the different glycoforms, makes them an interesting target for glycobiology research. This review will focus on the involvement of the glycans in glycodelin activity and compare between the several glycoforms.

Influences of internal resistance and specific surface area of electrode materials on characteristics of electric double layer capacitors

NASA Astrophysics Data System (ADS)

Suda, Yoshiyuki; Mizutani, Akitaka; Harigai, Toru; Takikawa, Hirofumi; Ue, Hitoshi; Umeda, Yoshito

2017-01-01

We fabricated electric double layer capacitors (EDLCs) using particulate and fibrous types of carbon nanomaterials with a wide range of specific surface areas and resistivity as an active material. The carbon nanomaterials used in this study are carbon nanoballoons (CNBs), onion-like carbon (OLC), and carbon nanocoils (CNCs). A commercially used activated carbon (AC) combined with a conductive agent was used as a comparison. We compared the EDLC performance using cyclic voltammetry (CV), galvanostatic charge/discharge testing, and electrochemical impedance spectroscopy (EIS). OLC showed a poor EDLC performance, although it has the lowest resistivity among the carbon nanomaterials. CNB, which has a 1/16 lower specific surface area than AC but higher specific surface area than CNC and OLC, had a higher specific capacitance than CNC and OLC. Moreover, at current densities of 1.5 Ag-1 and larger, the specific capacitance of the EDLC using CNB was almost the same as that using AC. Electrochemical impedance spectroscopy of the EDLCs revealed that the CNB and CNC electrodes had a much lower internal resistance than the AC electrode, which correlated with a low capacitance maintenance factor as the current density increased.

Cross-Cultural Differences in the Neural Correlates of Specific and General Recognition

PubMed Central

Paige, Laura E.; Ksander, John C.; Johndro, Hunter A.; Gutchess, Angela H.

2017-01-01

Research suggests that culture influences how people perceive the world, which extends to memory specificity, or how much perceptual detail is remembered. The present study investigated cross-cultural differences (Americans vs. East Asians) at the time of encoding in the neural correlates of specific vs. general memory formation. Participants encoded photos of everyday items in the scanner and 48 hours later completed a surprise recognition test. The recognition test consisted of same (i.e., previously seen in scanner), similar (i.e., same name, different features), or new photos (i.e., items not previously seen in scanner). For Americans compared to East Asians, we predicted greater activation in the hippocampus and right fusiform for specific memory at recognition, as these regions were implicated previously in encoding perceptual details. Results revealed that East Asians activated the left fusiform and left hippocampus more than Americans for specific vs. general memory. Follow-up analyses ruled out alternative explanations of retrieval difficulty and familiarity for this pattern of cross-cultural differences at encoding. Results overall suggest that culture should be considered as another individual difference that affects memory specificity and modulates neural regions underlying these processes. PMID:28256199

Cross-cultural differences in the neural correlates of specific and general recognition.

PubMed

Paige, Laura E; Ksander, John C; Johndro, Hunter A; Gutchess, Angela H

2017-06-01

Research suggests that culture influences how people perceive the world, which extends to memory specificity, or how much perceptual detail is remembered. The present study investigated cross-cultural differences (Americans vs East Asians) at the time of encoding in the neural correlates of specific versus general memory formation. Participants encoded photos of everyday items in the scanner and 48 h later completed a surprise recognition test. The recognition test consisted of same (i.e., previously seen in scanner), similar (i.e., same name, different features), or new photos (i.e., items not previously seen in scanner). For Americans compared to East Asians, we predicted greater activation in the hippocampus and right fusiform for specific memory at recognition, as these regions were implicated previously in encoding perceptual details. Results revealed that East Asians activated the left fusiform and left hippocampus more than Americans for specific versus general memory. Follow-up analyses ruled out alternative explanations of retrieval difficulty and familiarity for this pattern of cross-cultural differences at encoding. Results overall suggest that culture should be considered as another individual difference that affects memory specificity and modulates neural regions underlying these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Place specificity of monopolar and tripolar stimuli in cochlear implants: the influence of residual masking.

PubMed

Fielden, Claire A; Kluk, Karolina; McKay, Colette M

2013-06-01

This experiment investigated whether place specificity of neural activity evoked by cochlear implant stimulation is improved in tripolar compared to monopolar mode using a forward masking protocol addressing some limitations of previous methods of measurement and analysis. The amount of residual masking (masking remaining at long masker-probe delays) was also measured, and its potential influence on the specificity measures was evaluated. The masker stimulus comprised equally loud interleaved mono- or tripolar stimulation on two electrodes equidistant from a central probe electrode in an apical and basal direction, reducing the influence of off-site listening. The effect of masker-probe distance on the threshold shift of the tripolar probe was analyzed to derive a measure of place specificity. On average, tripolar maskers were more place specific than monopolar maskers, although the mean effect was small. There was no significant effect of masker level on specificity or on the differences observed between modes. The mean influence of residual masking on normalized masking functions was similar for the two modes and, therefore, did not influence the comparison of specificity between the modes. However, variability in amount of residual masking was observed between subjects, and therefore should be considered in forward masking studies that compare place specificity across subjects.

Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain

PubMed Central

Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo

2010-01-01

Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL-1β, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699

Sex differences in the neural bases of social appraisals.

PubMed

Veroude, Kim; Jolles, Jelle; Croiset, Gerda; Krabbendam, Lydia

2014-04-01

Behavioral research has demonstrated an advantage for females compared with males in social information processing. However, little is known about sex-related differences in brain activation during understanding of self and others. In the current functional magnetic resonance imaging study, this was assessed in late adolescents (aged 18-19) and young adults (aged 23-25) when making appraisals of self and other as well as reflected self-appraisals. Across all groups and for all appraisal conditions, activation was observed in the medial prefrontal cortex, medial posterior parietal cortex, left and right dorsolateral prefrontal cortex and left posterior parietal cortex. Males activated the medial posterior parietal cortex and bilateral temporoparietal junction more than females. The precuneus showed stronger activation in males compared with females specifically during appraisals of others. No differences between late adolescents and young adults were found. These results indicate that sex differences exist in the neural bases of social understanding.

