Into the Curriculum.

ERIC Educational Resources Information Center

School Library Media Activities Monthly, 1996

1996-01-01

Provides five fully developed library media activities designed for use with specific curriculum units in art, health and nutrition, mathematics, science, and social studies. Library media skills, objectives, grade levels, instructional roles, procedures, evaluation, and follow-up are described for each activity. Specific topics include aardvarks,…

Light-regulated protein and mRNA synthesis in root caps of maize

NASA Technical Reports Server (NTRS)

Feldman, L. J.; Piechulla, B.; Sun, P. S.

1988-01-01

Illumination of maize roots initiates changes in mRNA levels and in the activities of proteins within the root cap. Using Northern analysis we showed a 5-6 fold increase in the levels of three specific mRNAs and a 14-fold increase in plastid mRNA. This increase is rapid, occurring within 30 minutes of illumination. With prolonged periods of darkness following illumination, messages return to levels observed in dark, control caps. For two species of mRNA illumination results in a reduction in message levels. Light-stimulated increases in the levels of specific mRNAs are proportionally greater than are increases in the activities of corresponding proteins. We suggest that the light-stimulated increase in protein activity in root caps may be preceded by and occur as a consequence of enhanced levels of mRNA. Our work suggests that photomorphogenesis in roots could involve changes in the levels of a wide variety of mRNAs within the root cap.

From the motor cortex to the movement and back again.

PubMed

Teka, Wondimu W; Hamade, Khaldoun C; Barnett, William H; Kim, Taegyo; Markin, Sergey N; Rybak, Ilya A; Molkov, Yaroslav I

2017-01-01

The motor cortex controls motor behaviors by generating movement-specific signals and transmitting them through spinal cord circuits and motoneurons to the muscles. Precise and well-coordinated muscle activation patterns are necessary for accurate movement execution. Therefore, the activity of cortical neurons should correlate with movement parameters. To investigate the specifics of such correlations among activities of the motor cortex, spinal cord network and muscles, we developed a model for neural control of goal-directed reaching movements that simulates the entire pathway from the motor cortex through spinal cord circuits to the muscles controlling arm movements. In this model, the arm consists of two joints (shoulder and elbow), whose movements are actuated by six muscles (4 single-joint and 2 double-joint flexors and extensors). The muscles provide afferent feedback to the spinal cord circuits. Cortical neurons are defined as cortical "controllers" that solve an inverse problem based on a proposed straight-line trajectory to a target position and a predefined bell-shaped velocity profile. Thus, the controller generates a motor program that produces a task-specific activation of low-level spinal circuits that in turn induce the muscle activation realizing the intended reaching movement. Using the model, we describe the mechanisms of correlation between cortical and motoneuronal activities and movement direction and other movement parameters. We show that the directional modulation of neuronal activity in the motor cortex and the spinal cord may result from direction-specific dynamics of muscle lengths. Our model suggests that directional modulation first emerges at the level of muscle forces, augments at the motoneuron level, and further increases at the level of the motor cortex due to the dependence of frictional forces in the joints, contractility of the muscles and afferent feedback on muscle lengths and/or velocities.

Serum interleukin measurement may help identify thyroid cancer patients with active disease.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Peres, Karina Colombera; Meneghetti, Murilo; Ward, Mirela Andrea Latham; Etchebehere, Elba Cristina Sá de Camargo; da Assumpção, Ligia Vera Montali; Ward, Laura Sterian

2018-02-01

Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Specifying the non-specific components of acupuncture analgesia

PubMed Central

Vase, Lene; Baram, Sara; Takakura, Nobuari; Yajima, Hiroyoshi; Takayama, Miho; Kaptchuk, Ted J.; Schou, Søren; Jensen, Troels Staehelin; Zachariae, Robert; Svensson, Peter

2014-01-01

It is well known that acupuncture has pain-relieving effects, but the contribution of specific and especially non-specific factors to acupuncture analgesia is less clear. One hundred and one patients who developed pain ≥ 3 on a visual analog scale (VAS, 0-10) following third molar surgery were randomized to receive active acupuncture, placebo acupuncture, or no treatment for 30 min with acupuncture needles with potential for double-blinding. Patients’ perception of the treatment (active or placebo), and expected pain levels (VAS) were assessed prior to and halfway through the treatment. Looking at actual treatment allocation, there was no specific effect of active acupuncture (P = 0.240), but a large and significant non-specific effect of placebo acupuncture (P < 0.001), which increased over time. Interestingly, however, looking at perceived treatment allocation, there was a significant effect of acupuncture (P < 0.001) indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture. Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings following both active and placebo acupuncture (up to 69.8%), This is the first study to show that under optimized blinding conditions non-specific factors such as patients’ perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self-reinforcing effects in acupuncture treatment To obtain an effect of acupuncture in clinical practice it may, therefore, be important to incorporate and optimize these factors. PMID:23707680

The twilight zone: ambient light levels trigger activity in primitive ants.

PubMed

Narendra, Ajay; Reid, Samuel F; Hemmi, Jan M

2010-05-22

Many animals become active during twilight, a narrow time window where the properties of the visual environment are dramatically different from both day and night. Despite the fact that many animals including mammals, reptiles, birds and insects become active in this specific temporal niche, we do not know what cues trigger this activity. To identify the onset of specific temporal niches, animals could anticipate the timing of regular events or directly measure environmental variables. We show that the Australian bull ant, Myrmecia pyriformis, starts foraging only during evening twilight throughout the year. The onset occurs neither at a specific temperature nor at a specific time relative to sunset, but at a specific ambient light intensity. Foraging onset occurs later when light intensities at sunset are brighter than normal or earlier when light intensities at sunset are darker than normal. By modifying ambient light intensity experimentally, we provide clear evidence that ants indeed measure light levels and do not rely on an internal rhythm to begin foraging. We suggest that the reason for restricting the foraging onset to twilight and measuring light intensity to trigger activity is to optimize the trade-off between predation risk and ease of navigation.

The twilight zone: ambient light levels trigger activity in primitive ants

PubMed Central

Narendra, Ajay; Reid, Samuel F.; Hemmi, Jan M.

2010-01-01

Many animals become active during twilight, a narrow time window where the properties of the visual environment are dramatically different from both day and night. Despite the fact that many animals including mammals, reptiles, birds and insects become active in this specific temporal niche, we do not know what cues trigger this activity. To identify the onset of specific temporal niches, animals could anticipate the timing of regular events or directly measure environmental variables. We show that the Australian bull ant, Myrmecia pyriformis, starts foraging only during evening twilight throughout the year. The onset occurs neither at a specific temperature nor at a specific time relative to sunset, but at a specific ambient light intensity. Foraging onset occurs later when light intensities at sunset are brighter than normal or earlier when light intensities at sunset are darker than normal. By modifying ambient light intensity experimentally, we provide clear evidence that ants indeed measure light levels and do not rely on an internal rhythm to begin foraging. We suggest that the reason for restricting the foraging onset to twilight and measuring light intensity to trigger activity is to optimize the trade-off between predation risk and ease of navigation. PMID:20129978

Expression of Bacillus protease (Protease BYA) from Bacillus sp. Y in Bacillus subtilis and enhancement of its specific activity by site-directed mutagenesis-improvement in productivity of detergent enzyme-.

PubMed

Tobe, Seiichi; Shimogaki, Hisao; Ohdera, Motoyasu; Asai, Yoshio; Oba, Kenkichi; Iwama, Masanori; Irie, Masachika

2006-01-01

An attempt was made to express protease BYA produced by an alkalophilic Bacillus sp. Y in Bacillus subtilis by gene engineering methods. The gene encoding protease BYA was cloned from Bacillus sp. Y, and expression vector pTA71 was constructed from the amylase promoter of Bacillus licheniformis, DNA fragments encoding the open reading frame of protease BYA, and pUB110. Protease BYA was secreted at an activity level of 5100 APU/ml in the common industrial culture medium of Bacillus subtilis transformed with pTA71. We then attempted to increase the specific activity of protease BYA by site-directed mutagenesis. Amino acid residue Ala29 next to catalytic Asp30 was replaced by one of three uncharged amino acid residues (Val29, Leu29, Ile29), and each mutant enzyme was expressed and isolated from the culture medium. Val29 mutant enzyme was secreted at an activity level of greater than 7000 APU/ml in culture medium, and its specific activity was 1.5-fold higher than that of the wild-type enzyme. Other mutant enzymes had specific activity similar to that of the original one and were less stabile than the wild-type enzyme. It can be thought that the substitution at amino acid residue 29 affects the level of activity and stability of protease BYA.

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.

Sandwich masking eliminates both visual awareness of faces and face-specific brain activity through a feedforward mechanism.

PubMed

Harris, Joseph A; Wu, Chien-Te; Woldorff, Marty G

2011-06-07

It is generally agreed that considerable amounts of low-level sensory processing of visual stimuli can occur without conscious awareness. On the other hand, the degree of higher level visual processing that occurs in the absence of awareness is as yet unclear. Here, event-related potential (ERP) measures of brain activity were recorded during a sandwich-masking paradigm, a commonly used approach for attenuating conscious awareness of visual stimulus content. In particular, the present study used a combination of ERP activation contrasts to track both early sensory-processing ERP components and face-specific N170 ERP activations, in trials with versus without awareness. The electrophysiological measures revealed that the sandwich masking abolished the early face-specific N170 neural response (peaking at ~170 ms post-stimulus), an effect that paralleled the abolition of awareness of face versus non-face image content. Furthermore, however, the masking appeared to render a strong attenuation of earlier feedforward visual sensory-processing signals. This early attenuation presumably resulted in insufficient information being fed into the higher level visual system pathways specific to object category processing, thus leading to unawareness of the visual object content. These results support a coupling of visual awareness and neural indices of face processing, while also demonstrating an early low-level mechanism of interference in sandwich masking.

Sport-specific outcomes after anterior cruciate ligament reconstruction.

PubMed

Warner, Stephen J; Smith, Matthew V; Wright, Rick W; Matava, Matthew J; Brophy, Robert H

2011-08-01

Although anterior cruciate ligament (ACL) reconstruction has been studied extensively in the literature, sport-specific outcomes have not been well-documented. The purpose of this systematic review was to assess sport-specific outcomes after ACL reconstruction in the literature. We performed a systematic review of the literature to identify studies reporting sport-specific outcomes after primary ACL reconstruction. Included studies were required to have reported standardized outcomes after primary ACL reconstruction for a single sport or comparing between different sports. In total 8 studies conformed to all inclusion criteria: 2 Level II studies, 1 Level III study, and 5 Level IV case series. Only 1 study reported comparisons of standardized outcomes between different sports, whereas 7 studies reported standardized outcomes in a single sport. Return to activity was the most common sport-specific outcome reported and varied from 19% (soccer) to 100% (bicycling and rugby), although the methods of measuring this outcome differed. Whereas return to activity after ACL reconstruction appears more likely for bicycling and jogging than for cutting and pivoting sports such as soccer and football, the literature on sport-specific outcomes from ACL reconstruction is limited with minimal data. Further studies are needed to report sport-specific outcomes and return to play after ACL reconstruction. Level IV, systematic review of Level II, III, and IV studies. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

White blood cell counts mediate the effects of physical activity on prostate-specific antigen levels.

PubMed

Loprinzi, Paul D; Richart, Sarah M

2014-09-01

The purpose of this study was to examine whether white blood cell (WBC) level mediated the relationship between physical activity and prostate-specific antigen (PSA) levels. Data from the 2003-2006 National Health and Nutrition Examination Survey were used; 1,726 U.S. adult men (aged 40 years or older) provided complete data on the study variables. Participants wore an ActiGraph 7164 accelerometer for a 7-day period to measure their physical activity behavior, and PSA and WBC levels were obtained from a blood sample. After adjustments, results showed that moderate-to-vigorous physical activity (MVPA) was inversely associated with WBC count (b = - .03; 95% CI [ - 0.04, - 0.006; p = .01), and WBC count (b = .10; 95% CI [0.009, 0.18; p = .04) was positively associated with PSA. Both the Sobel (coef. = - .004, SE = .002; z = - 2.0; p = .03) and the Aroian (coef. = - .004, SE = .002; z = - 1.9; p = .03) tests demonstrated that WBC mediated the relationship between physical activity and PSA. Additionally, among 107 participants with prostate cancer, survivors engaging in more MVPA had lower levels of WBC (b = - .04; 95% CI [ - 0.09, - 0.0009; p = .04). Conclusion Physical activity may influence PSA levels through WBC modulation; however, future research is needed to determine the direction of causality. Additionally, prostate cancer survivors engaging in higher levels of MVPA had lower levels of WBC, underscoring the importance of promoting physical activity among prostate cancer survivors.

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.

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

PubMed Central

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

2016-01-01

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

Anterior temporal cortex and semantic memory: reconciling findings from neuropsychology and functional imaging.

PubMed

Rogers, Timothy T; Hocking, Julia; Noppeney, Uta; Mechelli, Andrea; Gorno-Tempini, Maria Luisa; Patterson, Karalyn; Price, Cathy J

2006-09-01

Studies of semantic impairment arising from brain disease suggest that the anterior temporal lobes are critical for semantic abilities in humans; yet activation of these regions is rarely reported in functional imaging studies of healthy controls performing semantic tasks. Here, we combined neuropsychological and PET functional imaging data to show that when healthy subjects identify concepts at a specific level, the regions activated correspond to the site of maximal atrophy in patients with relatively pure semantic impairment. The stimuli were color photographs of common animals or vehicles, and the task was category verification at specific (e.g., robin), intermediate (e.g., bird), or general (e.g., animal) levels. Specific, relative to general, categorization activated the antero-lateral temporal cortices bilaterally, despite matching of these experimental conditions for difficulty. Critically, in patients with atrophy in precisely these areas, the most pronounced deficit was in the retrieval of specific semantic information.

META-ANALYSIS OF PHYSICAL ACTIVITY LEVEL ( PAL ) DATA FOR U.S. YOUTH

EPA Science Inventory

This paper describes analytical research undertaken by EMRB staff to obtain age- and gender-specific distributions of Physical Activity Level (PAL) values for children measured in studies published between 1990-2004 in the clinical nutrition and exercise physiology literatures. ...

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.

The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity.

PubMed

Sun, Yang; Zhu, Xiaoyan; Chen, Xufeng; Liu, Haifeng; Xu, Yu; Chu, Yajing; Wang, Gang; Liu, Xiaolong

2014-10-10

T-cell activation is critical for successful immune responses and is controlled at multiple levels. Although many changes of T-cell receptor-associated signalling molecules affect T-cell activation, the transcriptional mechanisms that control this process remain largely unknown. Here we find that T cell-specific deletion of the mediator subunit Med23 leads to hyperactivation of T cells and aged Med23-deficient mice exhibit an autoimmune syndrome. Med23 specifically and consistently promotes the transcription of multiple negative regulators of T-cell activation. In the absence of Med23, the T-cell activation threshold is lower, which results in enhanced antitumour T-cell function. Cumulatively, our data suggest that Med23 contributes to controlling T-cell activation at the transcriptional level and prevents the development of autoimmunity.

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Humoral and cellular responses to casein in patients with food protein-induced enterocolitis to cow's milk.

PubMed

Caubet, Jean Christoph; Bencharitiwong, Ramon; Ross, Andrew; Sampson, Hugh A; Berin, M Cecilia; Nowak-Węgrzyn, Anna

2017-02-01

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy manifesting within 1 to 4 hours of food ingestion with repetitive emesis and lethargy. We sought to characterize immune responses to casein in children with FPIES caused by cow's milk (CM). Total IgE and IgM, CM-specific IgG, and casein-specific IgE, IgG, IgG 4 , and IgM levels, as well as immunoglobulin free light chains, were measured in both patients with active and those with resolved CM-FPIES. Proliferating casein/T-effector cell counts were measured in children with CM-FPIES, children with IgE-mediated CM allergy, and those tolerating CM. Cytokine concentrations in the supernatants were quantified. Serum cytokine and tryptase levels were measured before and after a positive oral food challenge (OFC) result and compared with levels in those with a negative OFC result. We found low levels of CM and casein-specific IgG and casein-specific IgG 4 in patients with CM-FPIES versus those tolerating CM (P < .05). Although we found both a high CD4 + T cell-proliferative response and T H 2 cytokines production after casein stimulation in children with CM-FPIES, results were similar to those in control subjects. Significantly lower secretion of IL-10 and higher secretion of IL-9 by casein-stimulated T cells were found in patients with CM-FPIES versus those with IgE-mediated CM allergy. Lower baseline serum levels of IL-10 and higher tryptase levels were found in active CM-FPIES versus resolved CM-FPIES. We found a significant increase in serum IL-10 and IL-8 levels after a positive OFC result. We confirm the paucity of humoral response in patients with CM-FPIES. IL-10 might play a key role in acquisition of tolerance in patients with CM-FPIES. Increased serum IL-8 levels in patients with active FPIES suggest neutrophil involvement. Elevated baseline serum tryptase levels in patients with active FPIES suggest low-grade intestinal mast cell activation or increased mast cell load. Copyright © 2016. Published by Elsevier Inc.

Ocular toxoplasmosis: evaluation of lacrimal-specific secretory IgA levels in both patients with active and inactive phases of the disease.

PubMed

Lynch, Luiz Felipe; Lynch, Maria Isabel; Ferreira, Rodrigo Santana do Nascimento; Vasconcelos, Mirelle Souza Leão; Melo, Narjara; Ferreira, Silvana; Malagueño, Elizabeth

2011-08-01

Ocular toxoplasmosis can result in recurrent uveitis. Studies have shown that a correlation between active ocular toxoplasmosis and the presence of anti-Toxoplasma gondii secretory IgA (SIgA) in tears. This study compares anti-T. gondii SIgA levels in patients' tears during the acute and inactive phases of toxoplasmic uveitis. Twenty-nine positive tear specific SIgA for T. gondii patients with acute toxoplasmic uveitis were selected and were followed-up for at least two years, when the anti-T. gondii SIgA tears levels were determined. Specific SIgA for T. gondii was negative in 22 patients (75.86%) and positive in seven patients (24.13%) of whom six (85.7%) were followed over three years. Average SIgA levels during the acute phase are 1.54 and decrease significantly to 0.72 (p = 0.0001) during the inactive phase of disease. Because anti-T. gondii SIgA in the tear is negative in 75.86% of patients after the acute phase of infection, T. gondii SIgA levels may be used as a complementary diagnostic marker for active ocular toxoplasmosis.

The Role of Exergaming in Improving Physical Activity: A Review

PubMed Central

Sween, Jennifer; Wallington, Sherrie Flynnt; Sheppard, Vanessa; Taylor, Teletia; Llanos, Adana A.; Adams-Campbell, Lucile Lauren

2013-01-01

Background The high prevalence of obesity in America can be attributed to inadequate energy expenditure as a result of high levels of physical inactivity. This review presents an overview of the current literature on physical activity, specifically through active videogame systems (exergaming) and how these systems can help to increase physical activity levels. Methods The search strategy for this review was to identify previous studies which investigated energy expenditure levels using a single active video game or a combination of active videogames. Results Based on data from 27 studies, a strong correlation exists between exergaming and increased energy expenditure (up to 300% above resting levels). The majority of active videogames tested were found to achieve physical activity levels of moderate intensity, which meet American College of Sports Medicine guidelines for health and fitness. Conclusions Exergaming is a new and exciting strategy to potentially improve physical activity levels and reduce obesity among Americans. PMID:25078529

Prediction of isometric motor tasks and effort levels based on high-density EMG in patients with incomplete spinal cord injury

NASA Astrophysics Data System (ADS)

Jordanić, Mislav; Rojas-Martínez, Mónica; Mañanas, Miguel Angel; Francesc Alonso, Joan

2016-08-01

Objective. The development of modern assistive and rehabilitation devices requires reliable and easy-to-use methods to extract neural information for control of devices. Group-specific pattern recognition identifiers are influenced by inter-subject variability. Based on high-density EMG (HD-EMG) maps, our research group has already shown that inter-subject muscle activation patterns exist in a population of healthy subjects. The aim of this paper is to analyze muscle activation patterns associated with four tasks (flexion/extension of the elbow, and supination/pronation of the forearm) at three different effort levels in a group of patients with incomplete Spinal Cord Injury (iSCI). Approach. Muscle activation patterns were evaluated by the automatic identification of these four isometric tasks along with the identification of levels of voluntary contractions. Two types of classifiers were considered in the identification: linear discriminant analysis and support vector machine. Main results. Results show that performance of classification increases when combining features extracted from intensity and spatial information of HD-EMG maps (accuracy = 97.5%). Moreover, when compared to a population with injuries at different levels, a lower variability between activation maps was obtained within a group of patients with similar injury suggesting stronger task-specific and effort-level-specific co-activation patterns, which enable better prediction results. Significance. Despite the challenge of identifying both the four tasks and the three effort levels in patients with iSCI, promising results were obtained which support the use of HD-EMG features for providing useful information regarding motion and force intention.

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.

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.

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.

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

PubMed

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

2004-09-15

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

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.

[Validity of a standard questionnaire to assess physical activity for specific medical checkups and health guidance].

PubMed

Kawakami, Ryoko; Miyachi, Motohiko

2010-10-01

This study aimed to determine the validity of a standard questionnaire to assess amount of physical activity (PA) and cardiorespiratory fitness (VO2peak). A total of 483 men and women, aged 20 to 69 years, participated. The standard questionnaire included 3 items about exercise, PA, and walking speed. All questions were designed to require an answer of Yes or No. Subjects were classified into one of four groups regarding the number of Yes answers to the three questions, giving activity levels of 0 to 3. The amount of PA was measured objectively with a tn-axial accelerometer which could also calculate daily step counts, and the amounts of PA under 3 metabolic equivalents (METs) and at 3 METs or more. VO2peak. was measured by incremental cycle exercise tests with indirect calorimetry. The daily step counts, the amount of PA at 3 METs or more, and the VO2peak. were significantly higher in subjects who answered Yes to each question than in those who answered No. Sensitivity and specificity of each question were 62-73% and 45-71% for the amount of PA established with the "Exercise and Physical Activity Reference for Health Promotion 2006 (EPAR2006)". The sum of sensitivity and specificity was the highest when the cutoff value was activity level 2 (sensitivity 73%, specificity 68%). Sensitivity and specificity for VO2max established by EPAR2006 were lower than those for the amount of PA. These results suggest that only answering simple questions with a standard questionnaire is sufficient for estimation of PA levels for specific medical checkups and health guidance, even though the accuracy is somewhat limited.

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

PubMed

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

2018-04-02

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

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus.

PubMed

Liu, Chau-Ching; Manzi, Susan; Kao, Amy H; Navratil, Jeannine S; Ruffing, Margie J; Ahearn, Joseph M

2005-10-01

There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activation-derived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE. We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity. A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross-sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA-SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients. These findings support our hypothesis that C4d-bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE.

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.

Determination of antibody to Streptococcus mutans from radiation-induced xerostomia patients. Agglutination activity against cariogenic microorganisms, active immunoglobulin classes, and post-irradiation caries activity in cancer patients. Final report 15 jul 77-14 apr 79

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

Brown, L.R.; O'Neill, P.A.; Dreizen, S.

1979-07-01

The relationship between specific agglutination (Ag) and caries activity during 30 month post radiation was assessed in 36 head and neck cancer patients. Ag titers in 444 saliva and 481 serum samples from these patients and 16 noncancer controls were determined against formalinized cellular antigens of Streptococcus mutans (Sm), Streptococcus sanguis (Ss), Streptococcus mitis, Lactobacillus fermenti (Lf), and Lactobacillus casei. Saliva IgA and IgG levels and Ag titers were significantly higher in cancer patients than in noncancer controls. Post radiation-induced xerostomic changes in saliva IgA reflected changes in specific Ag against oral microbes, particularly Sm serotype c. Patients with highmore » saliva IgA levels had significantly higher saliva Ag titers to Sm, Ss and Lf, lower plaque Sm counts and lower caries activity than patients with low saliva IgA levels. Serum Ag titers, however, showed no significant relationship with either serum Ig levels, microbial counts or caries activity. Chromatographic separation of Ig classes showed that Ag activity in saliva stemmed mainly from secretory IgA. Most serum Ag activity was found in regions corresponding to IgG and 7S IgA.« less

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

PubMed Central

Lee, Rachel S.; House, Colin M.; Cristiano, Briony E.; Hannan, Ross D.; Pearson, Richard B.; Hannan, Katherine M.

2011-01-01

The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ. PMID:21869924

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.

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.

Predictors of participation in sports after hip and knee arthroplasty.

PubMed

Williams, Daniel H; Greidanus, Nelson V; Masri, Bassam A; Duncan, Clive P; Garbuz, Donald S

2012-02-01

While the primary objective of joint arthroplasty is to improve patient quality of life, pain, and function, younger active patients often demand a return to higher function that includes sporting activity. Knowledge of rates and predictors of return to sports will help inform expectations in patients anticipating return to sports after joint arthroplasty. We measured the rate of sports participation at 1 year using the UCLA activity score and explored 11 variables, including choice of procedure/prosthesis, that might predict return to a high level of sporting activity, when controlling for potential confounding variables. We retrospectively evaluated 736 patients who underwent primary metal-on-polyethylene THA, metal-on-metal THA, hip resurfacing arthroplasty, revision THA, primary TKA, unicompartmental knee arthroplasty, and revision TKA between May 2005 and June 2007. We obtained UCLA activity scores on all patients; we defined high activity as a UCLA score of 7 or more. We evaluated patient demographics (age, sex, BMI, comorbidity), quality of life (WOMAC score, Oxford Hip Score, SF-12 score), and surgeon- and procedural/implant-specific variables to identify factors associated with postoperative activity score. Minimum followup was 11 months (mean, 12.1 months; range, 11-13 months). Preoperative UCLA activity score, age, male sex, and BMI predicted high activity scores. The type of operation and implant characteristics did not predict return to high activity sports. Our data suggest patient-specific factors predict postoperative activity rather than factors specific to type of surgery, implant, or surgeon factors. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

[Specific humoral immunity after single immunization with mumps vaccine: data of a 3-year follow-up].

PubMed

Otrashevskaia, A V; Bukin, E K; Krasil'nikov, I V; Ignat'ev, G M

2011-01-01

The level and spectrum of humoral specific immunity were studied in 60 volunteers immunized with Russian mumps vaccine. Specific IgG levels were measured by enzyme immunoassay (EIA) and neutralization test using the Leningrad-3 (L-3) mumps virus (MV) vaccine strain and 5 heterologous MV strains of various genotypes (A, B, C, D, and H). The maximum functional activity of antibodies was recorded at an average of 18 months postvaccination. Within 3 years after vaccination, starting at 6 months, specific IgG neutralized all 6 MV strains having varying activity in relation to the genotype. Neutralizing titers (NT) against the L-3 strain were 1.3-1.7-fold higher than those against heterologous MV strains throughout the follow-up. Despite a tendency towards lower specific IgG levels, within 3 years postvaccination, EIA IgG titers remained to be 2.5 -log, L-3 strain HT were -log, or more, and the titers against 5 heterologous MV strains were 2 -log2 or more in all the volunteers.

Mediating Effects of Self-Efficacy, Benefits and Barriers on the Association between Peer and Parental Factors and Physical Activity among Adolescent Girls with a Lower Educational Level.

PubMed

Verloigne, Maite; Cardon, Greet; De Craemer, Marieke; D'Haese, Sara; De Bourdeaudhuij, Ilse

2016-01-01

The prevalence of physical activity among lower educated adolescent girls is low, suggesting it is important to have insights into the complex processes that may underlie their physical activity levels. Therefore, this study aimed to examine the mediating effects of self-efficacy, perceived benefits and barriers on the associations between peer and parental variables and physical activity among lower educated adolescent girls. In total, 226 girls (mean age 16.0±1.0 years; 53% technical education; 47% vocational education) from a convenience sample of 6 secondary schools in Flanders, Belgium, completed a questionnaire on their total physical activity level and related peer and parental variables (i.e. modeling of physical activity, co-participation in physical activities and encouragement to be active) and personal variables (i.e. self-efficacy to be active, and specific perceived benefits of physical activity and specific barriers to be active). Mediating effects were tested using MacKinnon's product-of-coefficients test based on multilevel linear regression analyses. Higher peer and parental modeling, co-participation and encouragement were significantly related to a higher physical activity level among adolescent girls (p<0.05). Self-efficacy, the perceived benefits of having fun, being around friends or meeting new people, and not being bored and the perceived barrier of not liking physical activity mediated several associations between peer and parental variables and girls' physical activity, with some of the mediated proportions exceeding 60%. This study contributed to a better understanding of the complexity of how parental and peer factors work together with personal factors to influence the physical activity levels of adolescent girls with a lower educational level. Interventions should involve both peers and parents, as they may influence girls' physical activity both directly and indirectly through the internalisation of several personal variables, such as self-efficacy to be active and the perceived benefit of having fun.

Identification of predictor parameters to determine agro-industrial compost suppressiveness against Fusarium oxysporum and Phytophthora capsici diseases in muskmelon and pepper seedlings.

PubMed

Blaya, Josefa; Lloret, Eva; Ros, Margarita; Pascual, Jose Antonio

2015-05-01

The lack of reliable prediction tools for evaluation of the level and specificity of compost suppressiveness limits its application. In our study, different chemical, biological and microbiological parameters were used to evaluate their potential use as a predictor parameter for the suppressive effect of composts against Fusarium oxysporum f. sp. melonis (FOM) and Phytophthora capsici (P. capsici) in muskmelon and pepper seedlings respectively. Composts were obtained from artichoke sludge, chopped vineyard pruning waste and various agro-industrial wastes (C1: blanched artichokes; C2: garlic waste; C3: dry olive cake). Compost C3 proved to offer the highest level of resistance against FOM, and compost C2 the highest level of resistance against P. capsici. Analysis of phospholipid fatty acids isolated from compost revealed that the three composts showed different microbial community structures. Protease, NAGase and chitinase activities were significantly higher in compost C3, as was dehydrogenase activity in compost C2. The use of specific parameters such as general (dehydrogenase activity) and specific enzymatic activities (protease, NAGase and chitinase activities) may be useful to predict compost suppressiveness against both pathogens. The selection of raw materials for agro-industrial composts is important in controlling Fusarium wilt and Phytophthora root rot. © 2014 Society of Chemical Industry.

Tissue-specific bioaccumulation and oxidative stress responses in juvenile Japanese flounder ( Paralichthys olivaceus) exposed to mercury

NASA Astrophysics Data System (ADS)

Huang, Wei; Cao, Liang; Ye, Zhenjiang; Lin, Longshan; Chen, Quanzhen; Dou, Shuozeng

2012-07-01

To understand mercury (Hg) toxicity in marine fish, we measured Hg accumulation in juvenile Japanese flounder ( Paralichthys olivaceus) and assessed the effects on growth and antioxidant responses. After Hg exposure (control, 5, 40, and 160 μg/L Hg) for 28 d, fish growth was significantly reduced. The accumulation of Hg in fish was dose-dependent and tissue-specific, with the maximum accumulation in kidney and liver, followed by gills, bone, and muscle. Different antioxidants responded differently to Hg exposure to cope with the induction of lipid peroxidation (LPO), which was also tissue-specific and dosedependent. As Hg concentration increased, superoxide dismutase (SOD) and catalase (CAT) activities increased significantly, whereas glutathione S -transferase (GST) activity and glutathione (GSH) levels decreased significantly in the gills. SOD and glutathione peroxidase (GPx) activities and the GSH level increased significantly in the liver. SOD activity and GSH levels increased significantly, but CAT activity decreased significantly with an increase in Hg concentration in the kidney. LPO was induced significantly by elevated Hg in the gills and kidney but was least affected in the liver. Therefore, oxidative stress biomarkers in gills were more sensitive than those in the liver and kidney to Hg exposure. Thus, the gills have potential as bioindicators for evaluating Hg toxicity in juvenile flounder.

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.

Gender and Facebook motives as predictors of specific types of Facebook use: A latent growth curve analysis in adolescence.

PubMed

Frison, Eline; Eggermont, Steven

2016-10-01

Despite increasing evidence that specific types of Facebook use (i.e., active private, active public, and passive Facebook use) are differently related to adolescents' well-being, little is known how these types function over the course of adolescence and whether gender and Facebook motives may predict the initial level and changes in these types over time. To address these gaps, Flemish adolescents (ages 12-19) were questioned at three different time points, with six months in between (NTime1 = 1866). Latent growth curve models revealed that active private Facebook use increased over the course of adolescence, whereas public Facebook use decreased. Passive Facebook use, however, remained stable. In addition, gender and Facebook motives were related to initial levels of specific types of Facebook use, and predictive of dynamic change in specific types of Facebook use over time. The discussion focuses on the understanding and implications of these findings. Copyright © 2016. Published by Elsevier Ltd.

A positive feedback at the cellular level promotes robustness and modulation at the circuit level

PubMed Central

Dethier, Julie; Drion, Guillaume; Franci, Alessio

2015-01-01

This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation. PMID:26311181

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.

Technology and equipment based on induction melters with ``cold'' crucible for reprocessing active metal waste

NASA Astrophysics Data System (ADS)

Pastushkov, V. G.; Molchanov, A. V.; Serebryakov, V. P.; Smelova, T. V.; Shestoperov, I. N.

2000-07-01

The paper discusses specific features of technology, equipment and control of a single stage RAMW decontamination and melting process in an induction furnace equipped with a "cold" crucible. The calculated and experimental data are given on melting high activity level stainless steel and Zr simulating high activity level metal waste. The work is under way in SSC RF VNIINM.

A Balancing Act in the Third Space: Graduate-Level Earth Science in an Urban Teacher-Residency Program

ERIC Educational Resources Information Center

Zirakparvar, N. Alex

2015-01-01

This article describes a museum-based urban teacher-residency (UTR) program's approach to building subject-specific content knowledge and research experience in Earth Science teacher candidates. In the museum-based program, graduate-level science courses and research experiences are designed and implemented specifically for the UTR by active Earth…

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

PubMed

Rondaan, C; van Leer, C C; van Assen, S; Bootsma, H; de Leeuw, K; Arends, S; Bos, N A; Westra, J

2018-07-01

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Engineering of the institutionalization of the circular economy at the level of casting production

NASA Astrophysics Data System (ADS)

Vescan, M. M.; Soporan, V. F.; Crișan, D. M.; Lehene, T. R.; Pădurețu, S.; Samuila, V.

2017-06-01

This paper is motivated by the necessity of introducing the principles of circular economy at the level of different social - economic activities, and from this point of view one of the fields with a special potential is that of the manufacture of castings. Objective: to connect to the organizing and application of the methodology of the circular economy principles. The proposed method is an innovating one, being connected to the use of institutionalization engineering. Formulating the subject: The subject formulated to be solved aims at the introduction of new approaches, defined through institutionalization engineering, which proposes to set the correlation of actions between the specifics of the circular economy and the specific elements of the manufacture of castings. Research method: An institutional structuring operation was imposed for the optimization of the research method, in which different versions interact at the following levels: the level of public policies, the level of the regulatory framework, the level of technical solutions and the level of financing solutions and financial instruments. The determination of the optimal solution established in a dynamic context, favorable for the requirements of the different actors present within the process, appeals to the elements of critical thinking, specific for the engineer’s actions. Achievement of the research activity: The research activity structures a methodology of quantifying the contributions of each stage of the manufacturing process for castings at the fulfilling of the specific conditions of the circular economy, indicating the critical areas of action for more efficient actions of the circular economy, according to the market economy requirements, where there is a potential of implementing the technical solutions by quantizing the financial solutions and the opportunity of using the financial instruments. The major contribution of the research: The proposed methodology, with examples at the level of castings manufacture, sets the bases of a new field of action of the engineering thinking, namely, that of circular economy institutionalization functioning. Conclusions of the research activity: The proposed methodology represents the bases of establishing a new instrument of action at the level of institutionalized functioning of the circular economy.

Enhanced functional stability of plasminogen activator inhibitor-1 in patients with livedoid vasculopathy.

PubMed

Agirbasli, Mehmet; Eren, Mesut; Eren, Fatih; Murphy, Sheila B; Serdar, Zehra A; Seckin, Dilek; Zara, Tuba; Cem Mat, M; Demirkesen, Cuyan; Vaughan, Douglas E

2011-07-01

Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, and anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was established as cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion suggesting that inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 antigen (Ag) and activity levels in 20 patients with biopsy proven LV (mean age 26 ± 11, M/F = 7/13, median disease duration 3.5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 14 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 Ag and activity levels were measured at 9 AM in all patients. Both Ag (34 (26) ng/ml) (median (interquartile range)) and specific activity (17 (23) IU/fmole) levels of PAI-1 were moderately elevated in LV patients compared to the controls, however, PAI-1 kinetic studies demonstrated markedly enhanced stability of PAI-1 activity in plasma from patients with LV. Specific activity at 16 h was significantly higher than expected specific activity levels (7 (11) vs. 0.07 (0.09) IU/fmole, P < 0.01). While the exact mechanism of increased stability of PAI-1 activity is not known, it may be due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, and systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative in patients with LV.

Benchmark studies of induced radioactivity produced in LHC materials, Part I: Specific activities.

PubMed

Brugger, M; Khater, H; Mayer, S; Prinz, A; Roesler, S; Ulrici, L; Vincke, H

2005-01-01

Samples of materials which will be used in the LHC machine for shielding and construction components were irradiated in the stray radiation field of the CERN-EU high-energy reference field facility. After irradiation, the specific activities induced in the various samples were analysed with a high-precision gamma spectrometer at various cooling times, allowing identification of isotopes with a wide range of half-lives. Furthermore, the irradiation experiment was simulated in detail with the FLUKA Monte Carlo code. A comparison of measured and calculated specific activities shows good agreement, supporting the use of FLUKA for estimating the level of induced activity in the LHC.

Influence of acute and chronic administration of methadone hydrochloride on NADPH-cytochrome c reductase and cytochrome P-450 of mouse liver microsomes.

PubMed

Datta, R K; Johnson, E A; Bhattacharjee, G; Stenger, R J

1976-03-01

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH-cytochrome c reductase and did not change much the content of cytochrome P-450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P-450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P-450, but with higher doses of methadone, the content of P-450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P-450 content returned to normal about two weeks after discontinuation of methadone administration.

Ferromagnetic interaction model of activity level in workplace communication

NASA Astrophysics Data System (ADS)

Akitomi, Tomoaki; Ara, Koji; Watanabe, Jun-ichiro; Yano, Kazuo

2013-03-01

The nature of human-human interaction, specifically, how people synchronize with each other in multiple-participant conversations, is described by a ferromagnetic interaction model of people’s activity levels. We found two microscopic human interaction characteristics from a real-environment face-to-face conversation. The first characteristic is that people quite regularly synchronize their activity level with that of the other participants in a conversation. The second characteristic is that the degree of synchronization increases as the number of participants increases. Based on these microscopic ferromagnetic characteristics, a “conversation activity level” was modeled according to the Ising model. The results of a simulation of activity level based on this model well reproduce macroscopic experimental measurements of activity level. This model will give a new insight into how people interact with each other in a conversation.

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

PubMed

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

2014-05-01

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

Parent-child interactions and objectively measured child physical activity: a cross-sectional study

PubMed Central

2010-01-01

Background Parents influence their children's behaviors directly through specific parenting practices and indirectly through their parenting style. Some practices such as logistical and emotional support have been shown to be positively associated with child physical activity (PA) levels, while for others (e.g. monitoring) the relationship is not clear. The objectives of this study were to determine the relationship between parent's PA-related practices, general parenting style, and children's PA level. Methods During the spring of 2007 a diverse group of 99 parent-child dyads (29% White, 49% Black, 22% Hispanic; 89% mothers) living in low-income rural areas of the US participated in a cross-sectional study. Using validated questionnaires, parents self-reported their parenting style (authoritative, authoritarian, permissive, and uninvolved) and activity-related parenting practices. Height and weight were measured for each dyad and parents reported demographic information. Child PA was measured objectively through accelerometers and expressed as absolute counts and minutes engaged in intensity-specific activity. Results Seventy-six children had valid accelerometer data. Children engaged in 113.4 ± 37.0 min. of moderate-vigorous physical activity (MVPA) per day. Children of permissive parents accumulated more minutes of MVPA than those of uninvolved parents (127.5 vs. 97.1, p < 0.05), while parents who provided above average levels of support had children who participated in more minutes of MVPA (114.2 vs. 98.3, p = 0.03). While controlling for known covariates, an uninvolved parenting style was the only parenting behavior associated with child physical activity. Parenting style moderated the association between two parenting practices - reinforcement and monitoring - and child physical activity. Specifically, post-hoc analyses revealed that for the permissive parenting style group, higher levels of parental reinforcement or monitoring were associated with higher levels of child physical activity. Conclusions This work extends the current literature by demonstrating the potential moderating role of parenting style on the relationship between activity-related parenting practices and children's objectively measured physical activity, while controlling for known covariates. Future studies in this area are warranted and, if confirmed, may help to identify the mechanism by which parents influence their child's physical activity behavior. PMID:20929570

Parent-child interactions and objectively measured child physical activity: a cross-sectional study.

PubMed

Hennessy, Erin; Hughes, Sheryl O; Goldberg, Jeanne P; Hyatt, Raymond R; Economos, Christina D

2010-10-07

Parents influence their children's behaviors directly through specific parenting practices and indirectly through their parenting style. Some practices such as logistical and emotional support have been shown to be positively associated with child physical activity (PA) levels, while for others (e.g. monitoring) the relationship is not clear. The objectives of this study were to determine the relationship between parent's PA-related practices, general parenting style, and children's PA level. During the spring of 2007 a diverse group of 99 parent-child dyads (29% White, 49% Black, 22% Hispanic; 89% mothers) living in low-income rural areas of the US participated in a cross-sectional study. Using validated questionnaires, parents self-reported their parenting style (authoritative, authoritarian, permissive, and uninvolved) and activity-related parenting practices. Height and weight were measured for each dyad and parents reported demographic information. Child PA was measured objectively through accelerometers and expressed as absolute counts and minutes engaged in intensity-specific activity. Seventy-six children had valid accelerometer data. Children engaged in 113.4 ± 37.0 min. of moderate-vigorous physical activity (MVPA) per day. Children of permissive parents accumulated more minutes of MVPA than those of uninvolved parents (127.5 vs. 97.1, p < 0.05), while parents who provided above average levels of support had children who participated in more minutes of MVPA (114.2 vs. 98.3, p = 0.03). While controlling for known covariates, an uninvolved parenting style was the only parenting behavior associated with child physical activity. Parenting style moderated the association between two parenting practices - reinforcement and monitoring - and child physical activity. Specifically, post-hoc analyses revealed that for the permissive parenting style group, higher levels of parental reinforcement or monitoring were associated with higher levels of child physical activity. This work extends the current literature by demonstrating the potential moderating role of parenting style on the relationship between activity-related parenting practices and children's objectively measured physical activity, while controlling for known covariates. Future studies in this area are warranted and, if confirmed, may help to identify the mechanism by which parents influence their child's physical activity behavior.

Evaluation of infrared thermography body temperature and collar-mounted accelerometer and acoustic technology for predicting time of ovulation of cows in a pasture-based system.

PubMed

Talukder, S; Thomson, P C; Kerrisk, K L; Clark, C E F; Celi, P

2015-03-01

This study was conducted to test the hypothesis that the specificity of infrared thermography (IRT) in detecting cows about to ovulate could be improved using different body parts that are less likely to be contaminated by fecal matter. In addition, the combined activity and rumination data captured by accelerometers were evaluated to provide a more accurate indication of ovulation than the activity and rumination data alone. Thermal images of 30 cows were captured for different body areas (eye, ear, muzzle, and vulva) twice daily after AM and PM milking sessions during the entire experimental period. Milk progesterone data and insemination records were used to determine the date of ovulation. Cows were fitted with SCR heat and rumination long-distance tags (SCR HR LD) for 1 month. Activity- and rumination-based estrus alerts were initially identified using default threshold values set by the manufacturer; however, a range of thresholds was also created and tested for both activity and rumination to determine the potential for higher levels of accuracy of ovulation detection. Visual assessment of mounting indicators resulted in 75% sensitivity (Se), 100% specificity (Sp), and 100% positive predictive value (PPV). Overall, IRT showed poor performance for detecting cows about to ovulate. Vulval temperature resulted in the greatest (80%) Sp but the poorest (21%) Se compared with the IRT temperatures of other body areas. The SCR HR LD tags default threshold value resulted in 78% Se, 57% Sp, and 70% PPV. Lowering the activity threshold from the default value improved the sensitivity but created a large number of false positives, which resulted in a decrease in specificity. Lowering the activity threshold to 20 resulted in a detection performance of 80% Se, 94% Sp, and 67% PPV, whereas the rumination levels achieved 35% Se, 69% Sp, and 14% PPV. The area under the curve for the activity level, rumination level, and the combined measures of activity and rumination levels were 0.82, 0.54, and 0.75, respectively. Alerts generated by SCR HR LD tags based on a lower activity threshold level had high sensitivity and may be able to detect a high proportion of cows in ovulatory periods in pasture-based system; however, the specificities and positive predictive value were lower than the visual assessment of mounting indicators. Copyright © 2015 Elsevier Inc. All rights reserved.

Silk gland-specific proteinase inhibitor serpin16 from the Bombyx mori shows cysteine proteinase inhibitory activity.

PubMed

Guo, Peng-Chao; Dong, Zhaoming; Xiao, Li; Li, Tao; Zhang, Yan; He, Huawei; Xia, Qingyou; Zhao, Ping

2015-01-30

Serpins (serine proteinase inhibitors) are widely distributed in different species and are well known for their inhibitory activities towards serine proteinases. Here, we report the functional characterization of Bombyx mori serpin16. Expression analysis showed that serpin16 was specifically expressed at high levels in the silk gland at both the transcriptional and translational levels. Moreover, homology modeling and multi-sequence alignment suggested that serpin16 had a canonical serpin fold, but it contained a unique reactive center loop, which was obviously shorter than that of typical serpins. Inhibitory activity analyses revealed that the target proteinase of serpin18 is a cysteine proteinase, rather than a serine proteinase. Furthermore, a Michaelis complex model of serpin16 with its target proteinase was constructed to explain the structural basis of how serpin16 recognizes the cysteine proteinase and its target specificity. Copyright © 2014 Elsevier Inc. All rights reserved.

The Great Balancing Act. Nutrition Comes Alive. Level 4. Nutrition Educator's Guide and Work Sheets, Information Sheets, Story, Letters to Parents. Revised Edition.

ERIC Educational Resources Information Center

Waldron, Laurie

This guide offers a nutrition education program for students in Kindergarten through Grade 6. Activities span all grades as well as activities for the specific level. Nutrition education objectives are stated for each grade level: (1) grade four--students will explore how to balance food intake and energy output for overall health and physical…

Lens-Specific Gene Recruitment of ζ-Crystallin through Pax6, Nrl-Maf, and Brain Suppressor Sites

PubMed Central

Sharon-Friling, Ronit; Richardson, Jill; Sperbeck, Sally; Lee, Douglas; Rauchman, Michael; Maas, Richard; Swaroop, Anand; Wistow, Graeme

1998-01-01

ζ-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an αCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates ζ-crystallin promoter activity in lens cells. A truncated ζ promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between −498 and −385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens. PMID:9528779

Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1

PubMed Central

Zhu, Yuanqi; Hein, David W.

2007-01-01

Genetic variants of human N-acetyltransferase 1 (NAT1) are associated with cancer and birth defects. N- and O-acetyltransferase catalytic activities, Michaelis-Menten kinetic constants (Km & Vmax), and steady state expression levels of NAT1-specific mRNA and protein were determined for the reference NAT1*4 and variant human NAT1 haplotypes possessing single nucleotide polymorphisms (SNPs) in the open reading frame. Although none of the SNPs caused a significant effect on steady state levels of NAT1-specific mRNA, C97T(R33stop), C190T(R64W), C559T (R187stop) and A752T(D251V) each reduced NAT1 protein level and/or N- and O-acetyltransferase catalytic activities to levels below detection. G560A(R187Q) substantially reduced NAT1 protein level and catalytic activities and increased substrate Km. The G445A(V149I), G459A(synonymous) and T640G(S214A) haplotype present in NAT1*11 significantly (p<0.05) increased NAT1 protein level and catalytic activity. Neither T21G(synonymous), T402C(synonymous), A613G(M205V), T777C(synonymous), G781A(E261K), or A787G(I263V) significantly affected Km, catalytic activity, mRNA or protein level. These results suggest heterogeneity among slow NAT1 acetylator phenotypes. PMID:17909564

Inferring genome-wide functional modulatory network: a case study on NF-κB/RelA transcription factor.

PubMed

Li, Xueling; Zhu, Min; Brasier, Allan R; Kudlicki, Andrzej S

2015-04-01

How different pathways lead to the activation of a specific transcription factor (TF) with specific effects is not fully understood. We model context-specific transcriptional regulation as a modulatory network: triplets composed of a TF, target gene, and modulator. Modulators usually affect the activity of a specific TF at the posttranscriptional level in a target gene-specific action mode. This action may be classified as enhancement, attenuation, or inversion of either activation or inhibition. As a case study, we inferred, from a large collection of expression profiles, all potential modulations of NF-κB/RelA. The predicted modulators include many proteins previously not reported as physically binding to RelA but with relevant functions, such as RNA processing, cell cycle, mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification. Modulators from different processes exert specific prevalent action modes on distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and kinases modulate the NF-κB/RelA activity with specific action modes consistent with their molecular functions and modulation level. The modulatory networks of NF-κB/RelA in the context epithelial-mesenchymal transition (EMT) and burn injury have different modulators, including those involved in extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH, PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury.

Soil Moisture Active Passive (SMAP) Mission Level 4 Carbon (L4_C) Product Specification Document

NASA Technical Reports Server (NTRS)

Glassy, Joe; Kimball, John S.; Jones, Lucas; Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

2015-01-01

This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project.

Antibodies attenuate the capacity of dendritic cells to stimulate HIV-specific cytotoxic T lymphocytes

PubMed Central

Posch, Wilfried; Cardinaud, Sylvain; Hamimi, Chiraz; Fletcher, Adam; Mühlbacher, Annelies; Loacker, Klaus; Eichberger, Paul; Dierich, Manfred P.; Pancino, Gianfranco; Lass-Flörl, Cornelia; Moris, Arnaud; Saez-Cirion, Asier; Wilflingseder, Doris

2014-01-01

Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)–mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. Methods Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8+ T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4+ T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. Results We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8+ T-cell response compared with the earlier described efficient CD8+ T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8+ T-cell clones. Conclusion Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs. PMID:23063584

Hyperthyroidism in Patients with Graves' Ophthalmopathy, and Thyroidal, Skeletal and Eye Muscle Specific Type 2 Deiodinase Enzyme Activities.

PubMed

Molnár, Ildikó; Szentmiklósi, József A; Somogyiné-Vári, Éva

2017-09-01

Graves' ophthalmopathy is characterized by hyperthyroidism, which is associated with higher serum T 3 levels than T 4 due to deiodinase enzymes.The effect of Graves' patient's sera (n=52) with elevated thyroid hormone and TSH receptor or thyroid peroxidase antibody (anti-TPO) levels was investigated on thyroidal, skeletal and eye muscle type 2 deiodinase enzyme (DII) activities. DII activities were measured with 125 I-T 4 substrate, while thyroid hormone and antibody levels with immunoassays.In Graves' ophthalmopathy, sera with elevated FT 4 or FT 3 levels reduced DII activites remarkably in all tissue fractions. Thyroidal DII activities were lower than those using eye muscle fraction (0.6±0.22 vs 1.14±0.43 pmol/mg/min, P<0.006). Effect of sera with increased FT 3 levels demonstrated also reduced DII activities in patients with Graves' ophthalmopathy after methimazole therapy compared to those who had no ophthalmopathy (2.88±2 vs 20.42±11.82 pmol/mg/min, P<0.006 for thyroidal fraction, 4.07±2.72 vs 29.22±15.46 pmol/mg/min, P<0.004 for skeletal muscle, 5.3±3.47 vs 37.87±18.82 pmol/mg/min, P<0.003 for eye muscle). Hyperthyroid sera with TSH receptor antibodies resulted in increased DII activities, while sera with anti-TPO antibodies were connected to lower DII activities in Graves' ophthalmopathy.In summary, the actions of hyperthyroid sera derived from patients with Graves' disease were tested on tissue-specific DII activities. Elevated FT 4 level-induced DII inactivation is present in Graves' ophthalmopathy, which seems to be also present at the beginning of methimazole therapy. Stimulating TSH receptor antibiodies increased DII activities via their nongenomic effects using sera of hyperthyroid Graves' ophthalmopathy, but anti-TPO antibodies could influence DII activities via altering FT 4 levels. © Georg Thieme Verlag KG Stuttgart · New York.

Immunostimulatory effects of collagen from jellyfish in vivo.

PubMed

Morishige, Hitoshi; Sugahara, Takuya; Nishimoto, Sogo; Muranaka, Ayako; Ohno, Fumi; Shiraishi, Ryusuke; Doi, Mikiharu

2011-10-01

We focused on the biological activity of the collagen extracts obtained from the giant edible jellyfish, Nemopilema nomurai. Jellyfish collagen extracts stimulates the production of immunoglobulins (Igs) and cytokines by human hybridoma cells and human peripheral blood lymphocytes. Therefore, we examined the immunoregulatory function of jellyfish collagen extracts in mice. Intake of jellyfish collagen extracts facilitated the Ig production activity of lymphocytes from spleen and Peyer's patch. Furthermore, the levels of Igs in the serum clearly increased after the administration of jellyfish collagen extracts. Intake of bovine collagen from Achilles' tendon also activated lymphocytes activity in mice. The activity of total and antigen-specific Ig production in splenocytes from OVA-challenged mice was also enhanced by collagen intake. However, the total and OVA-specific IgE levels in the serum were not affected by the collagen intake. These results suggested that jellyfish collagen extracts stimulates an immune response in vivo, without inducing allergic complications.

Cancer incidence attributable to inadequate physical activity in Alberta in 2012

PubMed Central

Brenner, Darren R.; Poirier, Abbey E.; Grundy, Anne; Khandwala, Farah; McFadden, Alison; Friedenreich, Christine M.

2017-01-01

Background: Physical inactivity has been consistently associated with increased risk of colorectal, endometrial, breast (in postmenopausal women), prostate, lung and ovarian cancers. The objective of the current analysis was to estimate the proportion and absolute number of site-specific cancer cases attributable to inadequate physical activity in Alberta in 2012. Methods: We used population attributable risks to estimate the proportion of each site-specific cancer attributable to inactivity. Relative risk estimates were obtained from the epidemiological literature, and prevalence estimates were calculated with the use of data from the Canadian Community Health Survey cycle 2.1 (2003). Respondents who acquired 1.5-2.9 kcal/kg per day and less than 1.5 kcal/kg per day of physical activity were classified as moderately active and inactive, respectively, and both levels were considered inadequate for mitigating cancer risks. We obtained age-, sex- and site-specific cancer incidence data from the Alberta Cancer Registry for 2012. Results: About 59%-75% of men and 69%-78% of women did not engage in adequate physical activity. Overall, 13.8% of cancers across all associated cancers were estimated to be attributable to inadequate physical activity, representing 7.2% of all cancers diagnosed in Alberta in 2012. Suboptimal levels of physical activity had a greater impact among women: the proportion of all associated cancers attributable to inadequate physical activity was 18.3% for women and 9.9% for men. Interpretation: A substantial proportion of cancer cases diagnosed in Alberta were estimated to be attributable to inadequate physical activity. With the high prevalence of physical inactivity among adults in the province, developing strategies to increase physical activity levels could have a notable impact on reducing future cancer burden in Alberta. PMID:28468830

Exploring the relationship between outdoor recreation activities, community participation, and environmental attitudes

Treesearch

Lindsey Barker; Chad Dawson

2012-01-01

The relationship between environmental attitudes (EA) and environmentally responsible behavior (ERB) has been the focus of several studies in environmental psychology and recreation research. The purpose of this study was to explore the relationship between EAs and ERBs at both a general level and at an activity-specific level using a 2009 survey of motorized...

Achievement-Based Rewards and Intrinsic Motivation: A Test of Cognitive Mediators

ERIC Educational Resources Information Center

Cameron, Judy; Pierce, W. David; Banko, Katherine M.; Gear, Amber

2005-01-01

This study assessed how rewards impacted intrinsic motivation when students were rewarded for achievement while learning an activity, for performing at a specific level on a test, or for both. Undergraduate university students engaged in a problem-solving activity. The design was a 2 * 2 factorial with 2 levels of reward in a learning phase…

Increased choline kinase activity in 1,2-dimethylhydrazine-induced rat colon cancer.

PubMed

Nakagami, K; Uchida, T; Ohwada, S; Koibuchi, Y; Morishita, Y

1999-11-01

Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase alpha protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase alpha gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation.

Seasonal, tissue-specific regulation of Akt/protein kinase B and glycogen synthase in hibernators.

PubMed

Hoehn, Kyle L; Hudachek, Susan F; Summers, Scott A; Florant, Gregory L

2004-03-01

Yellow-bellied marmots (Marmota flaviventris) exhibit a circannual cycle of hyperphagia and nutrient storage in the summer followed by hibernation in the winter. This annual cycle of body mass gain and loss is primarily due to large-scale accumulation of lipid in the summer, which is then mobilized and oxidized for energy during winter. The rapid and predictable change in body mass makes these animals ideal for studies investigating the molecular basis for body weight regulation. In the study described herein, we monitored seasonal changes in the protein levels and activity of a central regulator of anabolic metabolism, the serine-threonine kinase Akt-protein kinase B (Akt/PKB), during the months accompanying maximal weight gain and entry into hibernation (June-November). Interestingly, under fasting conditions, Akt/PKB demonstrated a tissue-specific seasonal activation. Specifically, although Akt/PKB levels did not change, the activity of Akt/PKB (isoforms 1/alpha and 2/beta) in white adipose tissue (WAT) increased significantly in July. Moreover, glycogen synthase, which lies downstream of Akt/PKB on a linear pathway linking the enzyme to the stimulation of glycogen synthesis, demonstrated a similar pattern of seasonal activation. By contrast, Akt/PKB activity in skeletal muscle peaked much later (i.e., September). These data suggest the existence of a novel, tissue-specific mechanism regulating Akt/PKB activation during periods of marked anabolism.

Does outpatient physical therapy with the aim of improving health-related physical fitness influence the level of physical activity in patients with long-term musculoskeletal conditions?

PubMed

Holm, I; Tveter, A T; Moseng, T; Dagfinrud, H

2015-09-01

To evaluate any change in self-reported level of physical activity in patients receiving a general physical exercise programme in addition to disease-specific physiotherapy treatment. Pre-post-intervention study. Outpatient physiotherapy clinics. One hundred and ninety patients with long-term musculoskeletal conditions attending outpatient physiotherapy were recruited from seven physiotherapy clinics. Physiotherapy including disease-specific modalities and a general individually tailored exercise programme. Patients were evaluated at baseline and at the end of the programme. International Physical Activity Questionnaire short form (IPAQ-sf) and COOP WONCA functional assessment charts. Forty-two patients were excluded from the analysis because they did not complete the IPAQ-sf correctly or dropped out during the treatment period. There was a significant increase in the number of metabolic equivalent task (MET)-min/week for vigorous and moderate-intensity activities, walking and total physical activity. The number of exercise sessions per week increased from 1.8 [standard deviation (SD) 0.9] to 2.2 (SD 1.2) (P=0.001). The proportion of patients with a low level of physical activity decreased by 12%, and the proportion of the participants who did not/could not exercise decreased from 26% to 8%. The COOP WONCA charts showed significant improvements in the physical fitness, feelings, daily activities and social activities items. A significant increase was found in the number of MET-min/week for all activity levels. Therefore, a general physical exercise programme initiated by a physiotherapist led to a positive change in level of physical activity. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

[Summary insulin-like activity of the blood serum in breast cancer and in specific age-related pathology].

PubMed

Kovaleva, I G; Ostroumova, M N; Tsyrlina, E V; Bobrov, Iu F; Evtushenko, T V

1982-01-01

Total insulin-like activity (ILA) was evaluated by biological testing blood serum on the basis of stimulation of glycogen synthesis in rat diaphragm in vivo. Glucose loading was followed by an increase in ILA and radioimmune insulin (RII) levels both in patients with breast fibroadenomatosis and healthy controls. However, the patients revealed an increased RII response matched by absence of ILA response, while the basal ILA was three times that in healthy controls. An elevated basal level of ILA was also observed in patients with coronary atherosclerosis and mental depression. Enhanced hyperinsulinism due to RII complementary factors, capable of insulin-like activity, may prove to be a factor in specific age-associated pathology (cancer, atherosclerosis, mental depression).

Association of daily physical activity level with health-related factors by gender and age-specific differences among Korean adults based on the sixth (2014-2015) Korea national health and nutrition examination survey

PubMed

Chung, Nana; Park, Hun-Young; Park, Mi-Young; Hwang, Yoon-Young; Lee, Chi-Ho; Han, Jin-Soo; So, Jaemoo; Kim, Jisu; Park, Jonghoon; Lim, Kiwon

2017-06-30

This study examined the effects of daily physical activity level on health-related factors according to gender and identified age-specific differences among Korean adults. Using data from the Korea National Health and Nutrition Examination Survey VI (2014-2015), we selected adults aged 19-64 years who participated in both a health examination and health interview survey. The study included 6,457 participants 19-64 years of age (2,611 men, 3,846 women). Assessment of the differences in health-related factors according to age and physical activity in men and women by repeated two-way analysis of variance (ANOVA) revealed significant interaction effects on total cholesterol (TC) and triglyceride (TG) levels and diastolic blood pressure (DBP) in male participants, but there were no significant interaction effects for any health-related factors in female participants. The group of female participants aged 40-64 years with daily physical activity levels over 200 kcal showed a significantly increased prevalence of 46% for dyslipidemia compared to that in female participants with daily physical activity levels below 200 kcal. Physical activity was positively correlated with weight and high-density lipoprotein cholesterol (HDL-C) levels in men 19-39 years of age, compared to weight, waist circumference (WC), body mass index (BMI), and DBP in men 40-64 years of age, and weight, WC, BMI, glycated hemoglobin (HbA1c) and triglyceride (TG) levels in women 19-39 years of age. In women 40- 64 years of age, physical activity was especially significantly positively correlated with weight, BMI, HDL-C and negatively correlated with fasting glucose and TG levels. In male and female participants, the 40-64-year age group showed negative results for health-related factors compared to those in the 19-39-year age group. The higher the weight, WC, BMI, the higher is the physical activity level. Physical activity levels were significantly positively correlated with health-related variables. ©2017 The Korean Society for Exercise Nutrition

Association of daily physical activity level with health-related factors by gender and age-specific differences among Korean adults based on the sixth (2014-2015) Korea national health and nutrition examination survey

PubMed Central

Chung, Nana; Park, Hun-Young; Park, Mi-Young; Hwang, Yoon-Young; Lee, Chi-Ho; Han, Jin-Soo; So, Jaemoo; Kim, Jisu; Park, Jonghoon; Lim, Kiwon

2017-01-01

[Purpose] This study examined the effects of daily physical activity level on health-related factors according to gender and identified age-specific differences among Korean adults. [Methods] Using data from the Korea National Health and Nutrition Examination Survey VI (2014-2015), we selected adults aged 19-64 years who participated in both a health examination and health interview survey. The study included 6,457 participants 19-64 years of age (2,611 men, 3,846 women). [Results] Assessment of the differences in health-related factors according to age and physical activity in men and women by repeated two-way analysis of variance (ANOVA) revealed significant interaction effects on total cholesterol (TC) and triglyceride (TG) levels and diastolic blood pressure (DBP) in male participants, but there were no significant interaction effects for any health-related factors in female participants. The group of female participants aged 40-64 years with daily physical activity levels over 200 kcal showed a significantly increased prevalence of 46% for dyslipidemia compared to that in female participants with daily physical activity levels below 200 kcal. Physical activity was positively correlated with weight and high-density lipoprotein cholesterol (HDL-C) levels in men 19-39 years of age, compared to weight, waist circumference (WC), body mass index (BMI), and DBP in men 40-64 years of age, and weight, WC, BMI, glycated hemoglobin (HbA1c) and triglyceride (TG) levels in women 19-39 years of age. In women 40- 64 years of age, physical activity was especially significantly positively correlated with weight, BMI, HDL-C and negatively correlated with fasting glucose and TG levels. [Conclusion] In male and female participants, the 40-64-year age group showed negative results for health-related factors compared to those in the 19-39-year age group. The higher the weight, WC, BMI, the higher is the physical activity level. Physical activity levels were significantly positively correlated with health-related variables. PMID:28715884

Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis

PubMed Central

Son, Aran; Kim, Min Seuk; Jo, Hae; Byun, Hae Mi

2012-01-01

The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca2+ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP3) and IP3-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP3 and evaluated IP3-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca2+ signaling proteins such as IP3 receptors (IP3Rs), plasma membrane Ca2+ ATPase, and sarco/endoplasmic reticulum Ca2+ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP3 was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP3 levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP3Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP3Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP3 levels and the IP3-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis. PMID:22416217

Friendship networks and physical activity and sedentary behavior among youth: a systematized review.