Semi-synthesis of dihydrochalcone derivatives and their in vitro antimicrobial activities.

PubMed

Awouafack, Maurice D; Kusari, Souvik; Lamshöft, Marc; Ngamga, Dieudonne; Tane, Pierre; Spiteller, Michael

2010-04-01

We describe the semi-synthesis of dihydrochalcone derivatives and their IN VITRO antimicrobial activities. These compounds were prepared by modifying two naturally occurring antimicrobial dihydrochalcones, erioschalcones A and B, reported by us earlier. The structures of the compounds were assigned on the basis of spectroscopic evidence and by comparing their physical and spectroscopic data with those reported in the literature. All the compounds were subjected to IN VITRO antimicrobial assays against a panel of pathogenic microorganisms, including gram-positive and gram-negative bacteria, and fungi. The antimicrobial efficacies of this class of compounds were established by correlating the activity profile of each compound with its structure and by comparing the activities of all the compounds with each other based on their structure. This should enable the development of other derivatives of the dihydrochalcone family that would serve as more potent antimicrobial agents against specific pathogens. Georg Thieme Verlag KG Stuttgart.New York.

Fiber type-specific analysis of AMPK isoforms in human skeletal muscle: advancement in methods via capillary nanoimmunoassay.

PubMed

Tobias, Irene S; Lazauskas, Kara K; Arevalo, Jose A; Bagley, James R; Brown, Lee E; Galpin, Andrew J

2018-04-01

Human skeletal muscle is a heterogeneous mixture of multiple fiber types (FT). Unfortunately, present methods for FT-specific study are constrained by limits of protein detection in single-fiber samples. These limitations beget compensatory resource-intensive procedures, ultimately dissuading investigators from pursuing FT-specific research. Additionally, previous studies neglected hybrid FT, confining their analyses to only pure FT. Here we present novel methods of protein detection across a wider spectrum of human skeletal muscle FT using fully automated capillary nanoimmunoassay (CNIA) technology. CNIA allowed a ~20-fold-lower limit of 5'-AMP-activated protein kinase (AMPK) detection compared with Western blotting. We then performed FT-specific assessment of AMPK expression as a proof of concept. Individual human muscle fibers were mechanically isolated, dissolved, and myosin heavy chain (MHC) fiber typed via SDS-PAGE. Single-fiber samples were combined in pairs and grouped into MHC I, MHC I/IIa, MHC IIa, and MHC IIa/IIx for expression analysis of AMPK isoforms α 1 , α 2 , β 1 , β 2 , γ 2 , and γ 3 with a tubulin loading control. Significant FT-specific differences were found for α 2 (1.7-fold higher in MHC IIa and MHC IIa/IIx vs. others), γ 2 (2.5-fold higher in MHC IIa vs. others), and γ 3 (2-fold higher in MHC IIa and 4-fold higher in MHC IIa/IIx vs. others). Development of a protocol that combines the efficient and sensitive CNIA technology with comprehensive SDS-PAGE fiber typing marks an important advancement in FT-specific research because it allows more precise study of the molecular mechanisms governing metabolism, adaptation, and regulation in human muscle. NEW & NOTEWORTHY We demonstrate the viability of applying capillary nanoimmunoassay technology to the study of fiber type-specific protein analysis in human muscle fibers. This novel technique enables a ~20-fold-lower limit of protein detection compared with traditional Western blotting methods. Combined with SDS-PAGE methods of fiber typing, we apply this technique to compare 5'-AMP-activated protein kinase isoform expression in myosin heavy chain (MHC) I, MHC I/IIa, MHC IIa, and MHC IIa/IIx fiber types.

Don't worry, be happy: cross-sectional associations between physical activity and happiness in 15 European countries.

PubMed

Richards, Justin; Jiang, Xiaoxiao; Kelly, Paul; Chau, Josephine; Bauman, Adrian; Ding, Ding

2015-01-31

Mental health disorders are major contributors to the global burden of disease and their inverse relationship with physical activity is widely accepted. However, research on the association between physical activity and positive mental health outcomes is limited. Happiness is an example of a positive construct of mental health that may be promoted by physical activity and could increase resilience to emotional perturbations. The aim of this study is to use a large multi-country dataset to assess the association of happiness with physical activity volume and its specificity to intensity and/or activity domain. We analysed Eurobarometer 2002 data from 15 countries (n = 11,637). This comprised one question assessing self-reported happiness on a six point scale (dichotomised: happy/unhappy) and physical activity data collected using the IPAQ-short (i.e. walking, moderate, vigorous) and four domain specific items (i.e. domestic, leisure, transport, vocation). Logistic regression was used to examine the association between happiness and physical activity volume adjusted for sex, age, country, general health, relationship status, employment and education. Analyses of intensity and domain specificity were assessed by logistic regression adjusted for the same covariates and physical activity volume. When compared to inactive people, there was a positive dose-response association between physical activity volume and happiness (highly active: OR = 1.52 [1.28-1.80]; sufficiently active: OR = 1.29 [1.11-1.49]; insufficiently active: OR = 1.20 [1.03-1.39]). There were small positive associations with happiness for walking (OR = 1.02 [1.00-1.03]) and vigorous-intensity physical activity (OR = 1.03 [1.01-1.05). Moderate-intensity physical activity was not associated with happiness (OR = 1.01 [0.99-1.03]). The strongest domain specific associations with happiness were found for "a lot" of domestic (OR = 1.42 [1.20-1.68]) and "some" vocational (OR = 1.33 [1.08-1.64]) physical activity. Happiness was also associated with "a lot" of leisure physical activity (OR = 1.15 [1.02-1.30]), but there were no significant associations for the transport domain. Increasing physical activity volume was associated with higher levels of happiness. Although the influence of physical activity intensity appeared minimal, the association with happiness was domain specific and was strongest for "a lot" of domestic and/or "some" vocational physical activity. Future studies to establish causation are indicated and may prompt changes in how physical activity for improving mental health is promoted.