PubMed

Sawka, Keri Jo; McCormack, Gavin R; Nettel-Aguirre, Alberto; Hawe, Penelope; Doyle-Baker, Patricia K

2013-12-01

Low levels of physical activity and increased participation in sedentary leisure-time activities are two important obesity-risk behaviors that impact the health of today's youth. Friend's health behaviors have been shown to influence individual health behaviors; however, current evidence on the specific role of friendship networks in relation to levels of physical activity and sedentary behavior is limited. The purpose of this review was to summarize evidence on friendship networks and both physical activity and sedentary behavior among children and adolescents. After a search of seven scientific databases and reference scans, a total of thirteen articles were eligible for inclusion. All assessed the association between friendship networks and physical activity, while three also assessed sedentary behavior. Overall, higher levels of physical activity among friends are associated with higher levels of physical activity of the individual. Longitudinal studies reveal that an individual's level of physical activity changes to reflect his/her friends' higher level of physical activity. Boys tend to be influenced by their friendship network to a greater extent than girls. There is mixed evidence surrounding a friend's sedentary behavior and individual sedentary behavior. Friends' physical activity level appears to have a significant influence on individual's physical activity level. Evidence surrounding sedentary behavior is limited and mixed. Results from this review could inform effective public health interventions that harness the influence of friends to increase physical activity levels among children and adolescents.

The early cellular signatures of protective immunity induced by live viral vaccination.

PubMed

Kohler, Siegfried; Bethke, Nicole; Böthe, Matthias; Sommerick, Sophie; Frentsch, Marco; Romagnani, Chiara; Niedrig, Matthias; Thiel, Andreas

2012-09-01

Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T- and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4(+) T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-β from degradation and induce apoptosis in prostate cancer cells.

PubMed

Singh, Vishal; Sharma, Vikas; Verma, Vikas; Pandey, Deepti; Yadav, Santosh K; Maikhuri, Jagdamba P; Gupta, Gopal

2015-12-01

To investigate apigenin (5,7,4-trihydroxyflavone), a dietary flavonoid with proteasome-inhibitory activity (desired for the management of multiple types of cancers), against FDA-approved anticancer proteasome inhibitor bortezomib in context to its effects on the tumor suppressor estrogen receptor-beta (ER-β) in prostate cancer cells. Prostate cancer (PC-3) cells were treated with either apigenin or bortezomib, and proliferation inhibition was correlated with proteasomal biochemistry, ER-degradation and cell apoptosis. Apigenin specifically inhibited only chymotrypsin-like activity of proteasome without affecting trypsin and caspase-like activities, which was in contrast to the non-specific inhibition of all the three activities by bortezomib. Apigenin selectively increased the protein levels of ER-β at 1.8 and 10.0 µM (without affecting mRNA levels) and preferentially accumulated ubiquitinated ER-β over ER-α in PC-3. Apigenin-treated cells exhibited increased ER-β interactions with ubiquitin-protein ligase E6AP, downregulated PSMA5 (α-5 subunit for assembly of 20S proteasome) without affecting PSMB1 (β-1 subunit), PSMB2 (β-2 subunit) and PSMB5 (β-5 subunit, whose overexpression by bortezomib causes drug resistance) of proteasome at mRNA levels. Caspase-3 activation in PC-3 by apigenin was dependent on caspase-8 activity but independent of mitochondrial membrane depolarization. The deubiquitinase USP14 activity, which antagonizes degradation of proteins via proteasome, was significantly increased by apigenin treatment. Apigenin selectively inhibits proteasomal degradation of tumor suppressor ER-β by specifically inhibiting chymotrypsin-like activity of proteasome, preventing its assembly via PSMA5 and inhibiting USP14 enzyme activity in prostate cancer cells, resulting in cancer cell apoptosis. Unlike bortezomib, apigenin's actions are subtle, precise, mechanistically distinct and capable of abstaining drug resistance.

Where they live, how they play: Neighborhood greenness and outdoor physical activity among preschoolers

PubMed Central

2011-01-01

Background Emerging empirical evidence suggests exposure to "green" environments may encourage higher levels of physical activity among children. Few studies, however, have explored this association exclusively in pre-school aged children in the United States. We examined whether residing in neighborhoods with higher levels of greenness was associated with higher levels of outdoor physical activity among preschoolers. In addition, we also explored whether outdoor playing behaviors (e.g., active vs. quiet) were influenced by levels of neighborhood greenness independent of demographic and parental support factors. Results Higher levels of neighborhood greenness as measured by the Normalized Difference Vegetation Index (NDVI) was associated with higher levels of outdoor playing time among preschool-aged children in our sample. Specifically, a one unit increase in neighborhood greenness increased a child's outdoor playing time by approximately 3 minutes. A dose-response relationship was observed between increasing levels of parental support for physical activity (e.g., time spent playing with children) and child outdoor physical activity (p < 0.01). Conclusions Consistent with previous studies, neighborhood greenness influences physical activity behavior. However, for preschoolers, parental involvement may be more critical for improving physical activity levels. PMID:22165919

Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration.

PubMed

Creus-Muncunill, Jordi; Rué, Laura; Alcalá-Vida, Rafael; Badillos-Rodríguez, Raquel; Romaní-Aumedes, Joan; Marco, Sonia; Alberch, Jordi; Perez-Otaño, Isabel; Malagelada, Cristina; Pérez-Navarro, Esther

2018-02-19

Rictor associates with mTOR to form the mTORC2 complex, which activity regulates neuronal function and survival. Neurodegenerative diseases are characterized by the presence of neuronal dysfunction and cell death in specific brain regions such as for example Huntington's disease (HD), which is characterized by the loss of striatal projection neurons leading to motor dysfunction. Although HD is caused by the expression of mutant huntingtin, cell death occurs gradually suggesting that neurons have the capability to activate compensatory mechanisms to deal with neuronal dysfunction and later cell death. Here, we analyzed whether mTORC2 activity could be altered by the presence of mutant huntingtin. We observed that Rictor levels are specifically increased in the striatum of HD mouse models and in the putamen of HD patients. Rictor-mTOR interaction and the phosphorylation levels of Akt, one of the targets of the mTORC2 complex, were increased in the striatum of the R6/1 mouse model of HD suggesting increased mTORC2 signaling. Interestingly, acute downregulation of Rictor in striatal cells in vitro reduced mTORC2 activity, as shown by reduced levels of phospho-Akt, and increased mutant huntingtin-induced cell death. Accordingly, overexpression of Rictor increased mTORC2 activity counteracting cell death. Furthermore, normalization of endogenous Rictor levels in the striatum of R6/1 mouse worsened motor symptoms suggesting an induction of neuronal dysfunction. In conclusion, our results suggest that increased Rictor striatal levels could counteract neuronal dysfunction induced by mutant huntingtin.

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.

Active video games and physical activity recommendations: a comparison of the Gamercize Stepper, XBOX Kinect and XaviX J-Mat.

PubMed

Mellecker, R R; McManus, A M

2014-05-01

The current study was designed to evaluate the intensity levels of three exergames and determine the association with physical activity recommendations that correspond to specific outcomes. The variation in cardiovascular responses between the three exergames was also examined. We employed a cross-sectional laboratory design. We recruited 18 girls to participate in a peak VO2 test and to play Gamercize, Kinect River Rush, XaviX J-Mat at three separate exergaming sessions. Linear regression equations of heart rate and percentage of peak VO2 were calculated for each participant to determine the intensity of exergame play. Differences in intensity between the three exergames and time spent in the recommended moderate (heart rate at ≥ 55% peak VO2) and vigorous (heart rate at ≥ 75% peak VO2) intensity levels were analyzed. We calculated the coefficient of variation for the mean heart rate to determine the difference in variance in heart rate values for the three exergames. When playing Gamercize and Kinect the girls did not play at recommended moderate or vigorous levels. Although the girls did not play at vigorous levels when playing XaviX J-Mat, our results showed that when playing XaviX J-Mat they did play at moderate intensity levels. No significant differences in the coefficient of variation between the three exergames were apparent. If active gaming is to be used to increase physical activity levels then individual differences in levels of exertion and specific activity recommendations need to be taken into consideration. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

PubMed

Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

Measuring Assurance of Learning at the Degree Program and Academic Major Levels

ERIC Educational Resources Information Center

Marshall, Leisa Lynn

2007-01-01

In this article, the author examines the validity of performing assurance of learning (AOL) activities at the degree program level (e.g., bachelor's level) and the major level (e.g., accounting, finance). She examines 3 learning goals: management-specific knowledge, problem solving, and communication. The results strongly suggest that the AOL…

Is subscapularis recruited in a similar manner during shoulder internal rotation exercises and belly press and lift off tests?

PubMed

Ginn, Karen A; Reed, Darren; Jones, Chelsea; Downes, Anthony; Cathers, Ian; Halaki, Mark

2017-06-01

Although the belly press and lift off tests are recommended to assess subscapularis function, shoulder internal rotation (IR) exercises performed in other shoulder positions are more commonly used to restore subscapularis function. It is not known if shoulder IR exercises specifically activate subscapularis to the same degree as the lift off and belly press tests, and thus have the potential to effect subscapularis strength gains. Therefore, the aim was to compare subscapularis activation levels with those of other shoulder internal rotator muscles during the belly press and lift off tests and shoulder IR exercise positions. Original research. Twenty asymptomatic volunteers performed maximal isometric contractions during the belly press and lift off tests and shoulder IR performed at 90° and 0° abduction in an upright position and supported at 90° abduction in supine. Muscle activation levels were recorded using a combination of indwelling and surface electrodes. Data were normalized to maximum voluntary contractions and averaged. Moderate average subscapularis activation levels were recorded during all shoulder IR tasks examined with no significant difference between tasks (p=0.18). The belly press test was the only IR task in which subscapularis activation levels were significantly higher than all other shoulder internal rotator muscles (p<0.05). Shoulder IR exercises activate subscapularis to similar moderate levels as the belly press and lift off tests and therefore, have similar potential to strengthen subscapularis. However, the belly press test, with significantly higher subscapularis activation than other shoulder internal rotators, more specifically targets subscapularis. Copyright © 2016. Published by Elsevier Ltd.

Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial

PubMed Central

Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo

2012-01-01

Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240

A chromatin activity based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing

PubMed Central

Liu, Cui; Yu, Yanbao; Liu, Feng; Wei, Xin; Wrobel, John A.; Gunawardena, Harsha P.; Zhou, Li; Jin, Jian; Chen, Xian

2015-01-01

Immune cells develop endotoxin tolerance (ET) after prolonged stimulation. ET increases the level of a repression mark H3K9me2 in the transcriptional-silent chromatin specifically associated with pro-inflammatory genes. However, it is not clear what proteins are functionally involved in this process. Here we show that a novel chromatin activity based chemoproteomic (ChaC) approach can dissect the functional chromatin protein complexes that regulate ET-associated inflammation. Using UNC0638 that binds the enzymatically active H3K9-specific methyltransferase G9a/GLP, ChaC reveals that G9a is constitutively active at a G9a-dependent mega-dalton repressome in primary endotoxin-tolerant macrophages. G9a/GLP broadly impacts the ET-specific reprogramming of the histone code landscape, chromatin remodeling, and the activities of select transcription factors. We discover that the G9a-dependent epigenetic environment promotes the transcriptional repression activity of c-Myc for gene-specific co-regulation of chronic inflammation. ChaC may be also applicable to dissect other functional protein complexes in the context of phenotypic chromatin architectures. PMID:25502336

Contributions of non-occupational activities to total noise exposure of construction workers.

PubMed

Neitzel, Richard; Seixas, Noah; Goldman, Bryan; Daniell, William

2004-07-01

This paper describes how exposures received during routine and episodic non-occupational activities contribute to total noise exposure in a group of occupationally exposed workers. Two-hundred and sixty-six construction apprentices enrolled in a longitudinal hearing loss study and completed questionnaires at 1 yr of follow-up to determine their episodic activities (e.g. concert attendance, power tool use, firearms exposure). Noise exposure levels for these episodic exposures were determined from the published literature. Routine activities were assessed using activity cards filled out over 530 subject-days, along with noise dosimetry measurements made over 124 subject-days of measurement. Equivalent Leq exposure levels were then calculated for specific activities. These activity-specific Leq values were combined into estimated individual annual Leq exposure levels for the 6760 nominal annual non-occupational hours in a year (LAeq6760h), which were then transformed into equivalent levels for a 2000 h exposure period (LA2000hn) for comparison with occupational noise exposure risk criteria. The mean non-occupational LAeq6760h exposure values for the cohort ranged from 56 to 87 dBA (equivalent LA2000hn 62-93 dBA). At the mid range of the routine and episodic activity exposure level distribution, the mean LAeq6760h was 73 dBA (LA2000hn 78 dBA). Nineteen percent of the LA2000hn non-occupational exposures exceeded 85 dBA, the generally recommended occupational limit for a 2000 h workyear, at the mid-range of exposure levels. Due to a lack of available data, firearms use could not be incorporated into the total noise exposure estimates. However, firearms users reported more exposure to other noisy non-occupational activities and had statistically significantly higher estimated exposure levels even without including their firearms exposure than did non-shooters. When compared with the high levels of occupational noise found in construction, non-occupational noise exposures generally present little additional exposure for most workers. However, they may contribute significantly to overall exposure in the subset of workers who frequently participate in selected noisy activities.

MiRAR-miRNA Activity Reporter for Living Cells.

PubMed

Turk, Matthew A; Chung, Christina Z; Manni, Emad; Zukowski, Stephanie A; Engineer, Anish; Badakhshi, Yasaman; Bi, Yumin; Heinemann, Ilka U

2018-06-19

microRNA (miRNA) activity and regulation are of increasing interest as new therapeutic targets. Traditional approaches to assess miRNA levels in cells rely on RNA sequencing or quantitative PCR. While useful, these approaches are based on RNA extraction and cannot be applied in real-time to observe miRNA activity with single-cell resolution. We developed a green fluorescence protein (GFP)-based reporter system that allows for a direct, real-time readout of changes in miRNA activity in live cells. The miRNA activity reporter (MiRAR) consists of GFP fused to a 3′ untranslated region containing specific miRNA binding sites, resulting in miRNA activity-dependent GFP expression. Using qPCR, we verified the inverse relationship of GFP fluorescence and miRNA levels. We demonstrated that this novel optogenetic reporter system quantifies cellular levels of the tumor suppressor miRNA let-7 in real-time in single Human embryonic kidney 293 (HEK 293) cells. Our data shows that the MiRAR can be applied to detect changes in miRNA levels upon disruption of miRNA degradation pathways. We further show that the reporter could be adapted to monitor another disease-relevant miRNA, miR-122. With trivial modifications, this approach could be applied across the miRNome for quantification of many specific miRNA in cell cultures, tissues, or transgenic animal models.

Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells

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

Long, Cong; Wang, Jingchao; Guo, Wei

Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated thatmore » triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells. - Highlights: • Triptolide reduces expression of hTERT by decreasing its transcription level. • Triptolide reduces promoter activity and stability of hTERT. • Triptolide down-regulates expression of Sp1. • Special Sp1 shRNAs inhibit transcription and protein expression of hTERT. • Triptolide and Sp1 shRNA2 induce cell proliferation inhibition and apoptosis.« less

Best Practices and Recommendations for Increasing Physical Activity in Youth

ERIC Educational Resources Information Center

Erwin, Heather; Beets, Michael W.; Centeio, Erin; Morrow, James R., Jr.

2014-01-01

Many efforts to increase the physical activity levels of Americans have been introduced and implemented over the past 20 years. National Physical Activity Guidelines have been established, and the National Physical Activity Plan (NPAP) is now in place, which includes a specific sector dedicated to education. This article addresses the Education…

The self as a mediator between personality and adjustment.

PubMed

Graziano, W G; Jensen-Campbell, L A; Finch, J F

1997-08-01

The self can be conceptualized as a mediating agent that translates personality into situated goal-directed activities and adaptation. This research used a level-of-analysis approach to link personality dimensions (Level I) to self-systems (Level II) and to teacher ratings of adjustment in African American, Mexican American, and European American students (N = 317). The authors hypothesized that links among aspects of self-esteem and teacher ratings of adjustment would be domain specific, and those links to dimensions of the 5-factor model would reflects the domain specificity. Structural equation modeling corroborated hypotheses about domain specificity in links between adjustment and 5-factor dimensions. Results were discussed in terms of levels of analysis for personality structure, personality development, and age-related adaptations to social contexts.

It is time to combine the two main traditions in the research on the neural correlates of consciousness: C = L × D

PubMed Central

Bachmann, Talis; Hudetz, Anthony G.

2014-01-01

Research on neural correlates of consciousness has been conducted and carried out mostly from within two relatively autonomous paradigmatic traditions – studying the specific contents of conscious experience and their brain-process correlates and studying the level of consciousness. In the present paper we offer a theoretical integration suggesting that an emphasis has to be put on understanding the mechanisms of consciousness (and not a mere correlates) and in doing this, the two paradigmatic traditions must be combined. We argue that consciousness emerges as a result of interaction of brain mechanisms specialized for representing the specific contents of perception/cognition – the data – and mechanisms specialized for regulating the level of activity of whatever data the content-carrying specific mechanisms happen to represent. Each of these mechanisms are necessary because without the contents there is no conscious experience and without the required level of activity the processed contents remain unconscious. Together the two mechanisms, when activated up to a necessary degree each, provide conditions sufficient for conscious experience to emerge. This proposal is related to pertinent experimental evidence. PMID:25202297

Differential Neural Activity during Search of Specific and General Autobiographical Memories Elicited by Musical Cues

ERIC Educational Resources Information Center

Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S.

2011-01-01

Previous neuroimaging studies that have examined autobiographical memory specificity have utilized retrieval cues associated with prior searches of the event, potentially changing the retrieval processes being investigated. In the current study, musical cues were used to naturally elicit memories from multiple levels of specificity (i.e., lifetime…

Groundwater quality of the Gulf Coast aquifer system, Houston, Texas, 2010

USGS Publications Warehouse

Oden, Jeannette H.; Brown, Dexter W.; Oden, Timothy D.

2011-01-01

Gross alpha-particle activities and beta-particle activities for all 47 samples were analyzed at 72 hours after sample collection and again at 30 days after sample collection, allowing for the measurement of the activity of short-lived isotopes. Gross alpha-particle activities reported in this report were not adjusted for activity contributions by radon or uranium and, therefore, are conservatively high estimates if compared to the U.S. Environmental Protection Agency National Primary Drinking Water Regulation for adjusted gross alpha-particle activity. The gross alpha-particle activities at 30 days in the samples ranged from R0.60 to 25.5 picocuries per liter and at 72 hours ranged from 2.58 to 39.7 picocuries per liter, and the "R" preceding the value of 0.60 picocuries per liter refers to a nondetected result less than the sample-specific critical level. Gross beta-particle activities measured at 30 days ranged from 1.17 to 14.4 picocuries per liter and at 72 hours ranged from 1.97 to 4.4 picocuries per liter. Filtered uranium was detected in quantifiable amounts in all of the 47 wells sampled. The uranium concentrations ranged from 0.03 to 42.7 micrograms per liter. One sample was analyzed for carbon-14, and the amount of modern atmospheric carbon was reported as 0.2 percent. Six source-water samples collected from municipal supply wells were analyzed for radium-226, and all of the concentrations were considered detectable concentrations (greater than their associated sample-specific critical level). Three source-water samples collected were analyzed for radon-222, and all of the concentrations were substantially greater than the associated sample-specific critical level.

Finding the music of speech: Musical knowledge influences pitch processing in speech.

PubMed

Vanden Bosch der Nederlanden, Christina M; Hannon, Erin E; Snyder, Joel S

2015-10-01

Few studies comparing music and language processing have adequately controlled for low-level acoustical differences, making it unclear whether differences in music and language processing arise from domain-specific knowledge, acoustic characteristics, or both. We controlled acoustic characteristics by using the speech-to-song illusion, which often results in a perceptual transformation to song after several repetitions of an utterance. Participants performed a same-different pitch discrimination task for the initial repetition (heard as speech) and the final repetition (heard as song). Better detection was observed for pitch changes that violated rather than conformed to Western musical scale structure, but only when utterances transformed to song, indicating that music-specific pitch representations were activated and influenced perception. This shows that music-specific processes can be activated when an utterance is heard as song, suggesting that the high-level status of a stimulus as either language or music can be behaviorally dissociated from low-level acoustic factors. Copyright © 2015 Elsevier B.V. All rights reserved.

Verification of Ceramic Structures

NASA Astrophysics Data System (ADS)

Behar-Lafenetre, Stephanie; Cornillon, Laurence; Rancurel, Michael; De Graaf, Dennis; Hartmann, Peter; Coe, Graham; Laine, Benoit

2012-07-01

In the framework of the “Mechanical Design and Verification Methodologies for Ceramic Structures” contract [1] awarded by ESA, Thales Alenia Space has investigated literature and practices in affiliated industries to propose a methodological guideline for verification of ceramic spacecraft and instrument structures. It has been written in order to be applicable to most types of ceramic or glass-ceramic materials - typically Cesic®, HBCesic®, Silicon Nitride, Silicon Carbide and ZERODUR®. The proposed guideline describes the activities to be performed at material level in order to cover all the specific aspects of ceramics (Weibull distribution, brittle behaviour, sub-critical crack growth). Elementary tests and their post-processing methods are described, and recommendations for optimization of the test plan are given in order to have a consistent database. The application of this method is shown on an example in a dedicated article [7]. Then the verification activities to be performed at system level are described. This includes classical verification activities based on relevant standard (ECSS Verification [4]), plus specific analytical, testing and inspection features. The analysis methodology takes into account the specific behaviour of ceramic materials, especially the statistical distribution of failures (Weibull) and the method to transfer it from elementary data to a full-scale structure. The demonstration of the efficiency of this method is described in a dedicated article [8]. The verification is completed by classical full-scale testing activities. Indications about proof testing, case of use and implementation are given and specific inspection and protection measures are described. These additional activities are necessary to ensure the required reliability. The aim of the guideline is to describe how to reach the same reliability level as for structures made of more classical materials (metals, composites).

Gastrin-releasing peptide receptor-induced internalization, down-regulation, desensitization, and growth: possible role for cyclic AMP.

PubMed

Benya, R V; Fathi, Z; Kusui, T; Pradhan, T; Battey, J F; Jensen, R T

1994-08-01

Stimulation of the gastrin-releasing peptide receptor (GRP-R) in Swiss 3T3 cells resembles that of a number of other recently described G protein-coupled receptors, insofar as both the phospholipase C and adenylyl cyclase signal transduction pathways are activated. GRP-R activation induces numerous alterations in both the cell and the receptor, but because two signal transduction pathways are activated it is difficult to determine the specific contributions of either pathway. We have found that BALB/3T3 fibroblasts transfected with the coding sequence for the GRP-R are pharmacologically indistinguishable from native receptor-expressing cells and activate phospholipase C in a manner similar to that of the native receptor but fail to increase cAMP in response to bombesin; thus, they may be useful cells to explore the role of activation of each pathway in altering cell and receptor function. Swiss 3T3 cells and GRP-R-transfected BALB/3T3 cells expressed identically glycosylated receptors that bound various agonists and antagonists similarly. G protein activation, as determined by evaluation of agonist-induced activation of phospholipase C and by analysis of the effect of guanosine-5'-(beta,gamma-imido)triphosphate on GRP-R binding affinity, was indistinguishable. Agonist stimulation of GRP-R caused similar receptor changes (internalization and down-regulation) and homologous desensitization in both cell types. Bombesin stimulation of Swiss 3T3 cells that had been preincubated with forskolin increased cAMP levels 9-fold, but no bombesin-specific increase in cAMP levels was detected in transfected cells, even though forskolin and cholera toxin increased cAMP levels in these cells. Quiescent Swiss 3T3 cells treated with bombesin rapidly increased c-fos mRNA levels and [3H]thymidine incorporation, whereas both effects were potentiated by forskolin. The specific protein kinase A inhibitor H-89 blocked increases in c-fos levels and [3H]thymidine incorporation induced by low concentrations of bombesin. GRP-R-transfected BALB/3T3 cells increased c-fos mRNA levels and [3H]thymidine incorporation with the addition of serum but not bombesin. These data suggest that bombesin-stimulated increases in cellular levels of cAMP appear not to be an important mediator of GRP-R internalization, down-regulation, or desensitization but do play an important role in bombesin-induced mitogenesis.

Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

PubMed

Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

2013-01-01

One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT.

Friendship networks and physical activity and sedentary behavior among youth: a systematized review

PubMed Central

2013-01-01

Background Low levels of physical activity and increased participation in sedentary leisure-time activities are two important obesity-risk behaviors that impact the health of today’s youth. Friend’s health behaviors have been shown to influence individual health behaviors; however, current evidence on the specific role of friendship networks in relation to levels of physical activity and sedentary behavior is limited. The purpose of this review was to summarize evidence on friendship networks and both physical activity and sedentary behavior among children and adolescents. Method After a search of seven scientific databases and reference scans, a total of thirteen articles were eligible for inclusion. All assessed the association between friendship networks and physical activity, while three also assessed sedentary behavior. Results Overall, higher levels of physical activity among friends are associated with higher levels of physical activity of the individual. Longitudinal studies reveal that an individual’s level of physical activity changes to reflect his/her friends’ higher level of physical activity. Boys tend to be influenced by their friendship network to a greater extent than girls. There is mixed evidence surrounding a friend’s sedentary behavior and individual sedentary behavior. Conclusion Friends’ physical activity level appears to have a significant influence on individual’s physical activity level. Evidence surrounding sedentary behavior is limited and mixed. Results from this review could inform effective public health interventions that harness the influence of friends to increase physical activity levels among children and adolescents. PMID:24289113

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.

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

PubMed

Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

2003-12-01

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1 and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.

Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency.

PubMed

Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

2016-01-01

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task-which tapped language comprehension and inference, and modulated sentence congruency-employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency

PubMed Central

Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

2016-01-01

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task—which tapped language comprehension and inference, and modulated sentence congruency—employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation. PMID:27014040

Hedgehog signal transduction: key players, oncogenic drivers, and cancer therapy

PubMed Central

Pak, Ekaterina; Segal, Rosalind A.

2016-01-01

Summary The Hedgehog (Hh) signaling pathway governs complex developmental processes, including proliferation and patterning within diverse tissues. These activities rely on a tightly-regulated transduction system that converts graded Hh input signals into specific levels of pathway activity. Uncontrolled activation of Hh signaling drives tumor initiation and maintenance. However, recent entry of pathway-specific inhibitors into the clinic reveals mixed patient responses and thus prompts further exploration of pathway activation and inhibition. In this review, we share emerging insights on regulated and oncogenic Hh signaling, supplemented with updates on the development and use of Hh pathway-targeted therapies. PMID:27554855

Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4(+) T-cells in respiratory allergies.

PubMed

Karaki, S; Garcia, G; Tcherakian, C; Capel, F; Tran, T; Pallardy, M; Humbert, M; Emilie, D; Godot, V

2014-05-01

Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4(+) T-cells (IL-10-Tregs ) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs . We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs . We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs . This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs . We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation.

PubMed

Moons, Wesley G; Shields, Grant S

2015-08-01

Psychological stressors reliably trigger systemic inflammatory activity as indexed by levels of proinflammatory cytokines. This experiment demonstrates that one's specific emotional reaction to a stressor may be a significant determinant of whether an inflammatory reaction occurs in response to that stressor. Based on extant correlational evidence and theory, a causal approach was used to determine whether an avoidant emotion (anxiety) triggers more inflammatory activity than an approach emotion (anger). In an experimental design (N = 40), a 3-way Emotion Condition × Time × Analyte interaction revealed that a writing-based anxiety induction, but not a writing-based anger induction, increased mean levels of interferon-γ (IFN- γ) and interleukin-1β (IL-1β), but not interleukin-6 (IL-6) in oral mucous, F(2, 54) = 4.64, p = .01, ηp(²) = .15. Further, self-reported state anxiety predicted elevated levels of proinflammatory cytokines, all ΔR(²) >.06, ps <.04, but self-reported state anger did not. These results constitute the first evidence to our knowledge that specific negative emotions can differentially cause inflammatory activity and support a theoretical model explaining these effects based on the avoidance or approach motivations associated with emotions. (c) 2015 APA, all rights reserved).

Software Acquisition Process (SWAP) Model FY81

DTIC Science & Technology

1982-12-01

experience. In addition, the manpower accounting techniques and the effects of resource limitation are described below. a. Contractor Personnel. Five job...developed are each oriented to a specific type of developmental activity. Between them, they account for all types of activities in the acquisition...manning levels and duration; Decision Box probability; and project staffing levels. They take into account the overall size of the project and the

Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity.

PubMed

Tomankova, Veronika; Liskova, Barbora; Skalova, Lenka; Bartikova, Hana; Bousova, Iva; Jourova, Lenka; Anzenbacher, Pavel; Ulrichova, Jitka; Anzenbacherova, Eva

2015-07-15

Cytochromes P450 (CYPs) are enzymes present from bacteria to man involved in metabolism of endogenous and exogenous compounds incl. drugs. Our objective was to assess whether obesity leads to changes in activities and expression of CYPs in the mouse liver, small intestine and colon. An obese mouse model with repeated injection of monosodium glutamate (MSG) to newborns was used. Controls were treated with saline. All mice were sacrificed at 8 months. In the liver and intestines, levels of CYP mRNA and proteins were analyzed using RT-PCR and Western blotting. Activities of CYP enzymes were measured with specific substrates of human orthologous forms. At the end of the experiment, body weight, plasma insulin and leptin levels as well as the specific content of hepatic CYP enzymes were increased in obese mice. Among CYP enzymes, hepatic CYP2A5 activity, protein and mRNA expression increased most significantly in obese animals. Higher activities and protein levels of hepatic CYP2E1 and 3A in the obese mice were also found. No or a weak effect on CYPs 2C and 2D was observed. In the small intestine and colon, no changes of CYP enzymes were detected except for increased expression of CYP2E1 and decreased expression of CYP3A mRNAs in the colon of the obese mice. Results of our study suggest that the specific content and activities of some liver CYP enzymes (especially CYP2A5) can be increased in obese mice. Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, methoxyflurane). Copyright © 2015 Elsevier Inc. All rights reserved.

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

PubMed Central

La Rosa, Corinna; Limaye, Ajit P.; Krishnan, Aparna; Blumstein, Gideon; Longmate, Jeff; Diamond, Don J.

2012-01-01

Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune-priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R−) of a SOT from a seropositive donor (D+). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is overexpressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D+R− patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D+R− patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which however showed exhaustion phenotypes. PMID:21672050

Where are the NGOs and why? The distribution of health and development NGOs in Bolivia.

PubMed

Galway, Lindsay P; Corbett, Kitty K; Zeng, Leilei

2012-11-23

The presence and influence of nongovernmental organizations (NGOs) in the landscape of global health and development have dramatically increased over the past several decades. The distribution of NGO activity and the ways in which contextual factors influence the distribution of NGO activity across geographies merit study. This paper explores the distribution of NGO activity, using Bolivia as a case study, and identifies local factors that are related to the distribution of NGO activity across municipalities in Bolivia. The research question is addressed using a geographic information system (GIS) and multiple regression analyses of count data. We used count data of the total number of NGO projects across Bolivian municipalities to measure NGO activity both in general and in the health sector specifically and national census data for explanatory variables of interest. This study provides one of the first empirical analyses exploring factors related to the distribution of NGO activity at the national scale. Our analyses show that NGO activity in Bolivia, both in general and health-sector specific, is distributed unevenly across the country. Results indicate that NGO activity is related to population size, extent of urbanization, size of the indigenous population, and health system coverage. Results for NGO activity in general and health-sector specific NGO activity were similar. The uneven distribution of NGO activity may suggest a lack of co-ordination among NGOs working in Bolivia as well as a lack of co-ordination among NGO funders. Co-ordination of NGO activity is most needed in regions characterized by high NGO activity in order to avoid duplication of services and programmes and inefficient use of limited resources. Our findings also indicate that neither general nor health specific NGO activity is related to population need, when defined as population health status or education level or poverty levels. Considering these results we discuss broader implications for global health and development and make several recommendations relevant for development and health practice and research.

Where are the NGOs and why? The distribution of health and development NGOs in Bolivia

PubMed Central

2012-01-01

Background The presence and influence of nongovernmental organizations (NGOs) in the landscape of global health and development have dramatically increased over the past several decades. The distribution of NGO activity and the ways in which contextual factors influence the distribution of NGO activity across geographies merit study. This paper explores the distribution of NGO activity, using Bolivia as a case study, and identifies local factors that are related to the distribution of NGO activity across municipalities in Bolivia. Methods The research question is addressed using a geographic information system (GIS) and multiple regression analyses of count data. We used count data of the total number of NGO projects across Bolivian municipalities to measure NGO activity both in general and in the health sector specifically and national census data for explanatory variables of interest. Results This study provides one of the first empirical analyses exploring factors related to the distribution of NGO activity at the national scale. Our analyses show that NGO activity in Bolivia, both in general and health-sector specific, is distributed unevenly across the country. Results indicate that NGO activity is related to population size, extent of urbanization, size of the indigenous population, and health system coverage. Results for NGO activity in general and health-sector specific NGO activity were similar. Conclusions The uneven distribution of NGO activity may suggest a lack of co-ordination among NGOs working in Bolivia as well as a lack of co-ordination among NGO funders. Co-ordination of NGO activity is most needed in regions characterized by high NGO activity in order to avoid duplication of services and programmes and inefficient use of limited resources. Our findings also indicate that neither general nor health specific NGO activity is related to population need, when defined as population health status or education level or poverty levels. Considering these results we discuss broader implications for global health and development and make several recommendations relevant for development and health practice and research. PMID:23173815

Errors and conflict at the task level and the response level.

PubMed

Desmet, Charlotte; Fias, Wim; Hartstra, Egbert; Brass, Marcel

2011-01-26

In the last decade, research on error and conflict processing has become one of the most influential research areas in the domain of cognitive control. There is now converging evidence that a specific part of the posterior frontomedian cortex (pFMC), the rostral cingulate zone (RCZ), is crucially involved in the processing of errors and conflict. However, error-related research has focused primarily on a specific error type, namely, response errors. The aim of the present study was to investigate whether errors on the task level rely on the same neural and functional mechanisms. Here we report a dissociation of both error types in the pFMC: whereas response errors activate the RCZ, task errors activate the dorsal frontomedian cortex. Although this last region shows an overlap in activation for task and response errors on the group level, a closer inspection of the single-subject data is more in accordance with a functional anatomical dissociation. When investigating brain areas related to conflict on the task and response levels, a clear dissociation was perceived between areas associated with response conflict and with task conflict. Overall, our data support a dissociation between response and task levels of processing in the pFMC. In addition, we provide additional evidence for a dissociation between conflict and errors both at the response level and at the task level.

Using semantic technologies and the OSU ontology for modelling context and activities in multi-sensory surveillance systems

NASA Astrophysics Data System (ADS)

Gómez A, Héctor F.; Martínez-Tomás, Rafael; Arias Tapia, Susana A.; Rincón Zamorano, Mariano

2014-04-01

Automatic systems that monitor human behaviour for detecting security problems are a challenge today. Previously, our group defined the Horus framework, which is a modular architecture for the integration of multi-sensor monitoring stages. In this work, structure and technologies required for high-level semantic stages of Horus are proposed, and the associated methodological principles established with the aim of recognising specific behaviours and situations. Our methodology distinguishes three semantic levels of events: low level (compromised with sensors), medium level (compromised with context), and high level (target behaviours). The ontology for surveillance and ubiquitous computing has been used to integrate ontologies from specific domains and together with semantic technologies have facilitated the modelling and implementation of scenes and situations by reusing components. A home context and a supermarket context were modelled following this approach, where three suspicious activities were monitored via different virtual sensors. The experiments demonstrate that our proposals facilitate the rapid prototyping of this kind of systems.

The Realities of a New Senior-Level IT Position.

ERIC Educational Resources Information Center

Bucher, John; Horgan, Barbara; Moberg, Thomas; Paterson, Robert; Todd, H. David

2001-01-01

Focuses on specific actions and activities that a senior-level information technology manager in higher education, such as a chief information officer, might use after starting a new job to help ensure his or her success. (EV)

Gene–Physical Activity Interactions: Overview of Human Studies

PubMed Central

Rankinen, Tuomo; Bouchard, Claude

2009-01-01

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

Interfacial binding of cutinase rather than its catalytic activity determines the steady state interfacial tension during oil drop lipid hydrolysis.

PubMed

Flipsen, J A; van Schaick, M A; Dijkman, R; van der Hijden, H T; Verheij, H M; Egmond, M R

1999-02-01

Hydrolysis of triglycerides by cutinase from Fusarium solani pisi causes in oil drop tensiometer experiments a decrease of the interfacial tension. A series of cutinase variants with amino acid substitutions at its molecular surface yielded different values of the steady state interfacial tension. This tension value poorly correlated with the specific activity as such nor with the total activity (defined as the specific activity multiplied by the amount of enzyme bound) of the cutinase variants. Moreover, it appeared that at activity levels above 15% of that of wild type cutinase the contribution of hydrolysis to the decrease of the tension is saturating. A clear positive correlation was found between the interfacial tension plateau value and the interfacial binding of cutinase, as determined with attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR). These results indicate that the interfacial steady state level is not determined by the rate of hydrolysis, but mainly by the interfacial binding of cutinase.

Operant Conditioning of Primate Prefrontal Neurons

PubMed Central

Schultz, Wolfram; Sakagami, Masamichi

2010-01-01

An operant is a behavioral act that has an impact on the environment to produce an outcome, constituting an important component of voluntary behavior. Because the environment can be volatile, the same action may cause different consequences. Thus to obtain an optimal outcome, it is crucial to detect action–outcome relationships and adapt the behavior accordingly. Although prefrontal neurons are known to change activity depending on expected reward, it remains unknown whether prefrontal activity contributes to obtaining reward. We investigated this issue by setting variable relationships between levels of single-neuron activity and rewarding outcomes. Lateral prefrontal neurons changed their spiking activity according to the specific requirements for gaining reward, without the animals making a motor response. Thus spiking activity constituted an operant response. Data from a control task suggested that these changes were unlikely to reflect simple reward predictions. These data demonstrate a remarkable capacity of prefrontal neurons to adapt to specific operant requirements at the single-neuron level. PMID:20107129

Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro.

PubMed

Sun, Chunhui; Wang, Nan; Huang, Jie; Xin, Jie; Peng, Fen; Ren, Yinshi; Zhang, Shangli; Miao, Junying

2009-10-01

Bone marrow stromal cells (BMSCs) can proliferate in vitro and can be transplanted for treating many kinds of diseases. However, BMSCs become senescent with long-term culture, which inhibits their application. To understand the mechanism underlying the senescence, we investigated the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) and levels of integrin beta4, caveolin-1 and ROS with BMSC senescence. The activity of PC-PLC and levels of integrin beta4, caveolin-1 and ROS increased greatly during cell senescence. Selective inhibition of increased PC-PLC activity with D609 significantly decreased the number of senescence-associated beta galactosidase positive cells in BMSCs. Furthermore, D609 restored proliferation of BMSCs and their differentiation into adipocytes. Moreover, D609 suppressed the elevated levels of integrin beta4, caveolin-1 and ROS. The data suggest that PC-PLC is involved in senescence of BMSCs, and its function is associated with integrin beta4, caveolin-1 and ROS. (c) 2009 Wiley-Liss, Inc.

10-year cumulative and bidirectional associations of domain-specific physical activity and sedentary behaviour with health-related quality of life in French adults: Results from the SU.VI.MAX studies.

PubMed

Omorou, Abdou Y; Vuillemin, Anne; Menai, Medhi; Latarche, Clotilde; Kesse-Guyot, Emmanuelle; Galan, Pilar; Hercberg, Serge; Oppert, Jean-Michel; Briançon, Serge

2016-07-01

The directionality of the associations of domain-specific physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) in adults remain insufficiently known. This study investigated the longitudinal associations of 10-year cumulative levels of PA and SB with HRQoL and the reverse associations. A sample of 2093 (47.8% men) participants from a cohort of French adult (SU.VI.MAX) was included. Data were collected at 3 time points (1998, 2001 and 2007) using the Modifiable Activity Questionnaire (MAQ) for PA (leisure-time and occupational) and SB (screen-viewing, reading and total sitting time) and the DUKE Health Profile for HRQoL. The cumulative level (from 0 to 3) referred to the number of time points where a high PA level, high SB or good HRQoL was reported. Regression models examined the 10-year cumulative level of PA, SB as predictors of HRQoL and reverse associations. The 10-year cumulative level of high PA, both leisure-time and occupational, predicted a higher HRQoL while the 10-year cumulative level of high screen-viewing time and high total sitting time was associated with lower HRQoL. For the reverse association, cumulative level of good HRQoL predicted more leisure-time PA, less screen-viewing time and less total sitting time but was not related to occupational PA. Relationships between PA, SB and HRQoL are complex and should not be oversimplified in one or the other direction. Taking into account domain-specific PA and SB in health promotion programs appears of prime importance to design interventions aiming at improving HRQoL. Copyright © 2016 Elsevier Inc. All rights reserved.

Course-Specific Motivated Learning and Outcomes: The Role of the Perceived Task Value of Course-Specific Assignments

ERIC Educational Resources Information Center

Ling-yee, Esther Li

2011-01-01

Although the internationalization of curricula has increased steadily over the past 30 years, most universities and business schools have concentrated their efforts on program assessment activities, leaving course-level assessment as a gap in most international business assessment portfolios. To address the gap in aligning course-specific designs…

[Gender-specific manifestations of daily physical activity and sedentary behaviour in elderly people of Surgut].

PubMed

Loginov, S I; Malkov, M N; Nikolayev, A Yu

2017-01-01

Objective of the study was to establish gender-specific characteristics of physical activity (PA) and sedentary behavior in elderly people living in Yugra North. 295 residents of Surgut (102 men aged 62,9±5,3 years, 35%; 193 women aged 61,9±3,8 years, 65%) were subject to a IPAQ-RU questionnaire. The study revealed the gender-specific differences in body length and mass, body mass and body fat indices. It was detected that more energy is spent on the housework and physical activity in the country (moderate-intensity physical activity for women and high-intensity one for men). The study data showed no statistically significant gender-specific differences in general physical activity. Sedentary behavior is more popular among men rather than women (2543 vs 2441 min/week). 47% of low-active men and 56% of women reported the sitting times of 6-9 hours per day, 42% - 9-12 hours per day. Actions need to be taken to increase physical activity which is low at the moment and decrease sedentary behavior which is currently on the high level.

Tissue-specific changes of glutamine synthetase activity in oats after rhizosphere infestation by Pseudomonas syringae pv. tabaci. Final report

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

Knight, T.J.; Temple, S.; Sengupta-Gopalan, C.

1996-05-15

Oats (Avena sativa L. lodi) tolerant of rhizosphere infestation by Pseudomonas syringae pv. tabaci when challenged by the pathogen experience tissue-specific alterations of ammonia assimilatory capabilities. Altered ammonia assimilatory potentials between root and leaf tissue result from selective inactivation of glutamine synthetase (GS) by the toxin Tabtoxinine-B-lactam (TBL). Root GS is sensitive and leaf GSs are resistant to TBL inactivation. With prolonged challenge by the pathogen root GS activity decreases but leaf GS specific activity increase. Higher leaf GS activity is due to decreased rates of degradation rather than increased GS synthesis. Higher leaf GS activity and elevated levels ofmore » GS polypeptide appear to result from a limited interaction between GS and TBL leading to the accumulation of a less active but more stable GS holoenzyme. Tolerant challenged oats besides surviving rhizosphere infestation, experience enhanced growth. A strong correlation exists between leaf GS activity and whole plant fresh weight, suggesting that tissue-specific changes in ammonia assimilatory capability provides the plant a more efficient mechanism for uptake and utilization of nitrogen.« less

Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye.

PubMed

Johnston, Robert J; Otake, Yoshiaki; Sood, Pranidhi; Vogt, Nina; Behnia, Rudy; Vasiliauskas, Daniel; McDonald, Elizabeth; Xie, Baotong; Koenig, Sebastian; Wolf, Reinhard; Cook, Tiffany; Gebelein, Brian; Kussell, Edo; Nakagoshi, Hideki; Desplan, Claude

2011-06-10

How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification. Copyright © 2011 Elsevier Inc. All rights reserved.

Does level of specificity affect measures of motivation to comply? A randomized evaluation.

PubMed

Branscum, Paul; Senkowski, Valerie

2018-05-30

The theory of planned behavior (TPB) is a popular value-expectancy model in social and behavioral health. Motivation to comply, one of the theory's constructs, has not been well operationalized and measured in the past, and to date, there has been no assessment of whether level of specificity affects the measurement of the construct. The purpose of this study was to measure the motivation to comply construct across four domains (from general to TACT-behavior specific) and evaluate the potential impact the differences have when identifying determinants of generalized injunctive norms. Students (n = 234) attending a large southwestern university completed a TPB survey related to sleep and physical activity, and were randomized to one of four domains that measured motivation to comply (General domain, n = 58; Health domain, n = 60; Behavioral domain, n = 56; and TACT domain, n = 60). Across both behaviors, motivation to comply measurements did not appear to be affected by changing the level of specificity. Referents for sleep and physical activity were mostly significant, but the effects were small to medium. Future researchers should consider removing motivation to comply measures from TPB surveys to reduce respondent burden or find alternative ways of measuring the construct.

CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

PubMed

Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

2013-07-01

Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

Studies of EBV-lymphoid cell interactions in two patients with the X-linked lymphoproliferative syndrome: normal EBV-specific HLA-restricted cytotoxicity.

PubMed

Rousset, F; Souillet, G; Roncarolo, M G; Lamelin, J P

1986-02-01

Two X-linked lymphoproliferative syndrome (XLP) patients with the hypogammaglobulinemia phenotype were investigated at a time remote from their primary infection with the Epstein-Barr virus (EBV). The lymphoblastoid cell lines derived from these patients expressed the phenotypic markers characteristic of normal mature B lymphocytes and produced normal levels of immunoglobulins (Ig). These observations imply that at least some of their B cells are phenotypically normal. The natural killer (NK) activity of the two patients was low. In one patient, activated lymphocyte killer (ALK) activity was inefficient. These two XLP patients expressed a normal EBV-specific, HLA-restricted cytotoxic activity. It thus appears, from the present findings and those in cases published previously (6/11 patients expressing normal EBV-specific cytotoxic activity), that the notion of poor specific T cell memory for EBV may not be as pivotal ass suggested or, alternatively, that this defect may not be common in hypogammaglobulinemic survivors.

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

Liu Qingfeng; Shao Xiayan; Chen Jie

Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain weremore » measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-{alpha} level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.« less

The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer

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

Jaynes, J.B.; Johnson, J.E.; Buskin, J.N.

1988-01-01

Muscle creatine kinase (MCK) is induced to high levels during skeletal muscle differentiation. The authors examined the upstream regulatory elements of the mouse MCK gene which specify its activation during myogenesis in culture. Fusion genes containing up to 3,300 nucleotides (nt) of MCK 5' flanking DNA in various positions and orientations relative to the bacterial chloramphenicol acetyltransferase (CAT) structural gene were transfected into cultured cells. Transient expression of CAT was compared between proliferating and differentiated MM14 mouse myoblasts and with nonmyogenic mouse L cells. The major effector of high-level expression was found to have the properties of a transcriptional enhancer.more » This element, located between 1,050 and 1,256 nt upstream of the transcription start site, was also found to have a major influence on the tissue and differentiation specificity of MCK expression; it activated either the MCK promoter or heterologous promoters only in differentiated muscle cells. Comparisons of viral and cellular enhancer sequences with the MCK enhancer revealed some similarities to essential regions of the simian virus 40 enhancer as well as to a region of the immunoglobulin heavy-chain enhancer, which has been implicated in tissue-specific protein binding. Even in the absence of the enhancer, low-level expression from a 776-nt MCK promoter retained differentiation specificity. In addition to positive regulatory elements, our data provide some evidence for negative regulatory elements with activity in myoblasts. These may contribute to the cell type and differentiation specificity of MCK expression.« less

CATALASE AND SUPEROXIDE DISMUTASE OF ROOT-COLONIZING SAPROPHYTIC FLUORESCENT PSEUDOMONADS

EPA Science Inventory

Root-colonizing, saprophytic fluorescent pseudomonads of the Pseudomonas putida-P. fluorescens group express similar levels of catalase and superoxide dismutase activities during growth on a sucrose- and amino acid-rich medium. ncreased specific activities of catalase but not sup...

Induced Radioactivity in Recovered Skylab Materials. [gamma ray spectra

NASA Technical Reports Server (NTRS)

Fishman, G. J.; Meegan, C. A.

1980-01-01

Four radioactive isotopes found in aluminum and stainless steel samples from Skylab debris were recovered in Australia. The low-level activity was induced by high-energy protons and neutrons in the space environment. Measurements of the specific activities are given.

Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase

PubMed Central

Garcin, Elsa D.; Arvai, Andrew S.; Rosenfeld, Robin J.; Kroeger, Matt D.; Crane, Brian R.; Andersson, Gunilla; Andrews, Glen; Hamley, Peter J.; Mallinder, Philip R.; Nicholls, David J.; St-Gallay, Stephen A.; Tinker, Alan C.; Gensmantel, Nigel P.; Mete, Antonio; Cheshire, David R.; Connolly, Stephen; Stuehr, Dennis J.; Åberg, Anders; Wallace, Alan V.; Tainer, John A.; Getzoff, Elizabeth D.

2008-01-01

Nitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low levels, and a defensive cytotoxin at higher levels. The high active-site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock, and cancer. Our structural and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a novel specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents towards remote specificity pockets, accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active-site conservation. PMID:18849972

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

PubMed

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

2015-07-01

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

Extravehicular activities limitations study. Volume 1: Physiological limitations to extravehicular activity in space

NASA Technical Reports Server (NTRS)

Furr, Paul A.; Monson, Conrad B.; Santoro, Robert L.; Sears, William J.; Peterson, Donald H.; Smith, Malcolm

1988-01-01

This report contains the results of a comprehensive literature search on physiological aspects of EVA. Specifically, the topics covered are: (1) Oxygen levels; (2) Optimum EVA work; (3) Food and Water; (4) Carbon dioxide levels; (5) Repetitive decompressions; (6) Thermal, and (7) Urine collection. The literature was assessed on each of these topics, followed by statements on conclusions and recommended future research needs.

John Henryism Active Coping, Acculturation, and Psychological Health in Korean Immigrants.

PubMed

Logan, Jeongok G; Barksdale, Debra J; James, Sherman A; Chien, Lung-Chang

2017-03-01

This study aimed to explore the levels of John Henryism (JH) active coping and its association with acculturation status and psychological health (specifically perceived stress, acculturative stress, anxiety, and depression) in Korean immigrants to the United States. In 102 Korean immigrants, JH active coping was measured by the JH Scale; acculturation by the Bidimensional Acculturation Scale; perceived stress by the Perceived Stress Scale; acculturative stress by the Social, Attitudinal, Familial, and Environmental Scale; anxiety by the State Anxiety Subscale of the Spielberger State-Trait Anxiety Inventory; and depression by the Center for Epidemiological Studies Depression Scale. The levels of JH active coping in this sample of Korean immigrants appear to be lower than the levels reported in other racial groups. Independent of demographic factors, JH active coping was a significant predictor of higher acculturation status and better psychological health as indicated by lower levels of perceived stress, acculturative stress, anxiety, and depressive symptoms.

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…

48 CFR 933.103 - Protests to the agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Executive (for protests at the Headquarters level or those specific HCA protests cited in paragraph (i) of this section) or an HCA (for protests at the contracting activity level) will render a decision on a... Headquarters level shall state whether the protester is willing to utilize ADR techniques such as mediation or...

48 CFR 933.103 - Protests to the agency.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Executive (for protests at the Headquarters level or those specific HCA protests cited in paragraph (i) of this section) or an HCA (for protests at the contracting activity level) will render a decision on a... Headquarters level shall state whether the protester is willing to utilize ADR techniques such as mediation or...

Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated ARser81

PubMed Central

Mehraein-Ghomi, Farideh; Church, Dawn R.; Schreiber, Cynthia L.; Weichmann, Ashley M.; Basu, Hirak S.; Wilding, George

2015-01-01

Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21WAF/CIP1, which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21WAF/CIP1, since p21WAF/CIP1 is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth. PMID:26622945

Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells.

PubMed

Penke, Melanie; Schuster, Susanne; Gorski, Theresa; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

2017-10-03

Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes. HepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0.5mM/1mM) as well as nicotinamide mononucleotide (NMN) (0.5 mM) or the specific NAMPT inhibitor FK866 (10nM). Cell survival was measured by WST-1 assay and Annexin V/propidium iodide staining. NAD levels were determined by NAD/NADH Assay or HPLC. Protein and mRNA levels were analysed by Western blot analyses and qPCR, respectively. NAMPT enzyme activity was measured using radiolabelled 14 C-nicotinamide. Lipids were stained by Oil red O staining. Palmitate significantly reduced cell survival and induced apoptosis at physiological doses. NAMPT activity and NAD levels significantly declined after 48h of palmitate. In addition, NAMPT mRNA expression was enhanced which was associated with increased NAMPT release into the supernatant, while intracellular NAMPT protein levels remained stable. Oleate alone did not influence cell viability and NAMPT activity but ameliorated the negative impact of palmitate on cell survival, NAMPT activity and NAD levels, as well as the increased NAMPT mRNA expression and secretion. NMN was able to normalize intracellular NAD levels but did not ameliorate cell viability after co-stimulation with palmitate. FK866, a specific NAMPT inhibitor did not influence lipid accumulation after oleate-treatment. Palmitate targets NAMPT activity with a consequent cellular depletion of NAD. Oleate protects from palmitate-induced apoptosis and variation of NAMPT and NAD levels. Palmitate-induced cell stress leads to an increase of NAMPT mRNA and accumulation in the supernatant. However, the proapoptotic action of palmitate seems not to be mediated by decreased NAD levels.

In the Curriculum. Health: Mental Agility and Memory; Reading/Language Arts: The Writer/Reader Connection; Science: Stars.

ERIC Educational Resources Information Center

Robinson, Alice A.

2003-01-01

Provides six library media activities that are designed for use with specific curriculum units in health, science, language arts, and social studies. Each activity identifies library media skills and curriculum objectives, grade levels, resources, instructional roles, procedures, evaluation guidelines, and follow-up activities. (AEF)

Associations of Acculturation with Self-Report and Objective Physical Activity and Sedentary Behaviors among Latinas

ERIC Educational Resources Information Center

Perez, Lilian G.; Chavez, Adrian; Marquez, David X.; Soto, Sandra C.; Haughton, Jessica; Arredondo, Elva M.

2017-01-01

Background: Less than 50% of Latinas meet physical activity (PA) recommendations. Acculturation is a complex cultural phenomenon that may influence health behaviors, but associations between acculturation and Latinas' activity and sedentary levels are unclear. Aim: To examine associations of acculturation with Latinas' domain-specific and total PA…

Build a Bird House. Grades 3-5.

ERIC Educational Resources Information Center

Rushton, Erik; Ryan, Emily; Swift, Charles

In this activity, students construct bird nests and birdhouses. Students research a bird of their choice in order to design a house that will meet that bird's specific needs. The activity works well in conjunction with a high school level woodshop class where students would partner up. This activity requires an 80-minute time period for…

Anti-acetylcholinesterase and Antioxidant Activities of Inhaled Juniper Oil on Amyloid Beta (1-42)-Induced Oxidative Stress in the Rat Hippocampus.

PubMed

Cioanca, Oana; Hancianu, Monica; Mihasan, Marius; Hritcu, Lucian

2015-05-01

Juniper volatile oil is extracted from Juniperus communis L., of the Cupressaceae family, also known as common juniper. Also, in aromatherapy the juniper volatile oil is used against anxiety, nervous tension and stress-related conditions. In the present study, we identified the effects of the juniper volatile oil on amyloid beta (1-42)-induced oxidative stress in the rat hippocampus. Rats received a single intracerebroventricular injection of amyloid beta (1-42) (400 pmol/rat) and then were exposed to juniper volatile oil (200 μl, either 1 or 3 %) for controlled 60 min period, daily, for 21 continuous days. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Additionally, the acetylcholinesterase activity in the hippocampus was assessed. The amyloid beta (1-42)-treated rats exhibited the following: increase of the acetylcholinesterase, superoxide dismutase and catalase specific activities, decrease of glutathione peroxidase specific activity and the total content of the reduced glutathione along with an elevation of malondialdehyde and protein carbonyl levels. Inhalation of the juniper volatile oil significantly decreases the acetylcholinesterase activity and exhibited antioxidant potential. These findings suggest that the juniper volatile oil may be a potential candidate for the development of therapeutic agents to manage oxidative stress associated with Alzheimer's disease through decreasing the activity of acetylcholinesterase and anti-oxidative mechanism.

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

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.

Regulation of glutamate level in rat brain through activation of glutamate dehydrogenase by Corydalis ternata.

PubMed

Lee, Kwan Ho; Huh, Jae-Wan; Choi, Myung-Min; Yoon, Seung Yong; Yang, Seung-Ju; Hong, Hea Nam; Cho, Sung-Woo

2005-08-31

When treated with protopine and alkalized extracts of the tuber of Corydalis ternata for one year, significant decrease in glutamate level and increase in glutamate dehydrogenase (GDH) activity was observed in rat brains. The expression of GDH between the two groups remained unchanged as determined by Western and Northern blot analysis, suggesting a post-translational regulation of GDH activity in alkalized extracts treated rat brains. The stimulatory effects of alkalized extracts and protopine on the GDH activity was further examined in vitro with two types of human GDH isozymes, hGDH1 (house-keeping GDH) and hGDH2 (nerve-specific GDH). Alkalized extracts and protopine activated the human GDH isozymes up to 4.8-fold. hGDH2 (nerve- specific GDH) was more sensitively affected by 1 mM ADP than hGDH1 (house-keeping GDH) on the activation by alkalized extracts. Studies with cassette mutagenesis at ADP-binding site showed that hGDH2 was more sensitively regulated by ADP than hGDH1 on the activation by Corydalis ternata. Our results suggest that prolonged exposure to Corydalis ternata may be one of the ways to regulate glutamate concentration in brain through the activation of GDH.

Some medicinal plants as immunostimulant for fish.

PubMed

Dügenci, Süheyla Karataş; Arda, Nazli; Candan, Akin

2003-09-01

Immunostimulant effects of the dietary intake of various medicinal plant extracts on fish, rainbow trout (Oncorhynchus mykiss), were investigated. For this purpose fish were fed with diets containing aqueous extracts of mistletoe (Viscum album), nettle (Urtica dioica), and ginger (Zingiber officinale). Food containing lyophilized extracts of these plants as 0.1 and 1% was used at a rate of 2% of body weight per day for three weeks. At the end of the experimental period, various parameters of non-specific defence mechanisms, including extracellular and intracellular respiratory burst activities, phagocytosis in blood leukocytes and total plasma protein level were examined. Specific growth rates (SGRs) and condition factors (CFs) of the fish were also measured. Plant materials tested for immunostimulatory food additives caused an enhanced extracellular respiratory burst activity (P<0.001) compared to the control group. Especially the rainbow trout fed with a diet containing 1% aqueous extract of powdered ginger roots for three weeks exhibited a significant non-specific immune response. Phagocytosis and extracellular burst activity of blood leukocytes were significantly higher in this group than those in the control group. All plant extracts added to fish diet increased the total protein level in plasma except 0.1% ginger. The highest level of plasma proteins was observed in the group fed with 1% ginger extract containing feed.

Urban Transportation Renewal.

ERIC Educational Resources Information Center

Wolter, Kurt A.; Foster, Patrick N.

1995-01-01

Describes a learning activity that involves planning a community and then altering the transportation system to meet new specifications. Includes the rationale for the activity, how it fits into the technology education curriculum, and how it was implemented to fit a variety of age and grade levels. (JOW)

Into the Curriculum.

ERIC Educational Resources Information Center

School Library Media Activities Monthly, 1986

1986-01-01

Provides six library media activities designed for use in connection with specific curriculum units in art, science, and social studies. The activities focus on appreciating Georgia O'Keefe, sound travel, rock identification, Thanksgiving customs, state road maps, and world religions. The descriptions include objectives, grade levels,…

Weekday and weekend sedentary time and physical activity in differentially active children.

PubMed

Fairclough, Stuart J; Boddy, Lynne M; Mackintosh, Kelly A; Valencia-Peris, Alexandra; Ramirez-Rico, Elena

2015-07-01

To investigate whether weekday-weekend differences in sedentary time and specific intensities of physical activity exist among children categorised by physical activity levels. Cross-sectional observational study. Seven-day accelerometer data were obtained from 810 English children (n=420 girls) aged 10-11 years. Daily average minday(-1) spent in moderate to vigorous physical activity were calculated for each child. Sex-specific moderate to vigorous physical activity quartile cut-off values categorised boys and girls separately into four graded groups representing the least (Q1) through to the most active (Q4) children. Sex- and activity quartile-specific multilevel linear regression analyses analysed differences in sedentary time, light physical activity, moderate physical activity, vigorous physical activity, and moderate to vigorous physical activity between weekdays and weekends. On weekdays Q2 boys spent longer in light physical activity (p<0.05), Q1 (p<0.001), Q2 boys (p<0.01) did significantly more moderate physical activity, and Q1-Q3 boys accumulated significantly more vigorous physical activity and moderate to vigorous physical activity than at weekends. There were no significant differences in weekday and weekend sedentary time or physical activity for Q4 boys. On weekdays Q2 and Q3 girls accumulated more sedentary time (p<0.05), Q1 and Q2 girls did significantly more moderate physical activity (p<0.05), and Q1-Q3 girls engaged in more vigorous physical activity (p<0.05) and more moderate to vigorous physical activity (p<0.01) than at weekends. Q4 girls' sedentary time and physical activity varied little between weekdays and weekends. The most active children maintained their sedentary time and physical activity levels at weekends, while among less active peers weekend sedentary time and physical activity at all intensities was lower. Low active children may benefit most from weekend intervention strategies. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats

PubMed Central

Shukla, Charu; Koch, Lauren G.; Britton, Steven L.; Cai, Minying; Hruby, Victor J.; Bednarek, Maria; Novak, Colleen M.

2015-01-01

Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of melanocortin peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high- and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT. PMID:26404873

Spoken words can make the invisible visible-Testing the involvement of low-level visual representations in spoken word processing.