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.

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Respiration and enzymatic activities as indicators of stabilization of sewage sludge composting.

PubMed

Nikaeen, Mahnaz; Nafez, Amir Hossein; Bina, Bijan; Nabavi, BiBi Fatemeh; Hassanzadeh, Akbar

2015-05-01

The objective of this work was to study the evolution of physico-chemical and microbial parameters in the composting process of sewage sludge (SS) with pruning wastes (PW) in order to compare these parameters with respect to their applicability in the evaluation of organic matter (OM) stabilization. To evaluate the composting process and organic matter stability, different microbial activities were compared during composting of anaerobically digested SS with two volumetric ratios, 1:1 and 3:1 of PW:SS and two aeration techniques including aerated static piles (ASP) and turned windrows (TW). Dehydrogenase activity, fluorescein diacetate hydrolysis, and specific oxygen uptake rate (SOUR) were used as microbial activity indices. These indices were compared with traditional parameters, including temperature, pH, moisture content, organic matter, and C/N ratio. The results showed that the TW method and 3:1 (PW:SS) proportion was superior to the ASP method and 1:1 proportion, since the former accelerate the composting process by catalyzing the OM stabilization. Enzymatic activities and SOUR, which reflect microbial activity, correlated well with temperature fluctuations. Based on these results it appears that SOUR and the enzymatic activities are useful parameters to monitor the stabilization of SS compost. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive-Behavioral Treatment versus an Active Control for Children and Adolescents with Anxiety Disorders: A Randomized Trial

ERIC Educational Resources Information Center

Hudson, Jennifer L.; Rapee, Ronald M.; Deveney, Charise; Schniering, Carolyn A.; Lyneham, Heidi J.; Bavopoulos, Nataly

2009-01-01

Specific delivery of cognitive-behavioral skills is more effective in treating childhood anxiety compared to treatment that contains only nonspecific therapy factors. The findings are based on a randomized trial involving 112 children aged 7-16 years.

Web-Assisted Vocational Test Interpretation.

ERIC Educational Resources Information Center

Jones, W. Paul; Harbach, Robert L.; Coker, J. Kelly; Staples, Pamela A.

2002-01-01

Compares the effectiveness of a specific employment counseling activity, vocational interest inventory interpretation, across 3 delivery modalities: online text chat; online text chat with video cues; and traditional face-to-face interpretation. The difference in ratings of session value between text chat and video and face-to-face modalities was…

Information Politics, Transnational Advocacy, and Education for All

ERIC Educational Resources Information Center

Magrath, Bronwen

2015-01-01

This article explores transnational activism within Education for All (EFA), looking specifically at the strategic use of information and research by transnational advocacy organizations. Through a comparative case-study examination of two prominent civil society organizations within the EFA movement--the Asia South Pacific Association for Basic…

Comparative genomics reveals tissue-specific regulation of prolactin receptor gene expression

USDA-ARS?s Scientific Manuscript database

Prolactin (PRL), acting via the prolactin receptor, fulfills a diversity of biological functions including the maintenance of solute balance and mineral homeostasis via tissues such as the heart, kidneys and intestine. Expression and activity of the prolactin receptor (PRLR) is regulated by various ...

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.

Laminar circuit organization and response modulation in mouse visual cortex

PubMed Central

Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

2012-01-01

The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

Autophagy activation, not peroxisome proliferator-activated receptor γ coactivator 1α, may mediate exercise-induced improvements in glucose handling during diet-induced obesity.

PubMed

Rosa-Caldwell, Megan E; Brown, Jacob L; Lee, David E; Blackwell, Thomas A; Turner, Kyle W; Brown, Lemuel A; Perry, Richard A; Haynie, Wesley S; Washington, Tyrone A; Greene, Nicholas P

2017-09-01

What is the central question of this study? What are the individual and combined effects of muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) overexpression and physical activity during high-fat feeding on glucose and exercise tolerance? What is the main finding and its importance? Our main finding is that muscle-specific PGC-1α overexpression provides no protection against lipid-overload pathologies nor does it enhance exercise adaptations. Instead, physical activity, regardless of PGC-1α content, protects against high-fat diet-induced detriments. Activation of muscle autophagy was correlated with exercise protection, suggesting that autophagy might be a mediating factor for exercise-induced protection from lipid overload. The prevalence of glucose intolerance is alarmingly high. Efforts to promote mitochondrial biogenesis through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) to mitigate glucose intolerance have been controversial. However, physical activity remains a primary means to alleviate the condition. The aim of this study was to determine the combined effects of muscle-specific overexpression of PGC-1α and physical activity on glucose handling during diet-induced obesity. Wild-type (WT, ∼20) and PGC-1α muscle transgenic (MCK-PGC-1α, ∼20) mice were given a Western diet (WD) at 8 weeks age and allowed to consume food ab libitum throughout the study. At 12 weeks of age, all animals were divided into sedentary (SED) or voluntary wheel running (VWR) interventions. At 7, 11 and 15 weeks of age, animals underwent glucose tolerance tests (GTT) and graded exercise tests (GXT). At 16 weeks of age, tissues were collected. At 11 weeks, the MCK-PGC-1α animals had 50% greater glucose tolerance integrated area under the curve compared with WT. However, at 15 weeks, SED animals also had greater GTT integrated area under the curve compared with VWR, regardless of genotype; furthermore, SED animals demonstrated reduced exercise capacity compared with earlier time points, which was not seen in VWR animals. Voluntary distance run per day was correlated with GTT in VWR-WT, but not VWR-MCK-PGC-1α mice. Voluntary wheel running and genotype independently resulted in a greater LC3II/LC3I ratio, suggesting enhanced autophagosome formation, which was correlated with exercise-induced improvements in GTT. In conclusion, artificially increasing mitochondrial content does not protect from lipid-induced pathologies nor does it augment exercise adaptations. Physical activity ameliorates the effects of lipid overload-induced glucose intolerance, an effect that appears to be related to enhanced activation of autophagy. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.

PubMed

Ochodo, Eleanor A; Gopalakrishna, Gowri; Spek, Bea; Reitsma, Johannes B; van Lieshout, Lisette; Polman, Katja; Lamberton, Poppy; Bossuyt, Patrick M M; Leeflang, Mariska M G

2015-03-11

Point-of-care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014. We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. We included studies on participants residing in endemic areas only. Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random-effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). We included 90 studies; 88 from field settings in Africa. The median S. haematobium infection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards. Tests for S. haematobium Urine reagent test strips versus microscopyCompared to microscopy, the detection of microhaematuria on test strips had the highest sensitivity and specificity (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74 studies, 102,447 participants). For proteinuria, sensitivity was 61% and specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was 58% and specificity 61% (1532 participants). However, the difference in overall test accuracy between the urine reagent strips for microhaematuria and proteinuria was not found to be different when we compared separate populations (P = 0.25), or when direct comparisons within the same individuals were performed (paired studies; P = 0.21).When tests were evaluated against the higher quality reference standard (when multiple samples were analysed), sensitivity was marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs 61%). The specificity of these tests was comparable. Antigen assayCompared to microscopy, the CCA test showed considerable heterogeneity; meta-analytic sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to 100% (four studies, 901 participants). Tests for S. mansoni Compared to microscopy, the CCA test meta-analytic estimates for detecting S. mansoni at a single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a higher quality reference standard, the sensitivity results were comparable (89% vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity ranged from 47% to 94%, and specificity from 8% to 100% (4 studies, 1583 participants). Among the evaluated tests for S. haematobium infection, microhaematuria correctly detected the largest proportions of infections and non-infections identified by microscopy.The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy, but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection, possibly because the test is potentially more sensitive than microscopy.

Occurrence and Trends of Selected Chemical Constituents in Bottom Sediment, Grand Lake O' the Cherokees, Northeast Oklahoma, 1940-2008

USGS Publications Warehouse

Juracek, Kyle E.; Becker, Mark F.

2009-01-01

After over 100 years of continuous activity, lead and zinc mining in the Tri-State Mining District (hereafter referred to as the TSMD) in parts of southeast Kansas, southwest Missouri, and northeast Oklahoma ended in the 1970s. The mining activity resulted in substantial historical and ongoing input of cadmium, lead, and zinc to the environment including Grand Lake O' the Cherokees (hereafter referred to as Grand Lake), a large reservoir in northeast Oklahoma. To help determine the extent and magnitude of contamination in Grand Lake, a one-year study was conducted by the U.S. Geological Survey in cooperation with the U.S. Fish and Wildlife Service. Bottom-sediment coring at five sites was used to investigate the occurrence of cadmium, lead, zinc, and other selected constituents in the bottom sediment of Grand Lake. Cadmium concentrations in the bottom sediment of Grand Lake ranged from 2.3 to 3.6 mg/kg (milligrams per kilogram) with a median of 3.5 mg/kg (5 samples). Compared to an estimated local background concentration of 0.6 mg/kg, the historical mining activity increased cadmium concentrations by about 280 to 500 percent. Lead concentrations ranged from 35 to 102 mg/kg with a median of 59 mg/kg (50 samples). Compared to an estimated local background concentration of 20 mg/kg, the historical mining activity increased lead concentrations by about 75 to 410 percent. The range in zinc concentrations was 380 to 986 mg/kg with a median of 765 mg/kg (50 samples). Compared to an estimated local background concentration of 100 mg/kg, the historical mining activity increased zinc concentrations by about 280 to 890 percent. With the exception of the most upstream coring site, the lead and zinc depositional profiles generally were similar in terms of the range in concentrations measured and the temporal pattern observed. Depositional profiles for lead and zinc indicated mid-core peaks followed by concentrations that decreased since about the 1980s. The depositional profiles reflect the complex interaction of several factors including historical mining and related activities, mine drainage, remediation, landscape stabilization, precipitation and associated runoff, and the erosion and transport of contaminated and clean sediments within the basin. Compared to sediment-quality guidelines, the Grand Lake samples had cadmium concentrations that were substantially less than the general probable-effects concentration (PEC) (4.98 mg/kg) and a TSMD-specific PEC (11.1 mg/kg). The PECs represent the concentration above which toxic biological effects are likely to occur. Likewise, all sediment samples had lead concentrations that were substantially less than the general PEC (128 mg/kg) and a TSMD-specific PEC (150 mg/kg). Zinc concentrations typically exceeded the general PEC (459 mg/kg), but were substantially less than a TSMD-specific PEC (2,083 mg/kg). Throughout the history of Grand Lake, lead and zinc concentrations in the deposited sediment did not approach or exceed the TSMD-specific PECs. As of 2008, legacy effects of mining still included the delivery of contaminated sediment to Grand Lake by the Spring and Neosho Rivers. The Neosho River, with its larger flows and less-contaminated sediment, likely dilutes the load of contaminated sediment delivered to Grand Lake by the Spring River. The information contained in this report provides a baseline of Grand Lake conditions with which to compare future conditions that may represent a response to changes in mining-related activity in the Grand Lake Basin.

Impairment of Circulating CD4⁺CD25⁺GARP⁺ regulatory T cells in patients with acute coronary syndrome.

PubMed

Meng, Kai; Zhang, Wei; Zhong, Yucheng; Mao, Xiaobo; Lin, Yingzhong; Huang, Ying; Lang, Mingjian; Peng, Yudong; Zhu, Zhengfeng; Liu, Yuzhou; Zhao, Xiaoqi; Yu, Kunwu; Wu, Bangwei; Ji, Qingwei; Zeng, Qiutang

2014-01-01

Atherosclerosis (AS) is an inflammatory and immune disease. Regulatory T cells (Tregs) suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP) was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. To assess whether GARP(+) Tregs are downregulated in patients with acute coronary syndrome (ACS), we examined CD4(+)CD25(+)GARP(+) T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. Patients with ACS demonstrated a significant decrease in circulating CD4(+)CD25(+)GARP(+) Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA) or normal coronary artery (NCA). Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs) from patients with ACS exhibited a decrease in CD4(+)CD25(+)GARP(+) Tregs. These fnding indicate that circulating CD4(+)CD25(+)GARP(+) Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS. © 2014 S. Karger AG, Basel.