PubMed

Ostarek, Markus; Huettig, Falk

2017-03-01

The notion that processing spoken (object) words involves activation of category-specific representations in visual cortex is a key prediction of modality-specific theories of representation that contrasts with theories assuming dedicated conceptual representational systems abstracted away from sensorimotor systems. In the present study, we investigated whether participants can detect otherwise invisible pictures of objects when they are presented with the corresponding spoken word shortly before the picture appears. Our results showed facilitated detection for congruent ("bottle" → picture of a bottle) versus incongruent ("bottle" → picture of a banana) trials. A second experiment investigated the time-course of the effect by manipulating the timing of picture presentation relative to word onset and revealed that it arises as soon as 200-400 ms after word onset and decays at 600 ms after word onset. Together, these data strongly suggest that spoken words can rapidly activate low-level category-specific visual representations that affect the mere detection of a stimulus, that is, what we see. More generally, our findings fit best with the notion that spoken words activate modality-specific visual representations that are low level enough to provide information related to a given token and at the same time abstract enough to be relevant not only for previously seen tokens but also for generalizing to novel exemplars one has never seen before. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

PubMed

Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

2015-12-01

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

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.

Validation of a Fecal Glucocorticoid Assay to Assess Adrenocortical Activity in Meerkats Using Physiological and Biological Stimuli

PubMed Central

Heistermann, Michael; Santema, Peter; Dantzer, Ben; Mausbach, Jelena; Ganswindt, Andre; Manser, Marta B.

2016-01-01

In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach. PMID:27077741

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

Levels and patterns of objectively-measured physical activity volume and intensity distribution in UK adolescents: the ROOTS study

PubMed Central

2014-01-01

Background Few studies have quantified levels of habitual physical activity across the entire intensity range. We aimed to describe variability in total and intensity-specific physical activity levels in UK adolescents across gender, socio-demographic, temporal and body composition strata. Methods Physical activity energy expenditure and minutes per day (min/d) spent sedentary and in light, moderate, and vigorous intensity physical activity were assessed in 825 adolescents from the ROOTS study (43.5% boys; mean age 15.0 ± 0.30 years), by 4 days of individually calibrated combined heart rate and movement sensing. Measurement days were classified as weekday or weekend and according to the three school terms: summer (April-July), autumn (September-December), and spring (January-March). Gender and age were self-reported and area-level SES determined by postcode data. Body composition was measured by anthropometry and bio-electrical impedance. Variability in physical activity and sedentary time was analysed by linear multilevel modelling, and logistic multilevel regression was used to determine factors associated with physical inactivity (<60 min moderate-to-vigorous intensity physical activity/d). Results During awake hours (15.8 ± 0.9 hrs/d), adolescents primarily engaged in light intensity physical activity (517 min/d) and sedentary time (364 min/d). Boys were consistently more physically active and less sedentary than girls, but gender differences were smaller at weekends, as activity levels in boys dropped more markedly when transitioning from weekday to weekend. Boys were more sedentary on both weekend days compared to during the week, whereas girls were more sedentary on Sunday but less sedentary on Saturday. In both genders light intensity physical activity was lower in spring, while moderate physical activity was lower in autumn and spring terms, compared to the summer term; sedentary time was also higher in spring than summer term. Adolescents with higher fatness engaged in less vigorous intensity physical activity. Factors associated with increased odds of physical inactivity were female gender, both weekend days in boys, and specifically Sunday in girls. Conclusions Physical activity components vary by gender, temporal factors and body composition in UK adolescents. The available data indicate that in adolescence, girls should be the primary targets of interventions designed to increase physical activity levels. PMID:24564949

Levels and patterns of objectively-measured physical activity volume and intensity distribution in UK adolescents: the ROOTS study.

PubMed

Collings, Paul J; Wijndaele, Katrien; Corder, Kirsten; Westgate, Kate; Ridgway, Charlotte L; Dunn, Valerie; Goodyer, Ian; Ekelund, Ulf; Brage, Soren

2014-02-24

Few studies have quantified levels of habitual physical activity across the entire intensity range. We aimed to describe variability in total and intensity-specific physical activity levels in UK adolescents across gender, socio-demographic, temporal and body composition strata. Physical activity energy expenditure and minutes per day (min/d) spent sedentary and in light, moderate, and vigorous intensity physical activity were assessed in 825 adolescents from the ROOTS study (43.5% boys; mean age 15.0 ± 0.30 years), by 4 days of individually calibrated combined heart rate and movement sensing. Measurement days were classified as weekday or weekend and according to the three school terms: summer (April-July), autumn (September-December), and spring (January-March). Gender and age were self-reported and area-level SES determined by postcode data. Body composition was measured by anthropometry and bio-electrical impedance. Variability in physical activity and sedentary time was analysed by linear multilevel modelling, and logistic multilevel regression was used to determine factors associated with physical inactivity (<60 min moderate-to-vigorous intensity physical activity/d). During awake hours (15.8 ± 0.9 hrs/d), adolescents primarily engaged in light intensity physical activity (517 min/d) and sedentary time (364 min/d). Boys were consistently more physically active and less sedentary than girls, but gender differences were smaller at weekends, as activity levels in boys dropped more markedly when transitioning from weekday to weekend. Boys were more sedentary on both weekend days compared to during the week, whereas girls were more sedentary on Sunday but less sedentary on Saturday. In both genders light intensity physical activity was lower in spring, while moderate physical activity was lower in autumn and spring terms, compared to the summer term; sedentary time was also higher in spring than summer term. Adolescents with higher fatness engaged in less vigorous intensity physical activity. Factors associated with increased odds of physical inactivity were female gender, both weekend days in boys, and specifically Sunday in girls. Physical activity components vary by gender, temporal factors and body composition in UK adolescents. The available data indicate that in adolescence, girls should be the primary targets of interventions designed to increase physical activity levels.

A calibration protocol for population-specific accelerometer cut-points in children.

PubMed

Mackintosh, Kelly A; Fairclough, Stuart J; Stratton, Gareth; Ridgers, Nicola D

2012-01-01

To test a field-based protocol using intermittent activities representative of children's physical activity behaviours, to generate behaviourally valid, population-specific accelerometer cut-points for sedentary behaviour, moderate, and vigorous physical activity. Twenty-eight children (46% boys) aged 10-11 years wore a hip-mounted uniaxial GT1M ActiGraph and engaged in 6 activities representative of children's play. A validated direct observation protocol was used as the criterion measure of physical activity. Receiver Operating Characteristics (ROC) curve analyses were conducted with four semi-structured activities to determine the accelerometer cut-points. To examine classification differences, cut-points were cross-validated with free-play and DVD viewing activities. Cut-points of ≤ 372, >2160 and >4806 counts • min(-1) representing sedentary, moderate and vigorous intensity thresholds, respectively, provided the optimal balance between the related needs for sensitivity (accurately detecting activity) and specificity (limiting misclassification of the activity). Cross-validation data demonstrated that these values yielded the best overall kappa scores (0.97; 0.71; 0.62), and a high classification agreement (98.6%; 89.0%; 87.2%), respectively. Specificity values of 96-97% showed that the developed cut-points accurately detected physical activity, and sensitivity values (89-99%) indicated that minutes of activity were seldom incorrectly classified as inactivity. The development of an inexpensive and replicable field-based protocol to generate behaviourally valid and population-specific accelerometer cut-points may improve the classification of physical activity levels in children, which could enhance subsequent intervention and observational studies.

A framework for evaluating national space activity

NASA Astrophysics Data System (ADS)

Wood, Danielle; Weigel, Annalisa

2012-04-01

Space technology and resources are used around the world to address societal challenges. Space provides valuable satellite services, unique scientific discoveries, surprising technology applications and new economic opportunities. Many developing countries formally recognize the advantages of space resources and pursue national level activity to harness them. There is limited data or documentation on the space activities of developing countries. Meanwhile, traditional approaches to summarize national space activity do not necessarily capture the types of activity that developing countries pursue in space. This is especially true if they do not have a formal national space program or office. Developing countries pursue national space activity through activities of many types—from national satellite programs to commercial use of satellite services to involvement with international space institutions. This research aims to understand and analyze these trends. This paper introduces two analytical frameworks for evaluating space activity at the national level. The frameworks are specifically designed to capture the activity of countries that have traditionally been less involved in space. They take a broad view of space related activity across multiple societal sectors and disciplines. The discussion explains the approach for using the frameworks as well as illustrative examples of how they can be applied as part of a research process. The first framework is called the Mission and Management Ladders. This framework considers specific space projects within countries and ranks them on "Ladders" that measure technical challenge and managerial autonomy. This first method is at a micro level of analysis. The second framework is called the Space Participation Metric (SPM). The SPM can be used to assign a Space Participation score to countries based on their involvement in various space related activities. This second method uses a macro level of analysis. The authors developed both frameworks as part of a long term research program about the space activities of developing countries. This aspect of the research focuses on harnessing multiple techniques to summarize complex, multi-disciplinary information about global space activity.

A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

PubMed Central

Qi, Bin; Kniazeva, Marina; Han, Min

2017-01-01

To survive challenging environments, animals acquired the ability to evaluate food quality in the intestine and respond to nutrient deficiencies with changes in food-response behavior, metabolism and development. However, the regulatory mechanisms underlying intestinal sensing of specific nutrients, especially micronutrients such as vitamins, and the connections to downstream physiological responses in animals remain underexplored. We have established a system to analyze the intestinal response to vitamin B2 (VB2) deficiency in Caenorhabditis elegans, and demonstrated that VB2 level critically impacts food uptake and foraging behavior by regulating specific protease gene expression and intestinal protease activity. We show that this impact is mediated by TORC1 signaling through reading the FAD-dependent ATP level. Thus, our study in live animals uncovers a VB2-sensing/response pathway that regulates food-uptake, a mechanism by which a common signaling pathway translates a specific nutrient signal into physiological activities, and the importance of gut microbiota in supplying micronutrients to animals. DOI: http://dx.doi.org/10.7554/eLife.26243.001 PMID:28569665

Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis.

PubMed

Wagner, Ernst; Skoumal, M; Bayer, P M; Klaushofer, K

2009-09-01

The aim of this study was to determine the performance of antibodies against mutated citrullinated vimentin (anti-MCV) in comparison with antibodies to cyclic citrullinated peptides (anti-CCP) in patients with rheumatoid arthritis (RA). Serum levels of anti-MCV and anti-CCP were determined in 193 patients with RA and 332 controls, and sensitivity and specificity were calculated. In a separate analysis of 86 patients, the anti-MCV levels were compared to disease activity. Sensitivity of anti-MCV versus anti-CCP was 71.5 and 69.4%, specificity was 81.3 and 97.6%, respectively. The ROC curves showed higher specificity and an advantage of anti-CCP. In seronegative RA patients the sensitivity of anti-MCV was superior over anti-CCP. Anti-MCV positivities also occurred in systemic lupus erythematosus and Sjoegren's syndrome. In a subgroup of 86 RA patients we found a significant correlation between anti-MCV and disease activity. Anti-MCV appears to be an important marker for the diagnosis of RA, and correlates also with disease activity.

Diet and waist-to-hip ratio: important predictors of lipoprotein levels in sedentary and active young men with no evidence of cardiovascular disease.

PubMed

Mansfield, E; McPherson, R; Koski, K G

1999-11-01

Healthy, young men were studied to determine the relationship of energy and nutrient intake and physical activity to concentrations of plasma lipoprotein and cholesteryl ester transfer protein. A cross-sectional study compared active and sedentary male subjects (17 to 35 years old) with no personal or family history of coronary heart disease. Participants kept 20-day food and activity journals. Individual intakes of energy, protein, carbohydrate, fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, dietary fiber, and alcohol were evaluated. Measurements of blood lipids (total cholesterol and triglycerides, high- and low-density lipoprotein cholesterol); apolipoproteins; cholesteryl ester transfer protein; anthropometric variables (body mass index, waist-to-hip ratio, percentage of body fat); and aerobic capacity were taken during fall and spring data collection periods. SUBJECT SELECTION: Subjects were selected on the basis of normal blood lipid levels, absence of underlying disease, and willingness to comply with their current level of physical activity for the duration of the study. Minimal sample size for statistical power was 12 men per group: 12 of 15 subjects who exercised and 13 of 15 subjects who were sedentary completed all phases of the study. Statistical analyses consisted of 2-way analysis of variance (activity level and season). Pearson product moment correlations and multiple regression analyses were conducted to assess whether energy and nutrient intakes, physical activity status, and/or anthropometric variables predicted plasma concentrations of lipids and apolipoproteins. Lower waist-to-hip ratio, and not specifically activity level, was associated with higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of low-density lipoprotein cholesterol (LDL-C). Dietary intake of saturated and monounsaturated fats and alcohol predicted changes in some apolipoprotein and lipoprotein levels. Use of waist-to-hip ratio in the primary prevention of coronary heart disease is a simple and cost-effective measure to predict development of abnormal lipoprotein profiles in young men. Specific dietary recommendations include adoption of a heart-healthy diet with emphasis on monounsaturated fatty acids (10% to 12% of energy or one third of total fat intake) and the suggestion that small amounts of alcohol (< 3 drinks per week) may, indeed, be beneficial. Because alcohol and waist-to-hip ratio were both important predictors of LDL-C level, even in active young men, the consumption of low levels of alcohol may be beneficial only if waist-to-hip ratio is maintained within the healthful range by achieving an appropriate balance of physical activity and macronutrient intake.

Tobacco drought stress responses reveal new targets for Solanaceae crop improvement.

PubMed

Rabara, Roel C; Tripathi, Prateek; Reese, R Neil; Rushton, Deena L; Alexander, Danny; Timko, Michael P; Shen, Qingxi J; Rushton, Paul J

2015-06-30

The Solanaceae are an economically important family of plants that include tobacco (Nicotiana tabacum L.), tomato, and potato. Drought is a major cause of crop losses. We have identified major changes in physiology, metabolites, mRNA levels, and promoter activities during the tobacco response to drought. We have classified these as potential components of core responses that may be common to many plant species or responses that may be family/species-specific features of the drought stress response in tobacco or the Solanaceae. In tobacco the largest increase in any metabolite was a striking 70-fold increase in 4-hydroxy-2-oxoglutaric acid (KHG) in roots that appears to be tobacco/Solanaceae specific. KHG is poorly characterized in plants but is broken down to pyruvate and glyoxylate after the E. coli SOS response to facilitate the resumption of respiration. A similar process in tobacco would represent a mechanism to restart respiration upon water availability after drought. At the mRNA level, transcription factor gene induction by drought also showed both core and species/family specific responses. Many Group IX Subgroup 3 AP2/ERF transcription factors in tobacco appear to play roles in nicotine biosynthesis as a response to herbivory, whereas their counterparts in legume species appear to play roles in drought responses. We observed apparent Solanaceae-specific drought induction of several Group IId WRKY genes. One of these, NtWRKY69, showed ABA-independent drought stress-inducible promoter activity that moved into the leaf through the vascular tissue and then eventually into the surrounding leaf cells. We propose components of a core metabolic response to drought stress in plants and also show that some major responses to drought stress at the metabolome and transcriptome levels are family specific. We therefore propose that the observed family-specific changes in metabolism are regulated, at least in part, by family-specific changes in transcription factor activity. We also present a list of potential targets for the improvement of Solanaceae drought responses.

Level of tissue differentiation influences the activation of a heat-inducible flower-specific system for genetic containment in poplar (Populus tremula L.).

PubMed

Hoenicka, Hans; Lehnhardt, Denise; Nunna, Suneetha; Reinhardt, Richard; Jeltsch, Albert; Briones, Valentina; Fladung, Matthias

2016-02-01

Differentiation level but not transgene copy number influenced activation of a gene containment system in poplar. Heat treatments promoted CRE gene body methylation. The flower-specific transgene deletion was confirmed. Gene flow between genetic modified trees and their wild relatives is still motive of concern. Therefore, approaches for gene containment are required. In this study, we designed a novel strategy for achieving an inducible and flower-specific transgene removal from poplar trees but still expressing the transgene in the plant body. Hence, pollen carrying transgenes could be used for breeding purposes under controlled conditions in a first phase, and in the second phase genetic modified poplars developing transgene-free pollen grains could be released. This approach is based on the recombination systems CRE/loxP and FLP/frt. Both gene constructs contained a heat-inducible CRE/loxP-based spacer sequence for in vivo assembling of the flower-specific FLP/frt system. This allowed inducible activation of gene containment. The FLP/frt system was under the regulation of a flower-specific promoter, either CGPDHC or PTD. Our results confirmed complete CRE/loxP-based in vivo assembling of the flower-specific transgene excision system after heat treatment in all cells for up to 30 % of regenerants derived from undifferentiated tissue cultures. Degradation of HSP::CRE/loxP spacer after recombination but also persistence as extrachromosomal DNA circles were detected in sub-lines obtained after heat treatments. Furthermore, heat treatment promoted methylation of the CRE gene body. A lower methylation level was detected at CpG sites in transgenic sub-lines showing complete CRE/loxP recombination and persistence of CRE/loxP spacer, compared to sub-lines with incomplete recombination. However, our results suggest that low methylation might be necessary but not sufficient for recombination. The flower-specific FLP/frt-based transgene deletion was confirmed in 6.3 % of flowers.

Net superoxide levels: steeper increase with activity in cooler female and hotter male lizards.

PubMed

Ballen, Cissy; Healey, Mo; Wilson, Mark; Tobler, Michael; Wapstra, Erik; Olsson, Mats

2012-03-01

Ectotherms increase their body temperature in response to ambient heat, thereby elevating their metabolic rate. An often inferred consequence of this is an overall upregulation of gene expression and energetic expenditure, and a concomitant increased production of reactive oxygen species (e.g. superoxide) and, perhaps, a shortened lifespan. However, recent work shows that this may be a superficial interpretation. For example, sometimes a reduced temperature may in fact trigger up-regulation of gene expression. We studied temperature and associated activity effects in male and female Australian painted dragon lizards (Ctenophorus pictus) by allowing the lizards to bask for 4 h versus 12 h, and scoring their associated activity (inactive versus active basking and foraging). As predicted, long-basking lizards (hereafter 'hot') showed heightened activity in both sexes, with a more pronounced effect in females. We then tested for sex-specific effects of basking treatment and activity levels on the increase in net levels of superoxide. In males, short-baskers (hereafter 'cold') had significantly more rapidly decreasing levels of superoxide per unit increasing activity than hot males. In females, however, superoxide levels increased faster with increasing activity in the cold than in the hot basking treatment, and females earlier in the ovarian cycle had lower superoxide levels than females closer to ovulation. In short, males and females differ in how their levels of reactive oxygen species change with temperature-triggered activity.

The interplay between physical activity and anxiety sensitivity in fearful responding to carbon dioxide challenge.

PubMed

Smits, Jasper A J; Tart, Candyce D; Rosenfield, David; Zvolensky, Michael J

2011-01-01

Physical activity may confer protective effects in the development of anxiety and its disorders. These effects may be particularly strong among individuals who have elevated levels of anxiety sensitivity (AS; i.e., the fear of somatic arousal), an established cognitive-based risk factor for anxiety and its disorders. The present study performed a laboratory test of the interplay between physical activity and AS. The participants were adults free of Axis I psychopathology (n = 145) who completed measures of physical activity and AS before undergoing a recurrent 20% carbon dioxide-enriched air (CO(2)) challenge. Consistent with the hypothesis, physical activity was significantly related to CO(2) challenge reactivity among persons with elevated levels of AS, at high levels of physical activity (p < .001) but not at low levels of physical activity (p = .90). Also consistent with hypothesis, irrespective of the level of physical activity, physical activity did not relate significantly to CO(2) challenge reactivity among persons with normative levels of AS (p = .28). These findings provide novel empirical insight into the role that physical activity may play in terms of resiliency for the development of anxiety disorders. Specifically, the protective effects of physical activity may only be evident at higher doses and among persons who are at increased risk of developing anxiety disorders because they have elevated AS.

EGSE customization for the Euclid NISP Instrument AIV/AIT activities

NASA Astrophysics Data System (ADS)

Franceschi, E.; Trifoglio, M.; Gianotti, F.; Conforti, V.; Andersen, J. J.; Stephen, J. B.; Valenziano, L.; Auricchio, N.; Bulgarelli, A.; De Rosa, A.; Fioretti, V.; Maiorano, E.; Morgante, G.; Nicastro, L.; Sortino, F.; Zoli, A.; Balestra, A.; Bonino, D.; Bonoli, C.; Bortoletto, F.; Capobianco, V.; Corcione, L.; Dal Corso, F.; Debei, S.; Di Ferdinando, D.; Dusini, S.; Farinelli, R.; Fornari, F.; Giacomini, F.; Guizzo, G. P.; Laudisio, F.; Ligori, S.; Mauri, N.; Medinaceli, E.; Patrizii, L.; Sirignano, C.; Sirri, G.; Stanco, L.; Tenti, M.; Valieri, C.; Ventura, S.

2016-07-01

The Near Infrared Spectro-Photometer (NISP) on board the Euclid ESA mission will be developed and tested at various levels of integration by using various test equipment. The Electrical Ground Support Equipment (EGSE) shall be required to support the assembly, integration, verification and testing (AIV/AIT) and calibration activities at instrument level before delivery to ESA, and at satellite level, when the NISP instrument is mounted on the spacecraft. In the case of the Euclid mission this EGSE will be provided by ESA to NISP team, in the HW/SW framework called "CCS Lite", with a possible first usage already during the Warm Electronics (WE) AIV/AIT activities. In this paper we discuss how we will customize that "CCS Lite" as required to support both the WE and Instrument test activities. This customization will primarily involve building the NISP Mission Information Base (the CCS MIB tables) by gathering the relevant data from the instrument sub-units and validating these inputs through specific tools. Secondarily, it will imply developing a suitable set of test sequences, by using uTOPE (an extension to the TCL scripting language, included in the CCS framework), in order to implement the foreseen test procedures. In addition and in parallel, custom interfaces shall be set up between the CCS and the NI-IWS (the NISP Instrument Workstation, which will be in use at any level starting from the WE activities), and also between the CCS and the TCC (the Telescope Control and command Computer, to be only and specifically used during the instrument level tests).

The association between social cohesion and physical activity in canada: A multilevel analysis.

PubMed

Yip, Calvin; Sarma, Sisira; Wilk, Piotr

2016-12-01

Although previous research has shown that social cohesion may promote physical activity, social cohesion at the individual level was not always differentiated from social cohesion at the community level, and studies were often limited to specific population subgroups or geographical areas. We addressed the above limitations through the use of a multilevel modelling approach and nationally-representative data from the 2009-2014 Canadian Community Health Survey. Physical activity level was operationalized as average daily energy expenditure; social cohesion was assessed by self-rated sense of belonging to the local community; and communities were represented by Canada's Forward Sortation Areas. The sample included 245,150 respondents from 1570 communities. Geographical location was found to explain a significant proportion (4.1%) of the overall variance in physical activity level. After adjusting for age, sex, household income, education and urban-rural status, both individual- and community-level social cohesion were found to be positively associated with physical activity (p<0.001 for both). Thus, efforts to promote social cohesion and integration within communities may also promote physical activity and overall health.

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

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

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Object Categorization: Reversals and Explanations of the Basic-Level Advantage

ERIC Educational Resources Information Center

Rogers, Timothy T.; Patterson, Karalyn

2007-01-01

People are generally faster and more accurate to name or categorize objects at the basic level (e.g., dog) relative to more general (animal) or specific (collie) levels, an effect replicated in Experiment 1 for categorization of object pictures. To some, this pattern suggests a dual-process mechanism, in which objects first activate basic-level…

Outdoor Education Guide-Handbook, Waukesha Public Schools.

ERIC Educational Resources Information Center

Vitale, Joseph A.

Designed by the Waukesha Public Schools (Wisconsin) specifically for an elementary level three-day camping trip at Camp Phantom Lake, this outdoor education guide presents some activities which suggest adaptation. Activity directions, plans, worksheets, evaluation sheets, and illustrations are presented in sequential order for the following…

Learning Behavior Characterization with Multi-Feature, Hierarchical Activity Sequences

ERIC Educational Resources Information Center

Ye, Cheng; Segedy, James R.; Kinnebrew, John S.; Biswas, Gautam

2015-01-01

This paper discusses Multi-Feature Hierarchical Sequential Pattern Mining, MFH-SPAM, a novel algorithm that efficiently extracts patterns from students' learning activity sequences. This algorithm extends an existing sequential pattern mining algorithm by dynamically selecting the level of specificity for hierarchically-defined features…

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

EPA Science Inventory

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

Regulation of Tau Pathology by the Microglial Fractalkine Receptor

PubMed Central

Bhaskar, Kiran; Konerth, Megan; Kokiko-Cochran, Olga N.; Cardona, Astrid; Ransohoff, Richard M.; Lamb, Bruce T.

2010-01-01

SUMMARY Aggregates of the hyperphosphorylated microtubule associated protein tau (MAPT) are an invariant neuropathological feature of tauopathies. Here we show that microglial neuroinflammation promotes MAPT phosphorylation and aggregation. First, lipopolysaccharide-induced microglial activation promotes hyperphosphorylation of endogenous mouse MAPT in non-transgenic mice that is further enhanced in mice lacking the microglial-specific fractalkine receptor (CX3CR1) and is dependent upon functional toll-like receptor 4 and interleukin 1 (IL1) receptors. Second, humanized MAPT transgenic mice lacking CX3CR1 exhibited enhanced MAPT phosphorylation and aggregation as well as behavioral impairments that correlated with increased levels of active p38 MAPK. Third, in vitro experiments demonstrate that microglial activation elevates the level of active p38 MAPK and enhances MAPT hyperphosphorylation within neurons that can be blocked by administration of an interleukin 1 receptor antagonist and a specific p38 MAPK inhibitor. Taken together, our results suggest that CX3CR1 and IL1/p38 MAPK may serve as novel therapeutic targets for human tauopathies. PMID:20920788

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

PubMed Central

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

2008-01-01

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

Evaluation of the Science Enrichment Activities (SEA) Program: A Decision Oriented Model.

ERIC Educational Resources Information Center

Linn, Marcia C.

1978-01-01

Three questions guided an evaluation of sixth and eighth grade science enrichment activities: (1) Does a free choice interactive program affect cognitive abilities? (2) Do students in a free choice program make predictable selections of activities based on their age, sex, or ability level? and (3) Are specific student choices associated with…

Role of Individual and School Factors in Physical Activity Patterns of Secondary-Level Spanish Students

ERIC Educational Resources Information Center

Juan, Francisco Ruiz; Bengoechea, Enrique Garcia; Montes, Maria Elena Garcia; Bush, Paula Louise

2010-01-01

Background: While the importance of individual and school factors as correlates of overall youth physical activity has been demonstrated by previous research, less is known about the relationship of these factors with specific patterns of physical activity during adolescence. Thus, the purpose of this study was to examine the association of…

Physical Activity Patterns and Self-Efficacy of Selected College Students

ERIC Educational Resources Information Center

Hutchins, Matt; Drolet, Judy C.; Ogletree, Roberta J.

2010-01-01

Much attention has been given to the fact that Americans are becoming less active. This study was designed to examine the levels of exercise-specific self-efficacy and physical activity rates in a selected group of college students. Students were recruited as they entered a fitness facility. Participation consisted of completing a survey that…

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

PubMed

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

2017-08-01

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

Cis-regulatory RNA elements that regulate specialized ribosome activity.

PubMed

Xue, Shifeng; Barna, Maria

2015-01-01

Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

Tissue-specific modulation of angiotensin-converting enzyme (ACE) in hyperthyroidism.

PubMed

Carneiro-Ramos, M S; Silva, V B; Santos, R A S; Barreto-Chaves, M L M

2006-11-01

We have previously demonstrated the interaction between the RAS and thyroid hormones (TH). The present study was designed to determine the role of TH in the local regulation of ACE activity and expression in different tissues. Adult male Wistar rats were randomized into three groups: T4-25 and T4-100 (0.025 and 0.100mg/kg of body weight/day of l-thyroxine for 14 days, respectively) and control. Hemodynamic parameters as well as cardiac and renal hypertrophy were evaluated. ACE activity and mRNA levels were determined by Fluorimetric and Northern blot assays, respectively. Both doses increased SBP and HR, as well as inducing cardiac and renal hypertrophy. Pulmonary and serum ACE levels were comparable among the groups. Both doses promoted increased renal ACE activity and expression but surprisingly ACE was diminished in the heart in both hyperthyroid groups. This change was mediated by a tissue-specific transcription mechanism.

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.

Map and Compass Skills for the Secondary School (Understanding Topographic Maps, Developing Compass Skills, and Orienteering). Instructional Activities Series IA/S-18.

ERIC Educational Resources Information Center

Larkin, Robert P.

This activity is one of a series of 17 teacher-developed instructional activities for geography at the secondary-grade level described in SO 009 140. The activity investigates the development of compass skills, map skills, and orienteering. It employs the educational-games approach. Given specific exercises and instructions, students become…

BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

PubMed Central

Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

2015-01-01

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

Built environment interventions aimed at improving physical activity levels in rural Ontario health units: a descriptive qualitative study.

PubMed

Coghill, Cara-Lee; Valaitis, Ruta K; Eyles, John D

2015-05-03

Few studies to date have explored the relationship between the built environment and physical activity specifically in rural settings. The Ontario Public Health Standards policies mandate that health units in Ontario address the built environment; however, it is unclear how public health practitioners are integrating the built environment into public health interventions aimed at improving physical activity in chronic disease prevention programs. This descriptive qualitative study explored interventions that have or are being implemented which address the built environment specifically related to physical activity in rural Ontario health units, and the impact of these interventions. Data were collected through twelve in-depth semi-structured interviews with rural public health practitioners and managers representing 12 of 13 health units serving rural communities. Key themes were identified using qualitative content analysis. Themes that emerged regarding the types of interventions that health units are employing included: Engagement with policy work at a municipal level; building and working with community partners, committees and coalitions; gathering and providing evidence; developing and implementing programs; and social marketing and awareness raising. Evaluation of interventions to date has been limited. Public health interventions, and their evaluations, are complex. Health units who serve large rural populations in Ontario are engaging in numerous activities to address physical activity levels. There is a need to further evaluate the impact of these interventions on population health.

Effects of fulvic acid on growth performance and intestinal health of juvenile loach Paramisgurnus dabryanus (Sauvage).

PubMed

Gao, Yang; He, Jie; He, Zhuliu; Li, Zhiwei; Zhao, Bo; Mu, Yi; Lee, Jeong-Yeol; Chu, Zhangjie

2017-03-01

A 60-day feeding trial was conducted to determine the effect of dietary fulvic acid supplements on intestinal digestive activity (enzymatic analysis), antioxidant activity, immune enzyme activity and microflora composition of juvenile loach (initial weight of 6.2 ± 0.1 g) reared in experimental aquaria. Five test diets containing 0, 0.5, 1.0, 1.5, and 2% fulvic acid were randomly assigned to three aquaria, respectively. Elevated growth performance including final weight, weight gain (WG), specific growth rate (SGR) and feed conversion ratio (FCR) was observed in loaches that were fed fulvic acid. Maximal weight gain rates and specific growth rates occurred at the 1.5% additive level. The optimal dietary fulvic requirement for maximal growth of juvenile loach is 16.4 g per kg of the diet based on the quadratic regression analysis of specific growth rate against dietary fulvic acid levels. Furthermore, intestinal protease activity, antioxidant activity, lysozyme activity (LZM), complement 3 (C3) content, immunoglobulin M (IgM) content, acid phosphatase activity (ACP) and alkaline phosphatase activity (AKP) were significantly elevated with concomitant increasing levels of dietary fulvic acid. Following a deep sequencing analysis, a total of 42,058 valid reads and 609 OTUs (operational taxonomic units) obtained from the control group and the group displaying the most optimal growth rate were analyzed. Fulvic acid supplementation resulted in an abundance of Firmicute and Actinobacteria sequences, with a concomitant reduction in the abundance of Proteobacteria. Results indicated that fulvic acid supplementation resulted in a reduction in the relative abundance of Serratia, Acinetobacter, Aeromonas and Edwardsiella, and a relative increase in the abundance of Lactobacillus in the intestine. In conclusion, these results suggest that fulvic acid improves growth performance and intestinal health condition of loach, indicates that fulvic acid could be used as an immunoenhancer in loach culture. Copyright © 2017. Published by Elsevier Ltd.

Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation

PubMed Central

1994-01-01

Cells of monocytic lineage can initiate extravascular fibrin deposition via expression of blood coagulation mediators. This report is about experiments on three mechanisms with the potential to modulate monocyte- initiated coagulation. Monocyte procoagulant activity was examined as a function of lipid cofactor, protein cofactor, and specific inhibitor expression during short-term culture in vitro. Lipid cofactor activity was measured as the initial rate of factor X activation by intrinsic- pathway components, the assembly of which depends on this cofactor. Lipid cofactor activity levels changed by < 30% during 48-h culture. Protein cofactor, i.e., tissue factor (TF) antigen was measured by enzyme immunoassay. It increased from 461 pg/ml to a maximum value of 3,550 pg/ml at 24 h and remained at 70% of this value. Specific TF activity, measured as factor VII-dependent factor X activation rate, decreased from 54 to 18 nM FXa/min between 24 and 48 h. TF activity did not correlate well with either lipid cofactor or TF protein levels. In contrast, the decrease in TF activity coincided in time with maximal expression of tissue factor pathway inhibitor (TFPI) mRNA, which was determined using reverse transcriptase polymerase chain reaction (RT- PCR), and with maximal TFPI protein levels measured by immunoassay. The number of mRNA copies coding for TFPI and TF in freshly isolated blood monocytes were 46 and 20 copies/cells, respectively. These values increased to 220 and 63 copies/cell during short-term cell culture in the presence of endotoxin. Results demonstrate concomitant expression by monocytes of genes coding for both the essential protein cofactor and the specific inhibitor of the extrinsic coagulation pathway. Together with functional and antigenic analyses, they also imply that the initiation of blood clotting by extravascular monocyte/macrophages can be modulated locally by TFPI independently of plasma sources of the inhibitor. PMID:8195712

Domain-specific physical activity and health-related quality of life in university students.

PubMed

Pedišić, Zeljko; Rakovac, Marija; Titze, Sylvia; Jurakić, Danijel; Oja, Pekka

2014-01-01

Information on the relationship between domain-specific physical activity (PA) and health-related quality of life (HRQoL) in the general population and specific groups is still scarce. The aim of this study was to determine the relationship between PA in work, transport, domestic and leisure-time domains and HRQoL among university students. PA and HRQoL were assessed in a random stratified sample of 1750 university students using the International Physical Activity Questionnaire - long form and 12-item Short Form Health Survey, respectively. The Spearman's rank correlations, adjusted for age, community size, personal monthly budget, body mass index, smoking habits and alcohol intake ranged from -0.11 to 0.18 in female students and -0.29 to 0.19 in male students. Leisure-time, domestic, transport-related PA and total PA were positively related to HRQoL. Inverse correlations with HRQoL were only found for work-related PA in male students. Multiple linear regression analysis showed that only leisure-time PA was related to the Physical Summary Component score (β = 0.08 for females and β = 0.10 for males, P < 0.05). Domain-specific PA levels were not significantly related to the Mental Component Summary score. To get a more comprehensive insight in the relationship between PA and HRQoL, future studies should not only analyse total PA levels but also domain-specific PA levels. The evidence on the positive relationship of leisure-time, transport and domestic PA with HRQoL can potentially be used to support evidence-based promotion of PA in a university setting, and as a hypothesis for future longitudinal studies on such potential causal relationships.

Endurance exercise training induces fat depot-specific differences in basal autophagic activity

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

Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya, E-mail: tizawa@mail.doshisha.ac.jp

The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly highermore » in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased autophagosome associated LC3-II in WAT. • Exercise-induced changes in p62 and ATG7 were WAT-type specific. • Exercise-induced basal autophagic activity shows fat depot-specific differences.« less

Objectively measured physical activity in Danish after-school cares: Does sport certification matter?

PubMed

Domazet, S L; Møller, N C; Støckel, J T; Ried-Larsen, M

2015-12-01

Inactivity and more sedentary time predominate the daily activity level of many of today's children. In Denmark, certified sport after-school cares have been established in order to increase children's daily physical activity (PA) level. This cross-sectional study aimed to investigate the activity level among participants in certified sport after-school cares vs regular after-school cares. The study was carried out in 2011 in 10 after-school cares (5 sport/5 regular) throughout Denmark, whereof 475 children aged 5-11 years participated. PA level was assessed using Actigraph GT3X and GT3X+ activity monitors worn by the children for at least 8 consecutive days. Anthropometry and cardiorespiratory fitness were measured as well. A multivariate regression analysis was carried out to check for the differences in the PA level across the two care systems. However, there did not appear to be any differences in overall PA or in time-specific day parts (e.g., during after-school care). The activity levels were quite similar across after-school cares and were mutually high during time spent in the care facility. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Not Available

The Office of Civilian Radioactive Waste Management Systems Engineering Management Plan (OCRWM SEMP) specifies the technical management approach for the development of the waste management system, and specifies the approach for the development of each of the system elements -- the waste acceptance system, the transportation system, the Monitored Retrievable Storage (MRS) facility, and the mined geologic disposal system, which includes site characterization activity. The SEMP also delineates how systems engineering will be used by OCRWM to describe the system development process; it identifies responsibilities for its implementation, and specifies the minimum requirements for systems engineering. It also identifies themore » close interrelationship of system engineering and licensing processes. This SEMP, which is a combined OCRWM and M&O SEMP, is part of the top-level program documentation and is prepared in accordance with the direction provided in the Program Management System Manual (PMSM). The relationship of this document to other top level documents in the CRWMS document hierarchy is defined in the PMSM. A systems engineering management plan for each project, which specifies the actions to be taken in implementing systems engineering at the project level, shall be prepared by the respective project managers. [``Program`` refers to the CRWMS-wide activity and ``project`` refers to that level responsible for accomplishing the specific activities of that segment of the program.] The requirements for the project level SEMPs are addressed in Section 4.2.2.2. They represent the minimum set of requirements, and do not preclude the broadening of systems engineering activities to meet the specific needs of each project.« less

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting.

PubMed

Farokhimanesh, Samila; Rahbarizadeh, Fatemeh; Rasaee, Mohammad J; Kamali, Abbas; Mashkani, Baratali

2010-01-01

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl-2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual-specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia-responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT-PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase-3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low-potential toxicity for normal tissues.

Societal interventions to prevent child abuse and neglect.

PubMed

Hay, T; Jones, L

1994-01-01

A framework for understanding child maltreatment in terms of complex and interacting factors from the individual to the societal level can aid in conceptualizing and implementing prevention efforts. Research on interventions at the societal level can guide a broad range of activities, increasing their effectiveness and viability. Fundamental approaches include evaluation of specific interventions and systems-level research on implementation and development of best practice in prevention activities for different portions of society. Research can indicate the roles that each individual, agency, organization, community, and level of government can play. The U.N. Convention on the Rights of the Child provides a useful framework for societal level change to improve the welfare of children and families.

GABA predicts inhibition of frequency-specific oscillations in schizophrenia.

PubMed

Rowland, Laura M; Edden, Richard A E; Kontson, Kimberly; Zhu, He; Barker, Peter B; Hong, L Elliot

2013-01-01

This study is the first to show a relationship between in-vivo brain gamma-amino butyric acid (GABA) levels and auditory inhibitory electrophysiological measures in schizophrenia. Results revealed a strong association between GABA levels and gating of the theta-alpha and beta activities in schizophrenia.

USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination.

PubMed

Novellasdemunt, Laura; Foglizzo, Valentina; Cuadrado, Laura; Antas, Pedro; Kucharska, Anna; Encheva, Vesela; Snijders, Ambrosius P; Li, Vivian S W

2017-10-17

The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancers (CRCs), resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of the APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID) in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs. Copyright © 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

Plasticity of brain wave network interactions and evolution across physiologic states

PubMed Central

Liu, Kang K. L.; Bartsch, Ronny P.; Lin, Aijing; Mantegna, Rosario N.; Ivanov, Plamen Ch.

2015-01-01

Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of network connectivity and link strength, while at the same time each frequency-specific network is characterized by a different signature pattern of sleep-stage stratification, reflecting a remarkable flexibility in response to change in physiologic state. These new aspects of neural plasticity demonstrate that in addition to dominant brain waves, the network of brain wave interactions is a previously unrecognized hallmark of physiologic state and function. PMID:26578891

Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise.

PubMed

Pourteymour, Shirin; Hjorth, Marit; Lee, Sindre; Holen, Torgeir; Langleite, Torgrim M; Jensen, Jørgen; Birkeland, Kåre I; Drevon, Christian A; Eckardt, Kristin

2017-10-01

Physical activity promotes specific adaptations in most tissues including skeletal muscle. Acute exercise activates numerous signaling cascades including pathways involving mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK)1/2, which returns to pre-exercise level after exercise. The expression of MAPK phosphatases (MKPs) in human skeletal muscle and their regulation by exercise have not been investigated before. In this study, we used mRNA sequencing to monitor regulation of MKPs in human skeletal muscle after acute cycling. In addition, primary human myotubes were used to gain more insights into the regulation of MKPs. The two ERK1/2-specific MKPs, dual specificity phosphatase 5 (DUSP5) and DUSP6, were the most regulated MKPs in skeletal muscle after acute exercise. DUSP5 expression was ninefold higher immediately after exercise and returned to pre-exercise level within 2 h, whereas DUSP6 expression was reduced by 43% just after exercise and remained below pre-exercise level after 2 h recovery. Cultured myotubes express both MKPs, and incubation with dexamethasone (Dex) mimicked the in vivo expression pattern of DUSP5 and DUSP6 caused by exercise. Using a MAPK kinase inhibitor, we showed that stimulation of ERK1/2 activity by Dex was required for induction of DUSP5 However, maintaining basal ERK1/2 activity was required for basal DUSP6 expression suggesting that the effect of Dex on DUSP6 might involve an ERK1/2-independent mechanism. We conclude that the altered expression of DUSP5 and DUSP6 in skeletal muscle after acute endurance exercise might affect ERK1/2 signaling of importance for adaptations in skeletal muscle during exercise. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

What environmental factors influence resumption of valued activities post stroke: a systematic review of qualitative and quantitative findings.

PubMed

Jellema, Sandra; van Hees, Suzanne; Zajec, Jana; van der Sande, Rob; Nijhuis-van der Sanden, Maria Wg; Steultjens, Esther Mj

2017-07-01

Identify the environmental factors that influence stroke-survivors' reengagement in personally valued activities and determine what specific environmental factors are related to specific valued activity types. PubMed, CINAHL and PsycINFO were searched until June 2016 using multiple search-terms for stroke, activities, disability, and home and community environments. An integrated mixed-method systematic review of qualitative, quantitative and mixed-design studies was conducted. Two researchers independently identified relevant studies, assessed their methodological quality and extracted relevant findings. To validly compare and combine the various findings, all findings were classified and grouped by environmental category and level of evidence. The search yielded 4024 records; 69 studies were included. Most findings came from low-evidence-level studies such as single qualitative studies. All findings were consistent in that the following factors facilitated reengagement post-stroke: personal adapted equipment; accessible environments; transport; services; education and information. Barriers were: others' negative attitudes and behaviour; long distances and inconvenient environmental conditions (such as bad weather). Each type of valued activity, such as mobility or work, had its own pattern of environmental influences, social support was a facilitator to all types of activities. Although in many qualitative studies others' attitudes, behaviour and stroke-related knowledge were seen as important for reengagement, these factors were hardly studied quantitatively. A diversity of environmental factors was related to stroke-survivors' reengagement. Most findings came from low-evidence-level studies so that evidence on causal relationships was scarce. In future, more higher-level-evidence studies, for example on the attitudes of significant others, should be conducted.

Parent-child interactions and objectively measured child physical activity: a cross-sectional study

USDA-ARS?s Scientific Manuscript database

Parents influence their children's behaviors directly through specific parenting practices and indirectly through their parenting style. Some practices such as logistical and emotional support have been shown to be positively associated with child physical activity (PA) levels, while for others (e.g...

Promoting Elementary Physical Education: Results of a School-Based Evaluation Study

ERIC Educational Resources Information Center

Boyle-Holmes, Trina; Grost, Lisa; Russell, Lisa; Laris, B. A.; Robin, Leah; Haller, Elizabeth; Potter, Susan; Lee, Sarah

2010-01-01

Using a quasiexperimental design, the authors examine whether fourth- and fifth-grade students exposed to a developmental physical education (PE) curriculum, Michigan's Exemplary Physical Education Curriculum (EPEC), demonstrated stronger motor skill--specific self-efficacy and perceptions of physical activity competence, physical activity levels,…

Designing collective behavior in a termite-inspired robot construction team.

PubMed

Werfel, Justin; Petersen, Kirstin; Nagpal, Radhika

2014-02-14

Complex systems are characterized by many independent components whose low-level actions produce collective high-level results. Predicting high-level results given low-level rules is a key open challenge; the inverse problem, finding low-level rules that give specific outcomes, is in general still less understood. We present a multi-agent construction system inspired by mound-building termites, solving such an inverse problem. A user specifies a desired structure, and the system automatically generates low-level rules for independent climbing robots that guarantee production of that structure. Robots use only local sensing and coordinate their activity via the shared environment. We demonstrate the approach via a physical realization with three autonomous climbing robots limited to onboard sensing. This work advances the aim of engineering complex systems that achieve specific human-designed goals.

Decoding task-based attentional modulation during face categorization.

PubMed

Chiu, Yu-Chin; Esterman, Michael; Han, Yuefeng; Rosen, Heather; Yantis, Steven

2011-05-01

Attention is a neurocognitive mechanism that selects task-relevant sensory or mnemonic information to achieve current behavioral goals. Attentional modulation of cortical activity has been observed when attention is directed to specific locations, features, or objects. However, little is known about how high-level categorization task set modulates perceptual representations. In the current study, observers categorized faces by gender (male vs. female) or race (Asian vs. White). Each face was perceptually ambiguous in both dimensions, such that categorization of one dimension demanded selective attention to task-relevant information within the face. We used multivoxel pattern classification to show that task-specific modulations evoke reliably distinct spatial patterns of activity within three face-selective cortical regions (right fusiform face area and bilateral occipital face areas). This result suggests that patterns of activity in these regions reflect not only stimulus-specific (i.e., faces vs. houses) responses but also task-specific (i.e., race vs. gender) attentional modulation. Furthermore, exploratory whole-brain multivoxel pattern classification (using a searchlight procedure) revealed a network of dorsal fronto-parietal regions (left middle frontal gyrus and left inferior and superior parietal lobule) that also exhibit distinct patterns for the two task sets, suggesting that these regions may represent abstract goals during high-level categorization tasks.

Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds

PubMed Central

Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

2014-01-01

There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ. PMID:25101049

Roles of unphosphorylated STATs in signaling.

PubMed

Yang, Jinbo; Stark, George R

2008-04-01

The seven members of the signal transducer and activator of transcription (STAT) family of transcription factors are activated in response to many different cytokines and growth factors by phosphorylation of specific tyrosine residues. The STAT1 and STAT3 genes are specific targets of activated STATs 1 and 3, respectively, resulting in large increases in the levels of these unphosphorylated STATs (U-STATs) in response to the interferons (STAT1) or ligands that active gp130, such as IL-6 (STAT3). U-STATs drive gene expression by novel mechanisms distinct from those used by phosphorylated STAT (P-STAT) dimers. In this review, we discuss the roles of U-STATs in transcription and regulation of gene expression.

Stimulus-specific suppression preserves information in auditory short-term memory.

PubMed

Linke, Annika C; Vicente-Grabovetsky, Alejandro; Cusack, Rhodri

2011-08-02

Philosophers and scientists have puzzled for millennia over how perceptual information is stored in short-term memory. Some have suggested that early sensory representations are involved, but their precise role has remained unclear. The current study asks whether auditory cortex shows sustained frequency-specific activation while sounds are maintained in short-term memory using high-resolution functional MRI (fMRI). Investigating short-term memory representations within regions of human auditory cortex with fMRI has been difficult because of their small size and high anatomical variability between subjects. However, we overcame these constraints by using multivoxel pattern analysis. It clearly revealed frequency-specific activity during the encoding phase of a change detection task, and the degree of this frequency-specific activation was positively related to performance in the task. Although the sounds had to be maintained in memory, activity in auditory cortex was significantly suppressed. Strikingly, patterns of activity in this maintenance period correlated negatively with the patterns evoked by the same frequencies during encoding. Furthermore, individuals who used a rehearsal strategy to remember the sounds showed reduced frequency-specific suppression during the maintenance period. Although negative activations are often disregarded in fMRI research, our findings imply that decreases in blood oxygenation level-dependent response carry important stimulus-specific information and can be related to cognitive processes. We hypothesize that, during auditory change detection, frequency-specific suppression protects short-term memory representations from being overwritten by inhibiting the encoding of interfering sounds.

Aeronautics Research and Technology Program and specific objectives, fiscal year 1982

NASA Technical Reports Server (NTRS)

Olstad, W. B.

1981-01-01

The Aeronautics Research and Technology program is broken down into two program areas (research and technology base, and systems technology programs) which are further broken down into succeedingly more detailed activities to form a work breakdown structure for the aeronautics program: program area, program/discipline objective, specific objective, and research and technology objective and plan (RTOP). A detailed view of this work breakdown structure down to the specific objective level is provided, and goals or objectives at each of these levels are set forth. What is to be accomplished and why are addressed, but not how. The letter falls within the domain of the RTOP.

Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

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

Fukuyama, Yoshiko; Tokuhara, Daisuke; Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639

Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FLmore » activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.« less

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

PubMed

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

1991-01-01

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

Correlations between prefrontal neurons form a small-world network that optimizes the generation of multineuron sequences of activity

PubMed Central

Luongo, Francisco J.; Zimmerman, Chris A.; Horn, Meryl E.

2016-01-01

Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g., working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a by-product of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization—they have a small-world topology. However, until now it has not been possible to directly link small-world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate data sets that have identical levels of network activity at every point in time but nevertheless represent various network topologies. We call this method shuffling activity to rearrange correlations (SHARC). We found that only surrogate data sets based on the actual small-world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small-world data sets contained many more sequences than surrogate data sets with randomly arranged correlations. Surprisingly, small-world data sets also outperformed data sets in which correlations were maximally clustered. Thus the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity. PMID:26888108

Let's Go Exploring. Nutrition Comes Alive. Level 1. Nutrition Educator's Guide and Work Sheets, Letters to Parents, Recipes. Revised Edition.

ERIC Educational Resources Information Center

Farrell, Tracy J.

This guide provides a nutrition education program for elementary school students that spans kindergarten through Grade 3 as well as providing activities for specific levels. Nutrition education objectives are stated for each grade level: (1) kindergarten--students will become familiar with and motivated to eat a variety of foods; (2) grade…

Is Collaborative Learners' Adoption of Metacognitive Regulation Related to Students' Content Processing Strategies and the Level of Transactivity in Their Peer Discussions?

ERIC Educational Resources Information Center

De Backer, Liesje; Van Keer, Hilde; Valcke, Martin

2017-01-01

The present study investigates collaborative learners' adoption of key regulation activities (i.e., orienting, planning, monitoring, and evaluating) and a deep-level regulation approach in relation to characteristics of their collaboration on the cognitive and communicative level. More specifically, the correlation of collaborative learners'…

The Food Peddlers. Nutrition Comes Alive. Level 3. Nutrition Educator's Guide and Work Sheets, Letters to Parents, Recipes. Revised Edition.

ERIC Educational Resources Information Center

Mapes, Martha C.; Thonney, Patricia

This guide provides a nutrition education program for elementary school students that spans kindergarten through Grade 3 as well as providing activities for specific levels. Nutrition education objectives are stated for each grade level: (1) kindergarten--students will become familiar with and motivated to eat a variety of foods; (2) grade…

An object-oriented software approach for a distributed human tracking motion system

NASA Astrophysics Data System (ADS)

Micucci, Daniela L.

2003-06-01

Tracking is a composite job involving the co-operation of autonomous activities which exploit a complex information model and rely on a distributed architecture. Both information and activities must be classified and related in several dimensions: abstraction levels (what is modelled and how information is processed); topology (where the modelled entities are); time (when entities exist); strategy (why something happens); responsibilities (who is in charge of processing the information). A proper Object-Oriented analysis and design approach leads to a modular architecture where information about conceptual entities is modelled at each abstraction level via classes and intra-level associations, whereas inter-level associations between classes model the abstraction process. Both information and computation are partitioned according to level-specific topological models. They are also placed in a temporal framework modelled by suitable abstractions. Domain-specific strategies control the execution of the computations. Computational components perform both intra-level processing and intra-level information conversion. The paper overviews the phases of the analysis and design process, presents major concepts at each abstraction level, and shows how the resulting design turns into a modular, flexible and adaptive architecture. Finally, the paper sketches how the conceptual architecture can be deployed into a concrete distribute architecture by relying on an experimental framework.

Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest.

PubMed

Purahong, Witoon; Durka, Walter; Fischer, Markus; Dommert, Sven; Schöps, Ricardo; Buscot, François; Wubet, Tesfaye

2016-11-18

Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicochemical properties, on the overall and specific soil enzyme activity patterns. Our results indicate that tree species identity, tree genotypes and genotypic diversity level have significant influences on overall and specific soil enzyme activity patterns. These three factors influence soil enzyme patterns partly through effects on soil physicochemical properties and substrate quality. Variance partitioning showed that tree species identity, genotypic diversity level, pH and water content all together explained ~30% variations in the overall patterns of soil enzymes. However, we also found that the responses of soil ecosystem functions to tree genotypes and genotypic diversity are complex, being dependent on tree species identity and controlled by multiple factors. Our study highlights the important of inter- and intra-specific variations in tree species in shaping soil ecosystem functions in a subtropical forest.

Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest

PubMed Central

Purahong, Witoon; Durka, Walter; Fischer, Markus; Dommert, Sven; Schöps, Ricardo; Buscot, François; Wubet, Tesfaye

2016-01-01

Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicochemical properties, on the overall and specific soil enzyme activity patterns. Our results indicate that tree species identity, tree genotypes and genotypic diversity level have significant influences on overall and specific soil enzyme activity patterns. These three factors influence soil enzyme patterns partly through effects on soil physicochemical properties and substrate quality. Variance partitioning showed that tree species identity, genotypic diversity level, pH and water content all together explained ~30% variations in the overall patterns of soil enzymes. However, we also found that the responses of soil ecosystem functions to tree genotypes and genotypic diversity are complex, being dependent on tree species identity and controlled by multiple factors. Our study highlights the important of inter- and intra-specific variations in tree species in shaping soil ecosystem functions in a subtropical forest. PMID:27857198

The relationship between self-efficacy for behaviors that promote healthy weight and clinical indicators of adiposity in a sample of early adolescents.

PubMed

Steele, Michael M; Daratha, Kenn B; Bindler, Ruth C; Power, Thomas G

2011-12-01

Examine the relationship between self-efficacy and various measures of adiposity in a sample of teens. A total of 132 teens were selected from schools participating in an existing research study titled Teen Eating and Activity Mentoring in Schools (TEAMS). Teens completed demographic questionnaires and healthy eating-specific and physical activity-specific measures of self-efficacy. Waist circumference (WC), triceps skinfold thickness (TSF), and body mass index (BMI) percentile scores were also obtained. Regression analyses indicated that healthy eating-specific and physical activity-specific measures of self-efficacy predicted WC and TSF. ANOVA revealed significant differences in healthy eating-specific self-efficacy levels between students of recommended weight and overweight/obese status. Supplemental analyses showed significant negative relationships between a student's ideal BMI ratio and self-efficacy. Because self-efficacy may be amenable to change, these findings could inform future efforts aimed at increasing behaviors that promote healthy weight status among early adolescents.

Use Level and Encounters: Important Variables of Perceived Crowding Among Nonspecialized Recreationists.

ERIC Educational Resources Information Center

Hammitt, William E.; And Others

1984-01-01

Use level, visual encounters, crowding expectations, and feelings were examined by regression techniques to explain perceived crowding among innertube floaters. Degree of user specialization and specificity for any given activity and place is offered as an explanation for the discrepancy from previous findings. (Author/DF)

18 CFR 725.3 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... result in the long- or short-term adverse impacts associated with: (a) The occupancy or modification of... apply to Level A and B regional or river basin planning activities carried out by regional planning sponsors including consideration of inclusion of site specific projects in Level A or B regional or river...

18 CFR 725.3 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... result in the long- or short-term adverse impacts associated with: (a) The occupancy or modification of... apply to Level A and B regional or river basin planning activities carried out by regional planning sponsors including consideration of inclusion of site specific projects in Level A or B regional or river...

18 CFR 725.3 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... result in the long- or short-term adverse impacts associated with: (a) The occupancy or modification of... apply to Level A and B regional or river basin planning activities carried out by regional planning sponsors including consideration of inclusion of site specific projects in Level A or B regional or river...

Face adaptation aftereffects reveal anterior medial temporal cortex role in high level category representation.

PubMed

Furl, N; van Rijsbergen, N J; Treves, A; Dolan, R J

2007-08-01

Previous studies have shown reductions of the functional magnetic resonance imaging (fMRI) signal in response to repetition of specific visual stimuli. We examined how adaptation affects the neural responses associated with categorization behavior, using face adaptation aftereffects. Adaptation to a given facial category biases categorization towards non-adapted facial categories in response to presentation of ambiguous morphs. We explored a hypothesis, posed by recent psychophysical studies, that these adaptation-induced categorizations are mediated by activity in relatively advanced stages within the occipitotemporal visual processing stream. Replicating these studies, we find that adaptation to a facial expression heightens perception of non-adapted expressions. Using comparable behavioral methods, we also show that adaptation to a specific identity heightens perception of a second identity in morph faces. We show both expression and identity effects to be associated with heightened anterior medial temporal lobe activity, specifically when perceiving the non-adapted category. These regions, incorporating bilateral anterior ventral rhinal cortices, perirhinal cortex and left anterior hippocampus are regions previously implicated in high-level visual perception. These categorization effects were not evident in fusiform or occipital gyri, although activity in these regions was reduced to repeated faces. The findings suggest that adaptation-induced perception is mediated by activity in regions downstream to those showing reductions due to stimulus repetition.

Cellular and Molecular Pathways Leading to External Root Resorption

PubMed Central

Iglesias-Linares, A.; Hartsfield, J.K.

2016-01-01

External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68+, iNOS+ M1- and CD68+, CD163+ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels. PMID:27811065

Bicentennial Source Book, Level I, K-2.

ERIC Educational Resources Information Center

Herb, Sharon; And Others

This student activities source book is one of a series of four developed by the Carroll County Public School System, Maryland, for celebration of the Bicentennial. It is specifically designed to generate ideas integrating the Bicentennial celebration into various disciplines, classroom activities, and school-wide events at the kindergarten through…

Bicentennial Source Book, Level II, Grades 3-5.

ERIC Educational Resources Information Center

Orth, Nancy; And Others

This study activities source book is one of a series of four developed by the Carroll County Public School System, Maryland, for celebration of the Bicentennial. It is specifically designed to generate ideas integrating the Bicentennial celebration into various disciplines, classroom activities, and school-wide events at the third grade through…

Gender-specific automatic valence recognition of affective olfactory stimulation through the analysis of the electrodermal activity.

PubMed

Greco, Alberto; Lanata, Antonio; Valenza, Gaetano; Di Francesco, Fabio; Scilingo, Enzo Pasquale

2016-08-01

This study reports on the development of a gender-specific classification system able to discern between two valence levels of smell, through information gathered from electrodermal activity (EDA) dynamics. Specifically, two odorants were administered to 32 healthy volunteers (16 males) while monitoring EDA. CvxEDA model was used to process the EDA signal and extract features from both tonic and phasic components. The feature set was used as input to a K-NN classifier implementing a leave-one-subject-out procedure. Results show strong differences in the accuracy of valence recognition between men (62.5%) and women (78%). We can conclude that affective olfactory stimulation significantly affect EDA dynamics with a highly specific gender dependency.

Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

EPA Science Inventory

The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

Does the Neighborhood Context Alter the Link between Youth's After-School Time Activities and Developmental Outcomes? A Multilevel Analysis

ERIC Educational Resources Information Center

Fauth, Rebecca C.; Roth, Jodie L.; Brooks-Gunn, Jeanne

2007-01-01

This article examines links between different measures of after-school time activity participation (5 specific activities and breadth) on youth's developmental outcomes (anxiety/depression, delinquency, and substance use) over 6 years and whether these links are moderated by neighborhood-level variables. The sample (N = 1,315) of 9- and…

Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc)

EPA Science Inventory

The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

Self-reported domain-specific and accelerometer-based physical activity and sedentary behaviour in relation to psychological distress among an urban Asian population.

PubMed

Chu, A H Y; van Dam, R M; Biddle, S J H; Tan, C S; Koh, D; Müller-Riemenschneider, F

2018-04-05

The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population. From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics. The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18). Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.

(14)C levels in the vicinity of the Fukushima Dai-ichi Nuclear Power Plant prior to the 2011 accident.

PubMed

Xu, Sheng; Cook, Gordon T; Cresswell, Alan J; Dunbar, Elaine; Freeman, Stewart P H T; Hastie, Helen; Hou, Xiaolin; Jacobsson, Piotr; Naysmith, Philip; Sanderson, David C W; Tripney, Brian G; Yamaguchi, Katsuhiko

2016-06-01

A 50-year-old Japanese cedar (Cryptomeria japonica) from Okuma, ∼1 km southwest of the Fukushima Dai-ichi Nuclear Power Plant, was cored and each annual ring was analysed for (14)C. The (14)C specific activity values varied from 330.4 Bq kg(-1) C in the tree ring formed in 1971 to 231.2 Bq kg(-1) C in the 2014 ring. During the periods 1971-1976 and 2011-2014, the (14)C specific activities are indistinguishable from the ambient background values. However, compared with the ambient atmospheric levels, the (14)C specific activities between 1977 and 2010 are significantly elevated, clearly indicating (14)C discharges from the reactors during their normal operations. In addition, the specific activities are positively correlated with the annual electricity generation values. The excess (14)C specific activities were <36 Bq kg(-1) C, corresponding to an additional annual effective dose of <2 μSv via the food ingestion pathway in the study location. The primary wind direction is east-southeast/southeast with a frequency of ∼30%, in comparison to ∼20% frequency for the direction of the site under study (north-northeast/northeast). This would tend to indicate a similar magnitude of additional effective dose and consequently no significant radiological impact of atmospheric (14)C discharges from the FDNPP during the entire period of normal operations. Additionally, no (14)C pulse in activity can be observed in the year 2011 ring. This might be caused by a limited (14)C release from the damaged reactors during the accident or that the prevailing wind during the short period of release (11th-25th March 2011) was not in the direction of Okuma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using TENS for pain control: the state of the evidence

PubMed Central

Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

2014-01-01

Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells.

PubMed

Damiano, Sara; Montagnaro, Serena; Puzio, Maria V; Severino, Lorella; Pagnini, Ugo; Barbarino, Marcella; Cesari, Daniele; Giordano, Antonio; Florio, Salvatore; Ciarcia, Roberto

2018-06-01

In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study, we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation, and apoptosis. To test the possible mechanisms of action of such antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, δ-TOCO, and NAC, at dose used, significantly reduced the intracellular levels of MDA induced by DAS or NIL; 2) RES, rMnSOD, and δ-TOCO increased the intracellular ROS levels; 3) The increase ROS levels is related to higher levels of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced this activity. Interestingly, our data showed that apoptotic activity of DAS and NIL have significantly increased the production of oligonucleosomes by triggering excessive ROS generation as well as functionality of SERCA receptors. © 2018 Wiley Periodicals, Inc.

Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

PubMed

Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

2016-02-01

Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis. © 2015 John Wiley & Sons Ltd.

Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross-sectional study on effects of time since injury and physical activity level.

PubMed

de Groot, Sonja; van der Scheer, Jan W; Bakkum, Arjan J T; Adriaansen, Jacinthe J E; Smit, Christof A; Dijkstra, Catja; Post, Marcel W M; van der Woude, Lucas H V

2016-01-01

To study the impact of time since injury (TSI) and physical activity (PA) on fitness of persons with spinal cord injury (SCI). Cross-sectional study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and ≥30 years after SCI and divided in an active and inactive group. Fitness [peak power output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. In persons with tetraplegia, no significant relationship was found between TSI and fitness after controlling for confounders, while a higher activity level was related to a higher POpeak in this group. Active people with tetraplegia also showed less decline in POpeak with an increase in TSI compared to inactive people. In persons with paraplegia, after controlling for confounders, it was shown that TSI had a negative effect on POpeak, while PA was not significantly associated with fitness in people with paraplegia. In people with paraplegia, fitness was significantly lower in those with a longer TSI. Persons with a long TSI might need more attention to remain fit and PA might be an important element in that respect as shown by the results of the group with a tetraplegia. Wheelchair-specific fitness seems to diminish over time after paraplegia. An active lifestyle is related to wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term deconditioning is very important.

Mechanical stimulation of skeletal muscle generates lipid-related second messengers by phospholipase activation

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.; Shansky, J.; Karlisch, P.; Solerssi, R. L.

1993-01-01

Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins (PG) E2 and F2 alpha which regulate protein turnover rates and muscle cell growth. These stretch-induced PG increases are reduced in low extracellular calcium medium and by specific phospholipase inhibitors. Mechanical stimulation increases the breakdown rate of 3H-arachidonic acid labelled phospholipids, releasing free 3H-arachidonic acid, the rate-limiting precursor of PG synthesis. Mechanical stimulation also increases 3H-arachidonic acid labelled diacylglycerol formation and intracellular levels of inositol phosphates from myo-[2-3H]inositol labelled phospholipids. Phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PLC), and phospholipase D (PLD) are all activated by stretch. The stretch-induced increases in PG production, 3H-arachidonic acid labelled phospholipid breakdown, and 3H-arachidonic acid labelled diacylglycerol formation occur independently of cellular electrical activity (tetrodotoxin insensitive) whereas the formation of inositol phosphates from myo-[2-3H]inositol labelled phospholipids is dependent on cellular electrical activity. These results indicate that mechanical stimulation increases the lipid-related second messengers arachidonic acid, diacylglycerol, and PG through activation of specific phospholipases such as PLA2 and PLD, but not by activation of phosphatidylinositol-specific PLC.

Physical education resources, class management, and student physical activity levels: a structure-process-outcome approach to evaluating physical education effectiveness.

PubMed

Bevans, Katherine B; Fitzpatrick, Leslie-Anne; Sanchez, Betty M; Riley, Anne W; Forrest, Christopher

2010-12-01

This study was conducted to empirically evaluate specific human, curricular, and material resources that maximize student opportunities for physical activity during physical education (PE) class time. A structure-process-outcome model was proposed to identify the resources that influence the frequency of PE and intensity of physical activity during PE. The proportion of class time devoted to management was evaluated as a potential mediator of the relations between resource availability and student activity levels. Data for this cross-sectional study were collected from interviews conducted with 46 physical educators and the systematic observation of 184 PE sessions in 34 schools. Regression analyses were conducted to test for the main effects of resource availability and the mediating role of class management. Students who attended schools with a low student-to-physical educator ratio had more PE time and engaged in higher levels of physical activity during class time. Access to adequate PE equipment and facilities was positively associated with student activity levels. The availability of a greater number of physical educators per student was found to impact student activity levels by reducing the amount of session time devoted to class management. The identification of structure and process predictors of student activity levels in PE will support the allocation of resources and encourage instructional practices that best support increased student activity levels in the most cost-effective way possible. Implications for PE policies and programs are discussed. © 2010, American School Health Association.

Perceived correlates of domain-specific physical activity in rural adults in the Midwest.

PubMed

Chrisman, Matthew; Nothwehr, Faryle; Yang, Jingzen; Oleson, Jacob

2014-01-01

In response to calls for more specificity when measuring physical activity, this study examined perceived correlates of this behavior in rural adults separately by the domain in which this behavior occurs (ie, home care, work, active living, and sport). A cross-sectional survey was completed by 407 adults from 2 rural towns in the Midwest. The questionnaire assessed the perceived social and physical environment, including neighborhood characteristics, as well as barriers to being active. The Kaiser Physical Activity Survey captured domain-specific activity levels. The response rate was 25%. Multiple regression analyses were conducted to examine the associations between social and physical environment factors and domain-specific physical activity. Having a favorable attitude toward using government funds for exercise and activity-friendly neighborhood characteristic were positively associated with active living. Friends encouraging exercise was positively associated with participation in sport. Barriers were inversely associated with active living and sport. Total physical activity was positively associated with workplace incentives for exercise, favorable policy attitudes toward supporting physical education in schools and supporting the use of government funds for biking trails, and it was inversely associated with barriers. There were no factors associated with physical activity in the domains of work or home care. Correlates of physical activity are unique to the domain in which this behavior occurs. Programs to increase physical activity in rural adults should target policy attitudes, neighborhood characteristics, and social support from friends while also working to decrease personal barriers to exercise. © 2014 National Rural Health Association.

Trigger values for investigation of hormonal activity in drinking water and its sources using CALUX bioassays.

PubMed

Brand, Walter; de Jongh, Cindy M; van der Linden, Sander C; Mennes, Wim; Puijker, Leo M; van Leeuwen, Cornelis J; van Wezel, Annemarie P; Schriks, Merijn; Heringa, Minne B

2013-05-01

To screen for hormonal activity in water samples, highly sensitive in vitro CALUX bioassays are available which allow detection of estrogenic (ERα), androgenic (AR), progestagenic (PR), and glucocorticoid (GR) activities. This paper presents trigger values for the ERα, AR, PR, and GR CALUX bioassays for agonistic hormonal activities in (drinking) water, which define a level above which human health risk cannot be waived a priori and additional examination of specific endocrine activity may be warranted. The trigger values are based on 1) acceptable or tolerable daily intake (ADI/TDI) values of specific compounds, 2) pharmacokinetic factors defining their bioavailability, 3) estimations of the bioavailability of unknown compounds with equivalent hormonal activity, 4) relative endocrine potencies, and 5) physiological, and drinking water allocation factors. As a result, trigger values of 3.8ng 17β-estradiol (E2)-equivalents (eq)/L, 11ng dihydrotestosterone (DHT)-eq/L, 21ng dexamethasone (DEX)-eq/L, and 333ng Org2058-eq/L were derived. Benchmark Quotient (BQ) values were derived by dividing hormonal activity in water samples by the derived trigger using the highest concentrations detected in a recent, limited screening of Dutch water samples, and were in the order of (value) AR (0.41)>ERα (0.13)>GR (0.06)>PR (0.04). The application of trigger values derived in the present study can help to judge measured agonistic hormonal activities in water samples using the CALUX bioassays and help to decide whether further examination of specific endocrine activity followed by a subsequent safety evaluation may be warranted, or whether concentrations of such activity are of low priority with respect to health concerns in the human population. For instance, at one specific drinking water production site ERα and AR (but no GR and PR) activities were detected in drinking water, however, these levels are at least a factor 83 smaller than the respective trigger values, and therefore no human health risks are to be expected from hormonal activity in Dutch drinking water from this site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Variable interaction specificity and symbiont performance in Panamanian Trachymyrmex and Sericomyrmex fungus-growing ants.

PubMed

De Fine Licht, Henrik H; Boomsma, Jacobus J

2014-12-04

Cooperative benefits of mutualistic interactions are affected by genetic variation among the interacting partners, which may have consequences for interaction-specificities across guilds of sympatric species with similar mutualistic life histories. The gardens of fungus-growing (attine) ants produce carbohydrate active enzymes that degrade plant material collected by the ants and offer them food in exchange. The spectrum of these enzyme activities is an important symbiont service to the host but may vary among cultivar genotypes. The sympatric occurrence of several Trachymyrmex and Sericomyrmex higher attine ants in Gamboa, Panama provided the opportunity to do a quantitative study of species-level interaction-specificity. We genotyped the ants for Cytochrome Oxidase and their Leucoagaricus fungal cultivars for ITS rDNA. Combined with activity measurements for 12 carbohydrate active enzymes, these data allowed us to test whether garden enzyme activity was affected by fungal strain, farming ants or combinations of the two. We detected two cryptic ant species, raising ant species number from four to six, and we show that the 38 sampled colonies reared a total of seven fungal haplotypes that were different enough to represent separate Leucoagaricus species. The Sericomyrmex species and one of the Trachymyrmex species reared the same fungal cultivar in all sampled colonies, but the remaining four Trachymyrmex species largely shared the other cultivars. Fungal enzyme activity spectra were significantly affected by both cultivar species and farming ant species, and more so for certain ant-cultivar combinations than others. However, relative changes in activity of single enzymes only depended on cultivar genotype and not on the ant species farming a cultivar. Ant cultivar symbiont-specificity varied from almost full symbiont sharing to one-to-one specialization, suggesting that trade-offs between enzyme activity spectra and life-history traits such as desiccation tolerance, disease susceptibility and temperature sensitivity may apply in some combinations but not in others. We hypothesize that this may be related to ecological specialization in general, but this awaits further testing. Our finding of both cryptic ant species and extensive cultivar diversity underlines the importance of identifying all species-level variation before embarking on estimates of interaction specificity.

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

PubMed

Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

2018-03-28

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

Reducing Societal Obesity: Establishing a Separate Exercise Model through Studies of Group Behavior.

PubMed

Puterbaugh, J S

2016-01-01

The past 50 years has brought attention to high and increasing levels of human obesity in most of the industrialized world. The medical profession has noticed, has evaluated, and has developed models for studying, preventing, and reversing obesity. The current model prescribes activity in specific quantities such as days, minutes, heart rates, and footfalls. Although decreased levels of activity have come from changes revolving around built environments and social networks, the existing medical model to lower body weights by increasing activity remains individually prescriptive. It is not working. The study of societal obesity precludes the individual and must involve group behavioral studies. Such studies necessitate acquiring separate tools and, therefore, require a significant change in the evaluation and treatment of obesity. Finding groups with common activities and lower levels of obesity would allow the development of new models of land use and encourage active lifestyles through shared interests.

Physical Activity and Its Correlates among Adults in Malaysia: A Cross-Sectional Descriptive Study.

PubMed

Cai Lian, Tam; Bonn, Gregory; Si Han, Yeoh; Chin Choo, Yap; Chee Piau, Wong

2016-01-01

Obesity and rates of non-communicable diseases linked to physical inactivity have increased dramatically in Malaysia over the past 20 years. Malaysia has also been identified as one of the least physically active countries in the world with over 60% of adults being essentially sedentary. This study examines the relationship of socio-demographic factors to physical activity among 770 adults from 3 Malaysian states. Physical activity levels were significantly related to ethnicity, gender, age, occupation and educational level. Controlling for inter-relationships among these variables; age, gender, Chinese ethnicity and education level were found to have unique effects on total physical activity, as well as moderate and vigorous exercise. As would be expected, younger people were more physically active, engaging more in both moderate and vigorous types of exercise and males were generally more active than females. Contrary to findings from many developed countries, however, more educated Malaysians were less likely to engage in all types of physical activity. Ethnic Chinese participants, and to a lesser degree Indians also consistently reported lower levels of activity. Possible intervention strategies are discussed that specifically target ethnic and cultural norms related to physical activity. Future research programs exploring barriers to participation and perceptions of physical activity, as well as programs to encourage active life styles among youths are also suggested.

Posttranslational elevation of cell wall invertase activity by silencing its inhibitor in tomato delays leaf senescence and increases seed weight and fruit hexose level.

PubMed

Jin, Ye; Ni, Di-An; Ruan, Yong-Ling

2009-07-01

Invertase plays multiple pivotal roles in plant development. Thus, its activity must be tightly regulated in vivo. Emerging evidence suggests that a group of small proteins that inhibit invertase activity in vitro appears to exist in a wide variety of plants. However, little is known regarding their roles in planta. Here, we examined the function of INVINH1, a putative invertase inhibitor, in tomato (Solanum lycopersicum). Expression of a INVINH1:green fluorescent protein fusion revealed its apoplasmic localization. Ectopic overexpression of INVINH1 in Arabidopsis thaliana specifically reduced cell wall invertase activity. By contrast, silencing its expression in tomato significantly increased the activity of cell wall invertase without altering activities of cytoplasmic and vacuolar invertases. Elevation of cell wall invertase activity in RNA interference transgenic tomato led to (1) a prolonged leaf life span involving in a blockage of abscisic acid-induced senescence and (2) an increase in seed weight and fruit hexose level, which is likely achieved through enhanced sucrose hydrolysis in the apoplasm of the fruit vasculature. This assertion is based on (1) coexpression of INVINH1 and a fruit-specific cell wall invertase Lin5 in phloem parenchyma cells of young fruit, including the placenta regions connecting developing seeds; (2) a physical interaction between INVINH1 and Lin5 in vivo; and (3) a symplasmic discontinuity at the interface between placenta and seeds. Together, the results demonstrate that INVINH1 encodes a protein that specifically inhibits the activity of cell wall invertase and regulates leaf senescence and seed and fruit development in tomato by limiting the invertase activity in planta.

An examination of quality of care in Norwegian nursing homes - a change to more activities?

PubMed

Kjøs, Bente Ø; Havig, Anders K

2016-06-01

Studies on Norwegian nursing homes have shown that the general care is at a relatively high level, while the level of physical and social activities is relatively low. As a response to these findings, the Norwegian government has stressed the importance of activities in various white papers and circulars and, in recent years, has launched several campaigns specifically aimed at increasing the level of activities. The aim of the study was to examine the following: (i) how the government has succeeded in increasing the level of physical and social activities in Norwegian nursing homes; (ii) how the level of activities compares to the general care; and (iii) how the level of activities and the general care are influenced by the following facility characteristics: residents' mobility level, total staffing levels, ratio of RNs, ratio of unlicensed staff and ward size. A cross-sectional survey of forty nursing home wards throughout Norway was used to collect the data. On a scale ranging from 1 to 7, the staff members assess the activity dimension to be 4.31 and the general care dimension to be 5.66. The activity dimension was significantly negatively correlated with the ratio of unlicensed staff, the ratio of Registered Nurses and the residents' mobility level, while the general care dimension was significantly negatively correlated with the ratio of unlicensed staff. The study shows that the level of physical and social activities offered to the residents is relatively low, while the general care level is significantly higher, in line with earlier studies. Consequently, the government has not succeeded with its current policy to increase the level of activities in nursing homes. The relationship between the two quality dimensions and the explanatory variables shows that nursing home quality is a complicated phenomenon. © 2015 Nordic College of Caring Science.

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

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

Coping Skills Are Associated With Gastrointestinal Symptom Severity and Somatization in Patients With Irritable Bowel Syndrome.

PubMed

Wilpart, Katarina; Törnblom, Hans; Svedlund, Jan; Tack, Jan F; Simrén, Magnus; Van Oudenhove, Lukas

2017-10-01

Coping resources and processes are altered in patients with irritable bowel syndrome (IBS). We investigated the relationship between coping resources and gastrointestinal (GI) and extraintestinal symptom severity in patients with IBS and potential mediators of this relationship. We performed a cross-sectional study of 216 patients with IBS attending a secondary/tertiary care specialized outpatient center in Sweden from 2003 through 2007. We collected data on coping resources, levels of anxiety (general and GI specific), depressive symptoms, levels of GI symptoms, and extraintestinal somatic symptoms (somatization) by administering validated self-report questionnaires. General Linear Models were used to assess associations and mediation. GI symptoms: low levels of physical coping resources (practice of activities that are beneficial for health; P = .0016), high levels of general anxiety symptoms (P = .033), and GI-specific anxiety symptoms (P < .0001), but not depressive symptoms (P = .89), were independently associated with GI symptom levels (R 2  = 0.31). Anxiety and GI-specific anxiety partially mediated the effect of physical coping. Somatization: low levels of physical coping resources (P = .003), high levels of anxiety (P = .0147), depressive (P = .0005), and GI-specific anxiety symptoms (P = .06) were associated with somatization levels (R 2  = 0.35). Levels of general and GI-specific anxiety and depressive symptoms partially mediated this physical coping effect. The effect of psychological coping resources (including optimism, social support, and accepting/expressing emotions) on somatization levels was not significant (P = .98), but was fully mediated by levels of anxiety and depressive symptoms, and partially by levels of GI-specific anxiety symptoms. In a cross-sectional study of patients with IBS in Sweden, we found associations of levels of coping resources with GI and extraintestinal symptom severity; these associations were mediated by levels of anxiety and depressive symptoms. Although confirmation in longitudinal studies is needed, this identifies coping as a potential psychological treatment target in IBS. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

PubMed

Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

2016-06-01

Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Proximity to sports facilities and sports participation for adolescents in Germany.

PubMed

Reimers, Anne K; Wagner, Matthias; Alvanides, Seraphim; Steinmayr, Andreas; Reiner, Miriam; Schmidt, Steffen; Woll, Alexander

2014-01-01

To assess the relationship between proximity to specific sports facilities and participation in the corresponding sports activities for adolescents in Germany. A sample of 1,768 adolescents aged 11-17 years old and living in 161 German communities was examined. Distances to the nearest sports facilities were calculated as an indicator of proximity to sports facilities using Geographic Information Systems (GIS). Participation in specific leisure-time sports activities in sports clubs was assessed using a self-report questionnaire and individual-level socio-demographic variables were derived from a parent questionnaire. Community-level socio-demographics as covariates were selected from the INKAR database, in particular from indicators and maps on land development. Logistic regression analyses were conducted to examine associations between proximity to the nearest sports facilities and participation in the corresponding sports activities. The logistic regression analyses showed that girls residing longer distances from the nearest gym were less likely to engage in indoor sports activities; a significant interaction between distances to gyms and level of urbanization was identified. Decomposition of the interaction term showed that for adolescent girls living in rural areas participation in indoor sports activities was positively associated with gym proximity. Proximity to tennis courts and indoor pools was not associated with participation in tennis or water sports, respectively. Improved proximity to gyms is likely to be more important for female adolescents living in rural areas.

Proximity to Sports Facilities and Sports Participation for Adolescents in Germany

PubMed Central

Reimers, Anne K.; Wagner, Matthias; Alvanides, Seraphim; Steinmayr, Andreas; Reiner, Miriam; Schmidt, Steffen; Woll, Alexander

2014-01-01

Objectives To assess the relationship between proximity to specific sports facilities and participation in the corresponding sports activities for adolescents in Germany. Methods A sample of 1,768 adolescents aged 11–17 years old and living in 161 German communities was examined. Distances to the nearest sports facilities were calculated as an indicator of proximity to sports facilities using Geographic Information Systems (GIS). Participation in specific leisure-time sports activities in sports clubs was assessed using a self-report questionnaire and individual-level socio-demographic variables were derived from a parent questionnaire. Community-level socio-demographics as covariates were selected from the INKAR database, in particular from indicators and maps on land development. Logistic regression analyses were conducted to examine associations between proximity to the nearest sports facilities and participation in the corresponding sports activities. Results The logisitic regression analyses showed that girls residing longer distances from the nearest gym were less likely to engage in indoor sports activities; a significant interaction between distances to gyms and level of urbanization was identified. Decomposition of the interaction term showed that for adolescent girls living in rural areas participation in indoor sports activities was positively associated with gym proximity. Proximity to tennis courts and indoor pools was not associated with participation in tennis or water sports, respectively. Conclusions Improved proximity to gyms is likely to be more important for female adolescents living in rural areas. PMID:24675689

The Hip Sports Activity Scale (HSAS) for patients with femoroacetabular impingement.

PubMed

Naal, Florian D; Miozzari, Hermes H; Kelly, Bryan T; Magennis, Erin M; Leunig, Michael; Noetzli, Hubert P

2013-01-01

To develop and validate a sports activity scale for patients with a diagnosis of femoroacetabular impingement (FAI).
 A nine level Hip Sports Activity Scale (HSAS) was constructed both in German and English languages. Fifty-nine consecutive patients undergoing surgical treatment for FAI at two centers in Switzerland and in the US completed a questionnaire set consisting of the HSAS, the University of California at Los Angeles (UCLA) activity scale and different hip joint-specific and generic outcome tools. For reliability assessment, the HSAS was completed twice about nine days apart. Evidence of reliability, validity and responsiveness was investigated by classical psychometric analyses.
 Reliability was excellent for both the German and the English versions with intraclass correlation coefficients of 0.94 and 0.96, respectively. Evidence of convergent validity was supported by moderate to high correlations with the UCLA activity scale and with the joint-specific measures used. Evidence of divergent validity was supported by low correlations with the SF-12 Mental Component Scale and the WOMAC stiffness subscale. The standardised response mean was 0.69.
 The HSAS is a reliable and valid tool to determine sports levels in patients suffering from FAI. Its use in future studies investigating outcomes in young patients with hip disease can be recommended.
 Level III, Diagnostic Studies - An independent, masked comparison with an appropriate population of patients, but reference standard not applied to all study patients.

Pathophysiology and principles of management of the many faces of the acute vaso-occlusive crisis in patients with sickle cell disease.

PubMed

Ballas, Samir K

2015-08-01

Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Adenosine Deaminase activity and HLA-DRB as diagnostic markers for Rheumatoid Arthritis.

PubMed

Valadbeigi, Shirin; Ebrahimi-Rad, Mina; Khatami, Shohreh; Akhbari, Hadi; Saghiri, Reza

2018-04-05

Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine deaminase (ADA) isoenzymes could be useful and specific. The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases. Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive protein (CRP), rheumatoid factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*1,*04 and *010 was detected using PCR-SSP. ADA activity, particularly ADA2 level, was significantly higher among RA group (P<0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (P <0.05). The allele prevalence of DRB1*10 and *01 was significantly higher in RA patients (8.3% and 13.1%, respectively) compared with control group (2.51% and 5.5%, respectively) (P <0.05). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively. Increase tADA level and the frequency of DRB1*010 and *01 caused to susceptibility to RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rapid regulation of brain-derived neurotrophic factor mRNA within eye-specific circuits during ocular dominance column formation.

PubMed

Lein, E S; Shatz, C J

2000-02-15

The neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as a candidate retrograde signaling molecule for geniculocortical axons during the formation of ocular dominance columns. Here we examined whether neuronal activity can regulate BDNF mRNA in eye-specific circuits in the developing cat visual system. Dark-rearing throughout the critical period for ocular dominance column formation decreases levels of BDNF mRNA within primary visual cortex, whereas short-term (2 d) binocular blockade of retinal activity with tetrodotoxin (TTX) downregulates BDNF mRNA within the lateral geniculate nucleus (LGN) and visual cortical areas. Brief (6 hr to 2 d) monocular TTX blockade during the critical period and also in adulthood causes downregulation in appropriate eye-specific laminae in the LGN and ocular dominance columns within primary visual cortex. Monocular TTX blockade at postnatal day 23 also downregulates BDNF mRNA in a periodic fashion, consistent with recent observations that ocular dominance columns can be detected at these early ages by physiological methods. In contrast, 10 d monocular TTX during the critical period does not cause a lasting decrease in BDNF mRNA expression in columns pertaining to the treated eye, consistent with the nearly complete shift in physiological response properties of cortical neurons in favor of the unmanipulated eye known to result from long-term monocular deprivation. These observations demonstrate that BDNF mRNA levels can provide an accurate "molecular readout" of the activity levels of cortical neurons and are consistent with a highly local action of BDNF in strengthening and maintaining active synapses during ocular dominance column formation.

Task-specific reorganization of the auditory cortex in deaf humans

PubMed Central

Bola, Łukasz; Zimmermann, Maria; Mostowski, Piotr; Jednoróg, Katarzyna; Marchewka, Artur; Rutkowski, Paweł; Szwed, Marcin

2017-01-01

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior–lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain. PMID:28069964

Task-specific reorganization of the auditory cortex in deaf humans.

PubMed

Bola, Łukasz; Zimmermann, Maria; Mostowski, Piotr; Jednoróg, Katarzyna; Marchewka, Artur; Rutkowski, Paweł; Szwed, Marcin

2017-01-24

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior-lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain.

The Little Six Personality Dimensions From Early Childhood to Early Adulthood: Mean-Level Age and Gender Differences in Parents' Reports.

PubMed

Soto, Christopher J

2016-08-01

The present research pursues three major goals. First, we develop scales to measure the Little Six youth personality dimensions: Extraversion, Agreeableness, Conscientiousness, Neuroticism, Openness to Experience, and Activity. Second, we examine mean-level age and gender differences in the Little Six from early childhood into early adulthood. Third, we examine the development of more specific nuance traits. We analyze parent reports, made using the common-language California Child Q-Set (CCQ), for a cross-sectional sample of 16,000 target children ranging from 3 to 20 years old. We construct CCQ-Little Six scales that reliably measure each Little Six dimension. Using these scales, we find (a) curvilinear, U-shaped age trends for Agreeableness, Conscientiousness, and Openness, with declines followed by subsequent inclines; (b) monotonic, negative age trends for Extraversion and Activity; (c) higher levels of Conscientiousness and Agreeableness among girls than boys, as well as higher levels of Activity among boys than girls; and (d) gender-specific age trends for Neuroticism, with girls scoring higher than boys by mid-adolescence. Finally, we find that several nuance traits show distinctive developmental trends that differ from their superordinate Little Six dimension. These results highlight childhood and adolescence as key periods of personality development. © 2015 Wiley Periodicals, Inc.

Cystamine restores GSTA3 levels in Vanin-1 null mice.

PubMed

Di Leandro, Luana; Maras, Bruno; Schininà, M Eugenia; Dupré, Silvestro; Koutris, Ilias; Martin, Florent M; Naquet, Philippe; Galland, Franck; Pitari, Giuseppina

2008-03-15

Free cysteamine levels in mouse tissues have been strictly correlated to the presence of membrane-bound pantetheinase activity encoded by Vanin-1. Vanin-1 is involved in many biological processes in mouse, from thymus homing to sexual development. Vanin-1 -/- mice are fertile and grow and develop normally; they better control inflammation and most of the knockout effects were rescued by cystamine treatment. Gene structure analysis showed the presence of an oxidative stimuli-responsive ARE-like sequence in the promoter. In this paper we investigate antioxidant-detoxifying enzymatic activities at the tissue level, comparing Vanin-1 -/- and wild-type mice. In Vanin-1 null animals we pointed out a decrease in the Se-independent glutathione peroxidase activity. The decrease in enzymatic activity appeared to be correlated to an impairment of GST isoenzyme levels. In particular a significant drop in GSTA3 together with a minor decrement in GSTM1 and an increase in GSTP1 levels was detected in Vanin-1 -/- livers. Cystamine administration to Vanin-1 -/- mice restored specifically GSTA3 levels and the corresponding enzymatic activity without influencing protein expression. A possible role of cystamine on protein stability/folding can be postulated.

/sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

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

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormalmore » /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.« less

Language-Invariant Verb Processing Regions in Spanish-English Bilinguals

PubMed Central

Willms, Joanna L.; Shapiro, Kevin A.; Peelen, Marius V.; Pajtas, Petra E.; Costa, Albert; Moo, Lauren R.; Caramazza, Alfonso

2011-01-01

Nouns and verbs are fundamental grammatical building blocks of all languages. Studies of brain-damaged patients and healthy individuals have demonstrated that verb processing can be dissociated from noun processing at a neuroanatomical level. In cases where bilingual patients have a noun or verb deficit, the deficit has been observed in both languages. This suggests that the noun-verb distinction may be based on neural components that are common across languages. Here we investigated the cortical organization of grammatical categories in healthy, early Spanish-English bilinguals using functional magnetic resonance imaging (fMRI) in a morphophonological alternation task. Four regions showed greater activity for verbs than for nouns in both languages: left posterior middle temporal gyrus (LMTG), left middle frontal gyrus (LMFG), pre-supplementary motor area (pre-SMA), and right middle occipital gyrus (RMOG); no regions showed greater activation for nouns. Multi-voxel pattern analysis within verb-specific regions showed indistinguishable activity patterns for English and Spanish, indicating language-invariant bilingual processing. In LMTG and LMFG, patterns were more similar within than across grammatical category, both within and across languages, indicating language-invariant grammatical class information. These results suggest that the neural substrates underlying verb-specific processing are largely independent of language in bilinguals, both at the macroscopic neuroanatomical level and at the level of voxel activity patterns. PMID:21515387

Do physical activity level and body mass index predict recovery from persistent neck pain in men and women of working age? A population-based cohort study.

PubMed

Rasmussen-Barr, E; Bohman, T; Hallqvist, J; Holm, L W; Skillgate, E

2013-09-01

The study sought to examine the gender-specific effects of physical activity level and body mass index on recovery from persistent neck pain (PNP) among citizens of working age in Stockholm, Sweden. A population-based cohort of 1,730 subjects (18-65) with PNP answered surveys in 2002 and 2007. Prognostic factors were self-reported body mass index (BMI) and physical activity level (PAL) at baseline. Analyses were performed with odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI). Women reporting higher physical activity level had higher odds of recovering from PNP than women with sedentary leisure time (OR of 1.5, 95 % CI 1.0-2.4), but no associations were found in men. No associations were found between BMI and recovery from PNP in any analyses. Physical activity seems to be associated with recovery from PNP in women and should therefore be encouraged. Future studies should continue investigating physical activity and lifestyle factors in relation to recovery from persistent neck pain, since these modifiable factors may be considered in interventions.

Level of daily physical activity in chronic obstructive pulmonary disease (COPD) patients according to GOLD classification.

PubMed

Rodó-Pin, Anna; Balañá, Ana; Molina, Lluís; Gea, Joaquim; Rodríguez, Diego A

2017-02-09

The Global Initiative for Chronic Obstructive Lung Disease (GOLD guideline) for patients with chronic obstructive pulmonary disease does not adequately reflect the impact of the disease because does not take into account daily physical activity (DPA). Forty eight patients (12 in each GOLD group) were prospectively recruited. DPA was evaluated by accelerometer. Patients were classified into 3 levels of activity (very inactive, sedentary, active). No significant differences in levels of physical activity among GOLD groups (P=.361) were observed. The percentages of very inactive patients were 33% in group A, 42% in group B, 42% in group C and 59% in group D. In addition, high percentage of sedentary patients were observed through 4 groups, in group A (50%), B and C (42%, each), and group D (41%). COPD patients has very low levels of physical activity at all stages of GOLD classification even those defined as low impact (such as GOLD A). Is necessary to detect patients at risk who might benefit from specific interventions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Role of CYP2E1 immunoglobulin G4 subclass antibodies and complement in pathogenesis of idiosyncratic drug-induced hepatitis.

PubMed

Njoku, Dolores B; Mellerson, Jenelle L; Talor, Monica V; Kerr, Douglas R; Faraday, Nauder R; Outschoorn, Ingrid; Rose, Noel R

2006-02-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.

Do Media Use and Physical Activity Compete in Adolescents? Results of the MoMo Study

PubMed Central

Spengler, Sarah; Mess, Filip; Woll, Alexander

2015-01-01

Purpose The displacement hypothesis predicts that physical activity and media use compete in adolescents; however, findings are inconsistent. A more differentiated approach at determining the co-occurrence of physical activity and media use behaviors within subjects may be warranted. The aim of this study was to determine the co-occurrence of physical activity and media use by identifying clusters of adolescents with specific behavior patterns including physical activity in various settings (school, sports club, leisure time) and different types of media use (watching TV, playing console games, using PC / Internet). Methods Cross-sectional data of 2,083 adolescents (11–17 years) from all over Germany were collected between 2009 and 2012 in the Motorik-Modul Study. Physical activity and media use were self-reported. Cluster analyses (Ward’s method and K-means analysis) were used to identify behavior patterns of boys and girls separately. Results Eight clusters were identified for boys and seven for girls. The clusters demonstrated that a high proportion of boys (33%) as well as girls (42%) show low engagement in both physical activity and media use, irrespective of setting or type of media. Other adolescents are engaged in both behaviors, but either physical activity (35% of boys, 27% of girls) or media use (31% of boys and girls) predominates. These adolescents belong to different clusters, whereat in most clusters either one specific setting of physical activity or a specific combination of different types of media predominates. Conclusion The results of this study support to some extent the hypothesis that media use and physical activity compete: Very high media use occurred with low physical activity behavior, but very high activity levels co-occurred with considerable amounts of time using any media. There was no evidence that type of used media was related to physical activity levels, neither setting of physical activity was related to amount of media use in any pattern. PMID:26629688

Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.

PubMed

Reddish, M A; MacLean, G D; Poppema, S; Berg, A; Longenecker, B M

1996-06-01

Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox adjuvant. The median log2 anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0 - 9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn+ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69+ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69+ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.

Differences in occupational, transportation, domestic, and leisure-time physical activities: do geographical location and socio-cultural status matter?