The Community Balance and Mobility Scale: A Pilot Study Detecting Impairments in Military Service Members With Comorbid Mild TBI and Psychological Health Conditions.

PubMed

Pape, Marcy M; Williams, Kathy; Kodosky, Paula N; Dretsch, Michael

2016-01-01

To compare the capacity of the Community Balance and Mobility Scale (CB&M) to identify balance and mobility deficits in Service Members (SMs) with mild traumatic brain injury and comorbid psychological health conditions (mTBI/PH) to other commonly used balance assessments. A clinical research institute that provides a 4-week, outpatient, interdisciplinary program for active-duty SMs with mTBI/PH. A nonrandomized, cross-sectional design that compared multiple measures between 2 groups-active duty SMs with (n = 8) and without (n = 8) the dual diagnosis of mTBI/PH. Gait speed, Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment (FGA), and CB&M to assess functional balance among the community-dwelling, TBI population. Across all measures, the mTBI/PH group performed significantly worse (P ≤ .01) with the exception of the FGA. The abilities of all objective measures to distinguish participants with mTBI/PH from healthy controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94). However, the CB&M showed the largest group differences in effect size (d = 2.6) and had the highest discriminate ability (AUC = 0.98; sensitivity 100%; specificity 88%). The CB&M appears to have higher sensitivity and specificity than other measures of balance in SMs with mTBI/PH. A higher cut score for the CB&M is needed for this population.

Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome

PubMed Central

2013-01-01

Background Phage-encoded serine integrases, such as φC31 integrase, are widely used for genome engineering. Fifteen such integrases have been described but their utility for genome engineering has not been compared in uniform assays. Results We have compared fifteen serine integrases for their utility for DNA manipulations in mammalian cells after first demonstrating that all were functional in E. coli. Chromosomal recombination reporters were used to show that seven integrases were active on chromosomally integrated DNA in human fibroblasts and mouse embryonic stem cells. Five of the remaining eight enzymes were active on extra-chromosomal substrates thereby demonstrating that the ability to mediate extra-chromosomal recombination is no guide to ability to mediate site-specific recombination on integrated DNA. All the integrases that were active on integrated DNA also promoted DNA integration reactions that were not mediated through conservative site-specific recombination or damaged the recombination sites but the extent of these aberrant reactions varied over at least an order of magnitude. Bxb1 integrase yielded approximately two-fold more recombinants and displayed about two fold less damage to the recombination sites than the next best recombinase; φC31 integrase. Conclusions We conclude that the Bxb1 and φC31 integrases are the reagents of choice for genome engineering in vertebrate cells and that DNA damage repair is a major limitation upon the utility of this class of site-specific recombinase. PMID:24139482

Strategies for Determining Correct Cytochrome P450 Contributions in Hepatic Clearance Predictions: In Vitro-In Vivo Extrapolation as Modelling Approach and Tramadol as Proof-of Concept Compound.

PubMed

T'jollyn, Huybrecht; Snoeys, Jan; Van Bocxlaer, Jan; De Bock, Lies; Annaert, Pieter; Van Peer, Achiel; Allegaert, Karel; Mannens, Geert; Vermeulen, An; Boussery, Koen

2017-06-01

Although the measurement of cytochrome P450 (CYP) contributions in metabolism assays is straightforward, determination of actual in vivo contributions might be challenging. How representative are in vitro for in vivo CYP contributions? This article proposes an improved strategy for the determination of in vivo CYP enzyme-specific metabolic contributions, based on in vitro data, using an in vitro-in vivo extrapolation (IVIVE) approach. Approaches are exemplified using tramadol as model compound, and CYP2D6 and CYP3A4 as involved enzymes. Metabolism data for tramadol and for the probe substrates midazolam (CYP3A4) and dextromethorphan (CYP2D6) were gathered in human liver microsomes (HLM) and recombinant human enzyme systems (rhCYP). From these probe substrates, an activity-adjustment factor (AAF) was calculated per CYP enzyme, for the determination of correct hepatic clearance contributions. As a reference, tramadol CYP contributions were scaled-back from in vivo data (retrograde approach) and were compared with the ones derived in vitro. In this view, the AAF is an enzyme-specific factor, calculated from reference probe activity measurements in vitro and in vivo, that allows appropriate scaling of a test drug's in vitro activity to the 'healthy volunteer' population level. Calculation of an AAF, thus accounts for any 'experimental' or 'batch-specific' activity difference between in vitro HLM and in vivo derived activity. In this specific HLM batch, for CYP3A4 and CYP2D6, an AAF of 0.91 and 1.97 was calculated, respectively. This implies that, in this batch, the in vitro CYP3A4 activity is 1.10-fold higher and the CYP2D6 activity 1.97-fold lower, compared to in vivo derived CYP activities. This study shows that, in cases where the HLM pool does not represent the typical mean population CYP activities, AAF correction of in vitro metabolism data, optimizes CYP contributions in the prediction of hepatic clearance. Therefore, in vitro parameters for any test compound, obtained in a particular batch, should be corrected with the AAF for the respective enzymes. In the current study, especially the CYP2D6 contribution was found, to better reflect the average in vivo situation. It is recommended that this novel approach is further evaluated using a broader range of compounds.

Passive fMRI mapping of language function for pediatric epilepsy surgical planning: validation using Wada, ECS, and FMAER.

PubMed

Suarez, Ralph O; Taimouri, Vahid; Boyer, Katrina; Vega, Clemente; Rotenberg, Alexander; Madsen, Joseph R; Loddenkemper, Tobias; Duffy, Frank H; Prabhu, Sanjay P; Warfield, Simon K

2014-12-01

In this study we validate passive language fMRI protocols designed for clinical application in pediatric epilepsy surgical planning as they do not require overt participation from patients. We introduced a set of quality checks that assess reliability of noninvasive fMRI mappings utilized for clinical purposes. We initially compared two fMRI language mapping paradigms, one active in nature (requiring participation from the patient) and the other passive in nature (requiring no participation from the patient). Group-level analysis in a healthy control cohort demonstrated similar activation of the putative language centers of the brain in the inferior frontal (IFG) and temporoparietal (TPG) regions. Additionally, we showed that passive language fMRI produced more left-lateralized activation in TPG (LI=+0.45) compared to the active task; with similarly robust left-lateralized IFG (LI=+0.24) activations using the passive task. We validated our recommended fMRI mapping protocols in a cohort of 15 pediatric epilepsy patients by direct comparison against the invasive clinical gold-standards. We found that language-specific TPG activation by fMRI agreed to within 9.2mm to subdural localizations by invasive functional mapping in the same patients, and language dominance by fMRI agreed with Wada test results at 80% congruency in TPG and 73% congruency in IFG. Lastly, we tested the recommended passive language fMRI protocols in a cohort of very young patients and confirmed reliable language-specific activation patterns in that challenging cohort. We concluded that language activation maps can be reliably achieved using the passive language fMRI protocols we proposed even in very young (average 7.5 years old) or sedated pediatric epilepsy patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI

PubMed Central

Chen, Yu-Chen; Chen, Huiyou; Jiang, Liang; Bo, Fan; Xu, Jin-Jing; Mao, Cun-Nan; Salvi, Richard; Yin, Xindao; Lu, Guangming; Gu, Jian-Ping

2018-01-01

Purpose: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. Methods: Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis. Results: Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus (PoCG). A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function involving the frontal lobe. Conclusions: Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the neuropathological mechanisms underlying presbycusis. PMID:29593512

Bovine brain pyroglutamyl aminopeptidase (type-1): purification and characterisation of a neuropeptide-inactivating peptidase.

PubMed

Cummins, P M; O'Connor, B

1996-08-01

Pyroglutamyl aminopeptidase type-1 (PAP-I) is reported to be a soluble, broad specificity aminopeptidase, capable of removing the pyroglutamic acid (pGlu) residue from the amino terminus of pGlu-peptides (e.g. TRH, LHRH, neurotensin and bombesin). The central aim of this study was to undertake, for the first time, the complete purification and characterisation of a PAP activity observed within the cytosolic fraction of bovine whole brain and to compare the properties of the enzyme with previous findings. A series of chromatographic steps (DEAE-Sepharose, Sephacryl S-200 and Activated Thiol Sepharose 4B) generated a soluble PAP activity purified to near homogeneity with a total active yield of 6.6% The enzyme displayed a native molecular mass of approximately 23,700 Da, which compares well with that value obtained under denaturing conditions via SDS-PAGE (24,000 Da), suggesting that the enzyme exists as a monomer. The expression of PAP activity displayed an absolute requirement for the presence of a disulphide bond-reducing agent such as DTT, whilst optimum activity was observed at pH 8.5. strong inhibition of PAP activity was observed with a number of different agents, including transition metal ions, sulphydryl-blocking agents and 2-pyrrolidone (a pGlu analog). A broad pyroglutamyl substrate specificity, which excludes substrates commencing with the pGlu-Pro bond, was also demonstrated for the bovine brain enzyme. Based on a comparison of these findings with those reported for PAP-I in other mammalian tissues, the soluble PAP activity observed in bovine whole brain can tentatively be classified as a pyroglutamyl aminopeptidase type-1 (EC 3.4.19.3).

Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells

PubMed Central

Yang, Jiayue; Waldron, Richard T.; Su, Hsin-Yuan; Moro, Aune; Chang, Hui-Hua; Eibl, Guido; Ferreri, Kevin; Kandeel, Fouad R.; Lugea, Aurelia; Li, Ling

2016-01-01

Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and hyperinsulinemia, the latter due to increased insulin secretion by pancreatic beta-cells. We reported that high-fat diet-induced PDAC progression in mice is associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic stellate cells (PaSC). We investigated here the effects of high concentrations of insulin and glucose on mouse and human PaSC growth and fibrosing responses. We found that compared with normal, pancreata from T2DM patients displayed extensive collagen deposition and activated PaSC in islet and peri-islet exocrine pancreas. Mice fed a high-fat diet for up to 12 mo similarly displayed increasing peri-islet fibrosis compared with mice fed control diet. Both quiescent and activated PaSC coexpress insulin (IR; mainly A type) and IGF (IGF-1R) receptors, and both insulin and glucose modulate receptor expression. In cultured PaSC, insulin induced rapid tyrosine autophosphorylation of IR/IGF-1R at specific kinase domain activation loop sites, activated Akt/mTOR/p70S6K signaling, and inactivated FoxO1, a transcription factor that restrains cell growth. Insulin did not promote activation of quiescent PaSC in either 5 mM or 25 mM glucose containing media. However, in activated PaSC, insulin enhanced cell proliferation and augmented production of extracellular matrix proteins, and these effects were abolished by specific inhibition of mTORC1 and mTORC2. In conclusion, our data support the concept that increased local glucose and insulin concentrations associated with obesity and T2DM promote PaSC growth and fibrosing responses. PMID:27609771

Field Trial of the CareStart Biosensor Analyzer for the Determination of Glucose-6-Phosphate Dehydrogenase Activity in Haiti.

PubMed

Weppelmann, Thomas A; von Fricken, Michael E; Wilfong, Tara D; Aguenza, Elisa; Philippe, Taina T; Okech, Bernard A

2017-10-01

Throughout many developing and tropical countries around the world, malaria remains a significant threat to human health. One barrier to malaria elimination is the ability to safely administer primaquine chemotherapy for the radical cure of malaria infections in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the current study, a field trial of the world's first quantitative, point-of-care assay for measuring G6PD activity was conducted in Haiti. The performance of the CareStart Biosensor Analyzer was compared with the gold standard spectrophotometric assay and genotyping of the G6PD allele in schoolchildren ( N = 343) from the Ouest Department of Haiti. In this population, 19.5% of participants (67/343) had some form of G6PD deficiency (< 60% residual activity) and 9.9% (34/343) had moderate-to-severe G6PD deficiency (< 30% residual activity). Overall, 18.95% of participants had the presence of the A-allele (65/343) with 7.87% (27/343) considered at high risk for drug-induced hemolysis (hemizygous males and homozygous females). Compared with the spectrophotometric assay, the sensitivity and specificity to determine participants with < 60% residual activity were 53.7% and 94.6%, respectively; for participants with 30% residual activity, the sensitivity and specificity were 5.9% and 99.7%, respectively. The biosensor overestimated the activity in deficient individuals and underestimated it in participants with normal G6PD activity, indicating the potential for a systematic measurement error. Thus, we suggest that the current version of the biosensor lacks adequate sensitivity and should be improved prior to its use as a point-of-care diagnostic for G6PD deficiency.

Novel fungal FAD glucose dehydrogenase derived from Aspergillus niger for glucose enzyme sensor strips.

PubMed

Sode, Koji; Loew, Noya; Ohnishi, Yosuke; Tsuruta, Hayato; Mori, Kazushige; Kojima, Katsuhiro; Tsugawa, Wakako; LaBelle, Jeffrey T; Klonoff, David C

2017-01-15

In this study, a novel fungus FAD dependent glucose dehydrogenase, derived from Aspergillus niger (AnGDH), was characterized. This enzyme's potential for the use as the enzyme for blood glucose monitor enzyme sensor strips was evaluated, especially by investigating the effect of the presence of xylose during glucose measurements. The substrate specificity of AnGDH towards glucose was investigated, and only xylose was found as a competing substrate. The specific catalytic efficiency for xylose compared to glucose was 1.8%. The specific activity of AnGDH for xylose at 5mM concentration compared to glucose was 3.5%. No other sugars were used as substrate by this enzyme. The superior substrate specificity of AnGDH was also demonstrated in the performance of enzyme sensor strips. The impact of spiking xylose in a sample with physiological glucose concentrations on the sensor signals was investigated, and it was found that enzyme sensor strips using AnGDH were not affected at all by 5mM (75mg/dL) xylose. This is the first report of an enzyme sensor strip using a fungus derived FADGDH, which did not show any positive bias at a therapeutic level xylose concentration on the signal for a glucose sample. This clearly indicates the superiority of AnGDH over other conventionally used fungi derived FADGDHs in the application for SMBG sensor strips. The negligible activity of AnGDH towards xylose was also explained on the basis of a 3D structural model, which was compared to the 3D structures of A. flavus derived FADGDH and of two glucose oxidases. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex-specific silencing of X-linked genes by Xist RNA

PubMed Central

Gayen, Srimonta; Maclary, Emily; Hinten, Michael; Kalantry, Sundeep

2016-01-01

X-inactive specific transcript (Xist) long noncoding RNA (lncRNA) is thought to catalyze silencing of X-linked genes in cis during X-chromosome inactivation, which equalizes X-linked gene dosage between male and female mammals. To test the impact of Xist RNA on X-linked gene silencing, we ectopically induced endogenous Xist by ablating the antisense repressor Tsix in mice. We find that ectopic Xist RNA induction and subsequent X-linked gene silencing is sex specific in embryos and in differentiating embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). A higher frequency of XΔTsixY male cells displayed ectopic Xist RNA coating compared with XΔTsixX female cells. This increase reflected the inability of XΔTsixY cells to efficiently silence X-linked genes compared with XΔTsixX cells, despite equivalent Xist RNA induction and coating. Silencing of genes on both Xs resulted in significantly reduced proliferation and increased cell death in XΔTsixX female cells relative to XΔTsixY male cells. Thus, whereas Xist RNA can inactivate the X chromosome in females it may not do so in males. We further found comparable silencing in differentiating XΔTsixY and 39,XΔTsix (XΔTsixO) ESCs, excluding the Y chromosome and instead implicating the X-chromosome dose as the source of the sex-specific differences. Because XΔTsixX female embryonic epiblast cells and EpiSCs harbor an inactivated X chromosome prior to ectopic inactivation of the active XΔTsix X chromosome, we propose that the increased expression of one or more X-inactivation escapees activates Xist and, separately, helps trigger X-linked gene silencing. PMID:26739568

The validity of activity monitors for measuring sleep in elite athletes.

PubMed

Sargent, Charli; Lastella, Michele; Halson, Shona L; Roach, Gregory D

2016-10-01

There is a growing interest in monitoring the sleep of elite athletes. Polysomnography is considered the gold standard for measuring sleep, however this technique is impractical if the aim is to collect data simultaneously with multiple athletes over consecutive nights. Activity monitors may be a suitable alternative for monitoring sleep, but these devices have not been validated against polysomnography in a population of elite athletes. Participants (n=16) were endurance-trained cyclists participating in a 6-week training camp. A total of 122 nights of sleep were recorded with polysomnography and activity monitors simultaneously. Agreement, sensitivity, and specificity were calculated from epoch-for-epoch comparisons of polysomnography and activity monitor data. Sleep variables derived from polysomnography and activity monitors were compared using paired t-tests. Activity monitor data were analysed using low, medium, and high sleep-wake thresholds. Epoch-for-epoch comparisons showed good agreement between activity monitors and polysomnography for each sleep-wake threshold (81-90%). Activity monitors were sensitive to sleep (81-92%), but specificity differed depending on the threshold applied (67-82%). Activity monitors underestimated sleep duration (18-90min) and overestimated wake duration (4-77min) depending on the threshold applied. Applying the correct sleep-wake threshold is important when using activity monitors to measure the sleep of elite athletes. For example, the default sleep-wake threshold (>40 activity counts=wake) underestimates sleep duration by ∼50min and overestimates wake duration by ∼40min. In contrast, sleep-wake thresholds that have a high sensitivity to sleep (>80 activity counts=wake) yield the best combination of agreement, sensitivity, and specificity. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment.

PubMed

Harrill, Joshua A; Freudenrich, Theresa; Wallace, Kathleen; Ball, Kenneth; Shafer, Timothy J; Mundy, William R

2018-04-05

Medium- to high-throughput in vitro assays that recapitulate the critical processes of nervous system development have been proposed as a means to facilitate rapid testing and identification of chemicals which may affect brain development. In vivo neurodevelopment is a complex progression of distinct cellular processes. Therefore, batteries of in vitro assays that model and quantify effects on a variety of neurodevelopmental processes have the potential to identify chemicals which may affect brain development at different developmental stages. In the present study, the results of concentration-response screening of 67 reference chemicals in a battery of high content imaging and microplate reader-based assays that evaluate neural progenitor cell proliferation, neural proginitor cell apoptosis, neurite initiation/outgrowth, neurite maturation and synaptogenesis are summarized and compared. The assay battery had a high degree of combined sensitivity (87%) for categorizing chemicals known to affect neurodevelopment as active and a moderate degree of combined specificity (71%) for categorizing chemicals not associated with affects on neurodevelopment as inactive. The combined sensitivity of the assay battery was higher compared to any individual assay while the combined specificity of the assay battery was lower compared to any individual assay. When selectivity of effects for a neurodevelopmental endpoint as compared to general cytotoxicity was taken into account, the combined sensitivity of the assay battery decreased (68%) while the combined specificity increased (93%). The identity and potency of chemicals identified as active varied across the assay battery, underscoring the need for use of a combination of diverse in vitro models to comprehensively screen chemicals and identify those which potentially affect neurodevelopment. Overall, these data indicate that a battery of assays which address many different processes in nervous system development may be used to identify potential developmental neurotoxicants and to distinguish specific from generalized cytotoxic effects with a high degree of success. Published by Elsevier Inc.

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.

[Substrate specifity in Amoeba proteus].

PubMed

Sopina, V A

2006-01-01

Three different phosphatases ("slow", "middle" and "fast") were found in Amoeba proteus (strain B) after PAGE and a subsequent gel staining in 1-naphthyl phosphate containing incubation mixture (pH 9.0). Substrate specificity of these phosphatases was determined in supernatants of homogenates using inhibitors of phosphatase activity. All phosphatases showed a broad substrate specificity. Of 10 tested compounds, p-nitrophenyl phosphate was a preferable substrate for all 3 phosphatases. All phosphatases were able to hydrolyse bis-p-nitrophenyl phosphate and, hence, displayed phosphodiesterase activity. All phosphatases hydrolysed O-phospho-L-tyrosine to a greater or lesser degree. Only little differences in substrate specificity of phosphatases were noticed: 1) "fast" and "middle" phosphatases hydrolysed naphthyl phosphates and O-phospho-L-tyrosine less efficiently than did "slow" phosphatase; 2) "fast" and "middle" phosphatases hydrolysed 2- naphthyl phosphate to a lesser degree than 1-naphthyl phosphate 3) "fast" and "middle" phosphatases hydrolysed O-phospho-L-serine and O-phospho-L-threonine with lower intensity as compared with "slow" phosphatase; 4) as distinct from "middle" and "slow" phosphatases, the "fast" phosphatase hydrolysed glucose-6-phosphate very poorly. The revealed broad substrate specificity of "slow" phosphatase together with data of inhibitory analysis and results of experiments with reactivation of this phosphatase by Zn2+-ions after its inactivation by EDTA strongly suggest that only the "slow" phosphatase is a true alkaline phosphatase (EC 3.1.3.1). The alkaline phosphatase of A. proteus is secreted into culture medium where its activity is low. The enzyme displays both phosphomono- and phosphodiesterase activities, in addition to supposed protein phosphatase activity. It still remains unknown, to which particular phosphatase class the amoeban "middle" and "fast" phosphatases (pH 9.0) may be assigned.

Microbiota diversity and gene expression dynamics in human oral biofilms

PubMed Central

2014-01-01

Background Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Results Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. Conclusions The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health. PMID:24767457

Microbiota diversity and gene expression dynamics in human oral biofilms.

PubMed

Benítez-Páez, Alfonso; Belda-Ferre, Pedro; Simón-Soro, Aurea; Mira, Alex

2014-04-27

Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be associated to dental health.

Automated Detector of High Frequency Oscillations in Epilepsy Based on Maximum Distributed Peak Points.

PubMed

Ren, Guo-Ping; Yan, Jia-Qing; Yu, Zhi-Xin; Wang, Dan; Li, Xiao-Nan; Mei, Shan-Shan; Dai, Jin-Dong; Li, Xiao-Li; Li, Yun-Lin; Wang, Xiao-Fei; Yang, Xiao-Feng

2018-02-01

High frequency oscillations (HFOs) are considered as biomarker for epileptogenicity. Reliable automation of HFOs detection is necessary for rapid and objective analysis, and is determined by accurate computation of the baseline. Although most existing automated detectors measure baseline accurately in channels with rare HFOs, they lose accuracy in channels with frequent HFOs. Here, we proposed a novel algorithm using the maximum distributed peak points method to improve baseline determination accuracy in channels with wide HFOs activity ranges and calculate a dynamic baseline. Interictal ripples (80-200[Formula: see text]Hz), fast ripples (FRs, 200-500[Formula: see text]Hz) and baselines in intracerebral EEGs from seven patients with intractable epilepsy were identified by experienced reviewers and by our computer-automated program, and the results were compared. We also compared the performance of our detector to four well-known detectors integrated in RIPPLELAB. The sensitivity and specificity of our detector were, respectively, 71% and 75% for ripples and 66% and 84% for FRs. Spearman's rank correlation coefficient comparing automated and manual detection was [Formula: see text] for ripples and [Formula: see text] for FRs ([Formula: see text]). In comparison to other detectors, our detector had a relatively higher sensitivity and specificity. In conclusion, our automated detector is able to accurately calculate a dynamic iEEG baseline in different HFO activity channels using the maximum distributed peak points method, resulting in higher sensitivity and specificity than other available HFO detectors.