PubMed

Gauthier, Alain P; Lariviere, Michel; Pong, Raymond; Snelling, Susan; Young, Nancy

2012-02-01

Researchers have recently expressed their concern for the health of Francophones and rural dwellers in Canada. Their levels of physical activity may explain part of the observed differences. However, little is known about the physical activity levels of these 2 groups. The purpose of this study was to assess levels of physical activity among a sample of Francophones and rural dwellers. The study also assessed the associations of various types of physical activity to measures of health status. A quota-based convenience sample of 256 adults from Northern Ontario was surveyed using the IPAQ and the SF-12. There were no significant differences in activity levels between language groups (P = .06) or geographical groups (P = .22) on the combined dependent variables based on MANOVA. Leisure-time physical activity scores were consistently associated to better physical component summary scores of the SF-12. Implications for practice include that leisure-time physical activities have been at the forefront of public health promotion, and our findings support this approach. Further, population specific interventions are indeed important, however, within this Canadian context when identifying target groups one must look beyond sociocultural status or geographical location.

Systems analysis of arrestin pathway functions.

PubMed

Maudsley, Stuart; Siddiqui, Sana; Martin, Bronwen

2013-01-01

To fully appreciate the diversity and specificity of complex cellular signaling events, such as arrestin-mediated signaling from G protein-coupled receptor activation, a complex systems-level investigation currently appears to be the best option. A rational combination of transcriptomics, proteomics, and interactomics, all coherently integrated with applied next-generation bioinformatics, is vital for the future understanding of the development, translation, and expression of GPCR-mediated arrestin signaling events in physiological contexts. Through a more nuanced, systems-level appreciation of arrestin-mediated signaling, the creation of arrestin-specific molecular response "signatures" should be made simple and ultimately amenable to drug discovery processes. Arrestin-based signaling paradigms possess important aspects, such as its specific temporal kinetics and ability to strongly affect transcriptional activity, that make it an ideal test bed for next-generation of drug discovery bioinformatic approaches such as multi-parallel dose-response analysis, data texturization, and latent semantic indexing-based natural language data processing and feature extraction. Copyright © 2013 Elsevier Inc. All rights reserved.

Evidence for a curvilinear relationship between sympathetic nervous system activation and women's physiological sexual arousal.

PubMed

Lorenz, Tierney Ahrold; Harte, Christopher B; Hamilton, Lisa Dawn; Meston, Cindy M

2012-01-01

There is increasing evidence that women's physiological sexual arousal is facilitated by moderate sympathetic nervous system (SNS) activation. Literature also suggests that the level of SNS activation may play a role in the degree to which SNS activity affects sexual arousal. We provide the first empirical examination of a possible curvilinear relationship between SNS activity and women's genital arousal using a direct measure of SNS activation in 52 sexually functional women. The relationship between heart rate variability (HRV), a specific and sensitive marker of SNS activation, and vaginal pulse amplitude (VPA), a measure of genital arousal, was analyzed. Moderate increases in SNS activity were associated with higher genital arousal, while very low or very high SNS activation was associated with lower genital arousal. These findings imply that there is an optimal level of SNS activation for women's physiological sexual arousal. Copyright © 2011 Society for Psychophysiological Research.

Activity Level Assessment Using a Smart Cushion for People with a Sedentary Lifestyle.

PubMed

Ma, Congcong; Li, Wenfeng; Gravina, Raffaele; Cao, Jingjing; Li, Qimeng; Fortino, Giancarlo

2017-10-03

As a sedentary lifestyle leads to numerous health problems, it is important to keep constant motivation for a more active lifestyle. A large majority of the worldwide population, such as office workers, long journey vehicle drivers and wheelchair users, spends several hours every day in sedentary activities. The postures that sedentary lifestyle users assume during daily activities hide valuable information that can reveal their wellness and general health condition. Aiming at mining such underlying information, we developed a cushion-based system to assess their activity levels and recognize the activity from the information hidden in sitting postures. By placing the smart cushion on the chair, we can monitor users' postures and body swings, using the sensors deployed in the cushion. Specifically, we construct a body posture analysis model to recognize sitting behaviors. In addition, we provided a smart cushion that effectively combine pressure and inertial sensors. Finally, we propose a method to assess the activity levels based on the evaluation of the activity assessment index (AAI) in time sliding windows. Activity level assessment can be used to provide statistical results in a defined period and deliver recommendation exercise to the users. For practical implications and actual significance of results, we selected wheelchair users among the participants to our experiments. Features in terms of standard deviation and approximate entropy were compared to recognize the activities and activity levels. The results showed that, using the novel designed smart cushion and the standard deviation features, we are able to achieve an accuracy of (>89%) for activity recognition and (>98%) for activity level recognition.

Activity Level Assessment Using a Smart Cushion for People with a Sedentary Lifestyle

PubMed Central

Li, Wenfeng; Gravina, Raffaele; Cao, Jingjing; Li, Qimeng

2017-01-01

As a sedentary lifestyle leads to numerous health problems, it is important to keep constant motivation for a more active lifestyle. A large majority of the worldwide population, such as office workers, long journey vehicle drivers and wheelchair users, spends several hours every day in sedentary activities. The postures that sedentary lifestyle users assume during daily activities hide valuable information that can reveal their wellness and general health condition. Aiming at mining such underlying information, we developed a cushion-based system to assess their activity levels and recognize the activity from the information hidden in sitting postures. By placing the smart cushion on the chair, we can monitor users’ postures and body swings, using the sensors deployed in the cushion. Specifically, we construct a body posture analysis model to recognize sitting behaviors. In addition, we provided a smart cushion that effectively combine pressure and inertial sensors. Finally, we propose a method to assess the activity levels based on the evaluation of the activity assessment index (AAI) in time sliding windows. Activity level assessment can be used to provide statistical results in a defined period and deliver recommendation exercise to the users. For practical implications and actual significance of results, we selected wheelchair users among the participants to our experiments. Features in terms of standard deviation and approximate entropy were compared to recognize the activities and activity levels. The results showed that, using the novel designed smart cushion and the standard deviation features, we are able to achieve an accuracy of (>89%) for activity recognition and (>98%) for activity level recognition. PMID:28972556

Age-dependent modulation of serum IgE and mast cell sensitization by Nippostrongylus brasiliensis infestation in rats.

PubMed

Turner, K J; Fisher, E H; Mayrhofer, G

1981-08-01

The capacity of N. brasiliensis (Nb) infestation to modify synthesis of ovalbumin (OV) specific IgE antibody was monitored in weanling, juvenile and adult female WAG rats by both passive cutaneous anaphylaxis (PCA) activity and by a rat radio-allergosorbent test (RAST). Infestation with Nb larvae 10 days after immunization with OV produced marginal potentiation of anti-OV Ig antibody production by both RAST and PCA in weanlings, marginal suppression by both parameters in juveniles and was without effect in adults. However, immunization with OV after infestation with Nb partially suppressed anti-OV IgE antibody production in weanlings (RAST) and totally abolished the PCA activity. Although this regime did not impair anti-OV IgE antibody synthesis (RAST) in juveniles, the sera were PCA-negative. In contrast, normal responses were found in adult rats. Negative PCA titres in sera containing high levels of specific antibody occurred when serum total IgE levels were elevated, and are explained on the basis of competition for binding sites on mast cells. The ratio of OV-specific IgE to 'total' IgE is a critical factor in detecting PCA activity.

Design and testing of regulatory cassettes for optimal activity in skeletal and cardiac muscles.

PubMed

Himeda, Charis L; Chen, Xiaolan; Hauschka, Stephen D

2011-01-01

Gene therapy for muscular dystrophies requires efficient gene delivery to the striated musculature and specific, high-level expression of the therapeutic gene in a physiologically diverse array of muscles. This can be achieved by the use of recombinant adeno-associated virus vectors in conjunction with muscle-specific regulatory cassettes. We have constructed several generations of regulatory cassettes based on the enhancer and promoter of the muscle creatine kinase gene, some of which include heterologous enhancers and individual elements from other muscle genes. Since the relative importance of many control elements varies among different anatomical muscles, we are aiming to tailor these cassettes for high-level expression in cardiac muscle, and in fast and slow skeletal muscles. With the achievement of efficient intravascular gene delivery to isolated limbs, selected muscle groups, and heart in large animal models, the design of cassettes optimized for activity in different muscle types is now a practical goal. In this protocol, we outline the key steps involved in the design of regulatory cassettes for optimal activity in skeletal and cardiac muscle, and testing in mature muscle fiber cultures. The basic principles described here can also be applied to engineering tissue-specific regulatory cassettes for other cell types.

Brief Report: CD14brightCD16- monocytes and sCD14 level negatively associate with CD4-memory T-cell frequency and predict HCV-decline on therapy.

PubMed

Judge, Chelsey J; Sandberg, Johan K; Funderburg, Nicholas T; Sherman, Kenneth E; Butt, Adeel A; Kang, Minhee; Landay, Alan L; Lederman, Michael M; Anthony, Donald D

2016-11-01

During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-α-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance.

Evolutionary transitions to new DNA methyltransferases through target site expansion and shrinkage.

PubMed

Rockah-Shmuel, Liat; Tawfik, Dan S

2012-12-01

DNA-binding and modifying proteins show high specificity but also exhibit a certain level of promiscuity. Such latent promiscuous activities comprise the starting points for new protein functions, but this hypothesis presents a paradox: a new activity can only evolve if it already exists. How then, do novel activities evolve? DNA methyltransferases, for example, are highly divergent in their target sites, but how transitions toward novel sites occur remains unknown. We performed laboratory evolution of the DNA methyltransferase M.HaeIII. We found that new target sites emerged primarily through expansion of the original site, GGCC, and the subsequent shrinkage of evolved expanded sites. Variants evolved for sites that are promiscuously methylated by M.HaeIII [GG((A)/(T))CC and GGCGCC] carried mutations in 'gate-keeper' residues. They could thereby methylate novel target sites such as GCGC and GGATCC that were neither selected for nor present in M.HaeIII. These 'generalist' intermediates were further evolved to obtain variants with novel target specificities. Our results demonstrate the ease by which new DNA-binding and modifying specificities evolve and the mechanism by which they occur at both the protein and DNA levels.

Protease-mediated drug delivery

NASA Astrophysics Data System (ADS)

Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

2003-12-01

Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

The Plasma Concentration of the B Cell Activating Factor Is Increased in Children With Acute Malaria

PubMed Central

Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin

2011-01-01

Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells. PMID:21849293

Coagulation parameters in senior athletes practicing endurance sporting activity.

PubMed

Cerneca, E; Simeone, R; Bruno, G; Gombacci, A

2005-12-01

Physical activity is practiced more and more by middle-aged people. We studied the behavior of the coagulation system before and after near-maximum, specific and standardized exercise tests in 2 groups of senior athletes. The subjects of the study were 2 groups of athletes over 40 years of age (ranging 41 to 60 years): 10 rowers and 10 marathon runners. The data were compared with 10 controls (ranging in age from 40 to 71 years) tested on the cycle ergometer. The first group (rowers) was tested on a rowing machine; the second group (marathon runners) performed a maximal exercise on the treadmill. All subjects were tested to a maximal level of cardiovascular and muscular exertion and cardiac and respiratory parameters were monitored. The following coagulation tests were performed before and after maximal exercise: prothrombin time (PT), partial activated thromboplastin time (PTT), fibrinogen (FBG), antithrombin III (ATIII), protein C (PC), protein S (PS), prothrombin fragment 1+2 (F1+2), tissue activator of plasminogen (t-PA) and its inhibitor (PAI). All subjects performed a complete maximal specific test. The results showed all individuals produced a significant increase of FBG, PT and PTT activities and a lowering trend for PC and PS inhibitors after maximal exercise testing. ATIII levels increased significantly in trained subjects. After the test, data regarding fibrinolysis showed higher t-PA levels in athletes as compared with controls. PAI levels indicated a more marked decrease in athletes. The F1+2 showed a moderate but significant increase in the control group. Coagulative tests showed an increase in procoagulant and fibrinolysis parameters in all the groups but the increased fibrinolytic activity in trained athletes indicates a protective factor and greater vascular efficiency. The results demonstrate that sporting activity practiced by middle-aged people accelerates fibrinolytic activity in conditioned subjects. In conclusion, physical activity benefits the coagulation system particularly as regards fibrinolysis.

Be a Choosy Chewer. Nutrition Comes Alive. Level 2. Nutrition Educator's Guide and Work Sheets, Letters to Parents, Recipes. Revised Edition.

ERIC Educational Resources Information Center

Thonney, Patricia; Mapes, Martha C.

This guide provides a nutrition education program for elementary school students that spans kindergarten through Grade 3 as well as providing activities for specific levels. Nutrition education objectives are stated for each grade level: (1) kindergarten--students will become familiar with and motivated to eat a variety of foods; (2) grade…

[Effect of general magnetotherapy on specific activity of blood phagocytes in patients with ischemic heart disease].

PubMed

Ishutin, I S; Klemenkov, S V; Lesovskaia, M I; Spiridonova, M S; Krotova, T K; Ishutin, E I; Tsyganova, O B

2007-01-01

In general magnetotherapy for patients with hyporeactive phagocytes (less than 67% from the level of normal chelicoluminescent response) the adequate level of magnetic induction is 1 mT, for patients with normoreactive phagocytes--0.5 mT and for patients with hyperreactive phagocytes (more than 133% from the level of normal chelicoluminescent response)--0.75 mT daily.

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

PubMed

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

2015-06-26

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

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

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

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

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

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

Antisense RNA Strategies for Metabolic Engineering of Clostridium acetobutylicum

PubMed Central

Desai, Ruchir P.; Papoutsakis, Eleftherios T.

1999-01-01

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by ∼100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes. PMID:10049845

Antisense RNA strategies for metabolic engineering of Clostridium acetobutylicum.

PubMed

Desai, R P; Papoutsakis, E T

1999-03-01

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by approximately 100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes.

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

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

Regulation of Gene Editing Activity Directed by Single-Stranded Oligonucleotides and CRISPR/Cas9 Systems

PubMed Central

Bialk, Pawel; Rivera-Torres, Natalia; Strouse, Bryan; Kmiec, Eric B.

2015-01-01

Single-stranded DNA oligonucleotides (ssODNs) can direct the repair of a single base mutation in human genes. While the regulation of this gene editing reaction has been partially elucidated, the low frequency with which repair occurs has hampered development toward clinical application. In this work a CRISPR/Cas9 complex is employed to induce double strand DNA breakage at specific sites surrounding the nucleotide designated for exchange. The result is a significant elevation in ssODN-directed gene repair, validated by a phenotypic readout. By analysing reaction parameters, we have uncovered restrictions on gene editing activity involving CRISPR/Cas9 complexes. First, ssODNs that hybridize to the non-transcribed strand direct a higher level of gene repair than those that hybridize to the transcribed strand. Second, cleavage must be proximal to the targeted mutant base to enable higher levels of gene editing. Third, DNA cleavage enables a higher level of gene editing activity as compared to single-stranded DNA nicks, created by modified Cas9 (Nickases). Fourth, we calculated the hybridization potential and free energy levels of ssODNs that are complementary to the guide RNA sequences of CRISPRs used in this study. We find a correlation between free energy potential and the capacity of single-stranded oligonucleotides to inhibit specific DNA cleavage activity, thereby indirectly reducing gene editing activity. Our data provide novel information that might be taken into consideration in the design and usage of CRISPR/Cas9 systems with ssODNs for gene editing. PMID:26053390

Regulation of Gene Editing Activity Directed by Single-Stranded Oligonucleotides and CRISPR/Cas9 Systems.

PubMed

Bialk, Pawel; Rivera-Torres, Natalia; Strouse, Bryan; Kmiec, Eric B

2015-01-01

Single-stranded DNA oligonucleotides (ssODNs) can direct the repair of a single base mutation in human genes. While the regulation of this gene editing reaction has been partially elucidated, the low frequency with which repair occurs has hampered development toward clinical application. In this work a CRISPR/Cas9 complex is employed to induce double strand DNA breakage at specific sites surrounding the nucleotide designated for exchange. The result is a significant elevation in ssODN-directed gene repair, validated by a phenotypic readout. By analysing reaction parameters, we have uncovered restrictions on gene editing activity involving CRISPR/Cas9 complexes. First, ssODNs that hybridize to the non-transcribed strand direct a higher level of gene repair than those that hybridize to the transcribed strand. Second, cleavage must be proximal to the targeted mutant base to enable higher levels of gene editing. Third, DNA cleavage enables a higher level of gene editing activity as compared to single-stranded DNA nicks, created by modified Cas9 (Nickases). Fourth, we calculated the hybridization potential and free energy levels of ssODNs that are complementary to the guide RNA sequences of CRISPRs used in this study. We find a correlation between free energy potential and the capacity of single-stranded oligonucleotides to inhibit specific DNA cleavage activity, thereby indirectly reducing gene editing activity. Our data provide novel information that might be taken into consideration in the design and usage of CRISPR/Cas9 systems with ssODNs for gene editing.

Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C 82(OH) 22 and its implication for de novo design of nanomedicine

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

Kang, S. -g.; Zhou, G.; Yang, P.

2012-09-18

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C 82(OH) 22 can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C 82(OH) 22 effectively blocks tumor growth in human pancreatic cancermore » xenografts in a nude mouse model. Enzyme activity assays also show Gd@C 82(OH) 22 not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C 82(OH) 22–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C 82(OH) 22 inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C 82(OH) 22 exhibits specific binding modes near the ligand-specificity loop S1', thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C 82(OH) 22 a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Finally, our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.« less

A receiver operated curve-based evaluation of change in sensitivity and specificity of cotinine urinalysis for detecting active tobacco use.

PubMed

Balhara, Yatan Pal Singh; Jain, Raka

2013-01-01

Tobacco use has been associated with various carcinomas including lung, esophagus, larynx, mouth, throat, kidney, bladder, pancreas, stomach, and cervix. Biomarkers such as concentration of cotinine in the blood, urine, or saliva have been used as objective measures to distinguish nonusers and users of tobacco products. A change in the cut-off value of urinary cotinine to detect active tobacco use is associated with a change in sensitivity and sensitivity of detection. The current study aimed at assessing the impact of using different cut-off thresholds of urinary cotinine on sensitivity and specificity of detection of smoking and smokeless tobacco product use among psychiatric patients. All the male subjects attending the psychiatry out-patient department of the tertiary care multispecialty teaching hospital constituted the sample frame for the current study in a cross-sectionally. Quantitative urinary cotinine assay was done by using ELISA kits of Calbiotech. Inc., USA. We used the receiver operating characteristic (ROC) curve to assess the sensitivity and specificity of various cut-off values of urinary cotinine to identify active smokers and users of smokeless tobacco products. ROC analysis of urinary cotinine levels in detection of self-reported smoking provided the area under curve (AUC) of 0.434. Similarly, the ROC analysis of urinary cotinine levels in detection of self-reported smoking revealed AUC of 0.44. The highest sensitivity and specificity of 100% for smoking were detected at the urinary cut-off value greater than or equal to 2.47 ng/ml. The choice of cut-off value of urinary cotinine used to distinguish nonusers form active users of tobacco products impacts the sensitivity as well as specificity of detection.

Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

PubMed

Schmitt-Ney, M; Happ, B; Hofer, P; Hynes, N E; Groner, B

1992-12-01

The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as well as local signals cooperate in the in vitro regulation of MGF activity.

Urban Latino children's physical activity levels and performance in interactive dance video games: effects of goal difficulty and goal specificity.

PubMed

Gao, Zan; Podlog, Leslie

2012-10-01

To examine the effects of different levels of goal specificity and difficulty on Latino children's performance and physical activity (PA) levels in an after-school program incorporating an interactive dance program (Dance Dance Revolution [DDR]; Konami Corporation). Comparison study. Rose Park Elementary School, Salt Lake City, Utah. Ninety-eight Latino children in the first through sixth grades, aged 7 to 13 years. After the pretest, the participants were randomly assigned into 1 of the following 3 goal-setting conditions: (1) easy, (2) difficult, and (3) best effort (hereinafter referred to as do-your-best goal). Participants' PA levels were measured using piezoelectric pedometers, and steps per minute were used as the outcome variable. Participants' total points for their dance on television screens were retrieved as their performance scores. These outcome variables were assessed again 8 weeks later (posttest score). The multivariate analysis of covariance yielded a significant main effect for the goal-setting condition. Follow-up tests revealed that children who set specific (easy or difficult) goals had significantly greater increased PA levels (mean scores, 10.34 for easy and 22.45 for difficult) and DDR performance (0.011 for easy and 0.67 for difficult) than those in the do-your-best group (0.83 for PA and 0.17 for performance). In addition, children's increased PA levels in the difficult-goal group were significantly higher than those in the easy-goal group. The easy- and difficult-goal groups show a significant improvement on DDR performance. The difficult- goal group also displays the highest improvement on PA levels. Strategies to enhance children's DDR performance and PA levels are discussed in relation to the extant goal-setting literature.

A Report on College-Level Remedial/Developmental Programs in SREB States.

ERIC Educational Resources Information Center

Abraham, Ansley A., Jr.

Remedial and developmental programs at two-year and four-year colleges in states belonging to the Southern Regional Education Board (SREB) were studied, along with placement standards for degree-credit, college-level work in SREB states and institutions. These programs, courses, and activities were designed specifically for first-time entering…

Basic Visual Merchandising. Second Edition. [Student's Manual and] Answer Book/Teacher's Guide.

ERIC Educational Resources Information Center

Luter, Robert R.

This student's manual that features content needed to do tasks related to visual merchandising is intended for students in co-op training stations and entry-level, master employee, and supervisory-level employees. It contains 13 assignments. Each assignment has questions covering specific information and also features activities in which students…

Individualized Instruction and Unipacs.

ERIC Educational Resources Information Center

Kohut, Sylvester, Jr.

Individualized instruction is an educational program in which grade levels and time units are designed to permit the student to work at his own pace and level with the use of unipacs. The unipac, a "unique package," is a specially designed group of learning activities based on specific behavioral objectives chosen by the student. Unipacs consist…

Functional coordination of muscles underlying changes in behavioural dynamics.

PubMed

Vernooij, Carlijn A; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K; Temprado, Jean-Jacques

2016-06-10

The dynamical systems approach addresses Bernstein's degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts' task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts' task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system.

Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance.

PubMed

Šmehilová, Mária; Dobrůšková, Jana; Novák, Ondřej; Takáč, Tomáš; Galuszka, Petr

2016-01-01

Plant hormones cytokinins (CKs) are one of the major mediators of physiological responses throughout plant life span. Therefore, a proper homeostasis is maintained by regulation of their active levels. Besides degradation, CKs are deactivated by uridine diphosphate glycosyltransferases (UGTs). Physiologically, CKs active levels decline in senescing organs, providing a signal to nutrients that a shift to reproductive tissues has begun. In this work, we show CK glucosides distribution in Arabidopsis leaves during major developmental transition phases. Besides continuous accumulation of N-glucosides we detected sharp maximum of the glucosides in senescence. This is caused prevalently by N7-glucosides followed by N9-glucosides and specifically also by trans-zeatin-O-glucoside (tZOG). Interestingly, we observed a similar trend in response to exogenously applied CK. In Arabidopsis, only three UGTs deactivate CKs in vivo: UGT76C1, UGT76C2 and UGT85A1. We thereby show that UGT85A1 is specifically expressed in senescent leaves whereas UGT76C2 is activated rapidly in response to exogenously applied CK. To shed more light on the UGTs physiological roles, we performed a comparative study on UGTs loss-of-function mutants, characterizing a true ugt85a1-1 loss-of-function mutant for the first time. Although no altered phenotype was detected under standard condition we observed reduced chlorophyll degradation with increased anthocyanin accumulation in our experiment on detached leaves accompanied by senescence and stress related genes modulated expression. Among the mutants, ugt76c2 possessed extremely diminished CK N-glucosides levels whereas ugt76c1 showed some specificity toward cis-zeatin (cZ). Besides tZOG, a broader range of CK glucosides was decreased in ugt85a1-1. Performing CK metabolism gene expression profiling, we revealed that activation of CK degradation pathway serves as a general regulatory mechanism of disturbed CK homeostasis followed by decreased CK signaling in all UGT mutants. In contrast, a specific regulation of CKX7, CKX1 and CKX2 was observed for each individual UGT mutant isoform after exogenous CK uptake. Employing an in silico prediction we proposed cytosolic localization of UGT76C1 and UGT76C2, that we further confirmed by GFP tagging of UGT76C2. Integrating all the results, we therefore hypothesize that UGTs possess different physiological roles in Arabidopsis and serve as a fine-tuning mechanism of active CK levels in cytosol.

Try This: Role-Play Party: Talking about Jobs

ERIC Educational Resources Information Center

Benucci, Heather

2015-01-01

This article presents a stand-alone language-learning activity emphasizing speaking. Specifically, students will participate in role plays to describe occupations and job-related duties. The level of the activity is upper beginner or low intermediate and the time required is 45-60 minutes. The goals are: (1) to ask and answer small-talk questions…

Young Scientists Explore the Sun, Moon and Stars. Book 9 Primary Level.

ERIC Educational Resources Information Center

Penn, Linda

Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. The activities specifically focus on space science and allow the children to view themselves as future space scientists. Section one contains…

Binge Drinking in Female College Students: The Association of Physical Activity, Weight Concern, and Depressive Symptoms.

ERIC Educational Resources Information Center

Vickers, Kristin S.; Patten, Christi A.; Bronars, Carrie; Lane, Kristi; Stevens, Susanna R.; Croghan, Ivana T.; Schroeder, Darrell R.; Clark, Matthew M.

2004-01-01

As an initial step in building gender-specific binge drinking intervention programs, the authors investigated the relation of potentially modifiable factors (physical activity level, weight concern, and depressive symptoms) to binge drinking while controlling for the effects of previously established correlates of binge drinking (tobacco and…

Leveling the Playing Field: First Generation Korean American Males and School Based Extracurricular Activities

ERIC Educational Resources Information Center

Levy, Corey

2010-01-01

This study examined the manner in which extracurricular activities impacted the acculturation of first-generation adolescent males. Specifically, the project focused on the influence of organized high school soccer on the development of first-generation adolescent Korean American males. Eight adolescent participants, ranging in age from fourteen…

Nutrition and physical activity randomized control trial in child care centers improves knowledge, policies, and children’s body mass index

PubMed Central

2014-01-01

Background To address the public health crisis of overweight and obese preschool-age children, the Nutrition And Physical Activity Self Assessment for Child Care (NAP SACC) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge, center-level nutrition and physical activity policies and practices, and children’s body mass index (BMI). Methods A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California, Connecticut, and North Carolina, including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old. The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants. Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents. Blinded research assistants reviewed each center’s written health and safety policies, observed nutrition and physical activity practices, and measured randomly selected children’s nutritional intake, physical activity, and height and weight pre- and post-intervention. Results Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge, policies, practices and age- and sex-specific standardized body mass index (zBMI), controlling for state, parent education, and poverty level. Results showed significant increases in providers’ and parents’ knowledge of nutrition and physical activity, center-level improvements in policies, and child-level changes in children’s zBMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points. Conclusions The NAP SACC intervention, as delivered by trained child health professionals such as child care health consultants, increases provider knowledge, improves center policies, and lowers BMI for children in child care centers. More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic. Trial registration National Clinical Trials Number NCT01921842 PMID:24580983

Nutrition and physical activity randomized control trial in child care centers improves knowledge, policies, and children's body mass index.

PubMed

Alkon, Abbey; Crowley, Angela A; Neelon, Sara E Benjamin; Hill, Sherika; Pan, Yi; Nguyen, Viet; Rose, Roberta; Savage, Eric; Forestieri, Nina; Shipman, Linda; Kotch, Jonathan B

2014-03-01

To address the public health crisis of overweight and obese preschool-age children, the Nutrition And Physical Activity Self Assessment for Child Care (NAP SACC) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge, center-level nutrition and physical activity policies and practices, and children's body mass index (BMI). A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California, Connecticut, and North Carolina, including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old. The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants. Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents. Blinded research assistants reviewed each center's written health and safety policies, observed nutrition and physical activity practices, and measured randomly selected children's nutritional intake, physical activity, and height and weight pre- and post-intervention. Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge, policies, practices and age- and sex-specific standardized body mass index (zBMI), controlling for state, parent education, and poverty level. Results showed significant increases in providers' and parents' knowledge of nutrition and physical activity, center-level improvements in policies, and child-level changes in children's zBMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points. The NAP SACC intervention, as delivered by trained child health professionals such as child care health consultants, increases provider knowledge, improves center policies, and lowers BMI for children in child care centers. More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic. National Clinical Trials Number NCT01921842.

Minimally Activated CD8 Autoreactive T Cells Specific for IRBP Express a High Level of Foxp3 and Are Functionally Suppressive

PubMed Central

Peng, Yong; Shao, Hui; Ke, Yan; Zhang, Ping; Han, Gencheng; Kaplan, Henry J.; Sun, Deming

2008-01-01

Purpose Results in previous reports have demonstrated that immunization of the EAU-prone B6 mouse activates both CD4 and CD8 IRBP-specific T cells. The purpose of this study was to investigate structural and functional differences between CD4 and CD8 autoreactive T cells activated by the uveitogenic peptide. Methods Purified CD4 and CD8 isolated from B6 mice immunized with an uveitogenic peptide, interphotoreceptor retin-oid-binding protein (IRBP)1-20, were stimulated in vitro with various doses of immunizing peptide. The activated T cells were determined for cytokine production, expression of Foxp3, and suppressor activity. Results CD4 autoreactive T cells underwent full activation when stimulated with high or medium concentrations of immunizing peptide, whereas a high dose of antigenic peptide resulted in only modest activation of CD8 autoreactive T cells. When stimulated by a low dose (<0.1 μg/mL) of antigen or by of a high dose of antigen and a small amount of TGF-β1, the minimally activated CD8 T cells expressed a high level of Foxp3 and gained suppressor function. Conclusions Minimally activated CD8 autoreactive T cells can be functionally suppressive and may neutralize the tissue-damaging effect of the CD4 autoreactive T cells. PMID:17460277

Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Ye, C.; Chattopadhyay, N.; Sanders, J. L.; Vassilev, P. M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

2000-01-01

Human promyelocytic leukemia cells (HL-60) have been used widely as a model for studying the differentiation of hematopoietic progenitor cells in vitro. After treatment with phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], HL-60 cells differentiate into cells with the phenotype of monocytes/macrophages. We previously showed that peripheral blood monocytes and the murine J774 monocytic cell line express the CaR, and myeloid progenitors in the bone marrow and myeloid cells in peripheral blood other than monocytes express lower levels of the CaR. Therefore, we investigated whether undifferentiated HL-60 cells express a functional G protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) and if the expression of the CaR increases as these cells differentiate along the monocytic lineage. The use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by sequencing of the amplified products, identified an authentic CaR transcript in undifferentiated HL-60 cells. Both immunocytochemistry and Western blot analysis using a CaR-specific antiserum detected low levels of CaR protein expression in undifferentiated HL-60 cells. The levels of CaR protein increased considerably following treatment of the cells with PMA (50 nM) or 1,25(OH)(2)D(3) (100 nM) for 5 days. Northern analysis using a CaR-specific riboprobe identified CaR transcripts in undifferentiated HL-60 cells, but CaR mRNA levels did not change appreciably after treatment with either agent, suggesting that upregulation of CaR protein occurs at a translational level. PMA-treated HL-60 cells expressed a nonselective cation channel (NCC), and the calcimimetic CaR activator, NPS R-467, but not its less active stereoisomer, NPS S-467, as well as the polycationic CaR agonist, neomycin, activated this NCC, demonstrating that the CaR expressed in these cells is functionally active. Therefore, HL-60 cells exhibit an increase in CaR protein expression, occurring at a translational level during their differentiation into cells with a monocyte/macrophage phenotype in response to treatment with PMA or 1, 25(OH)(2)D(3), which is functionally linked to activation of a nonselective cation channel.

A phosphatase threshold sets the level of Cdk1 activity in early mitosis in budding yeast

PubMed Central

Harvey, Stacy L.; Enciso, Germán; Dephoure, Noah; Gygi, Steven P.; Gunawardena, Jeremy; Kellogg, Douglas R.

2011-01-01

Entry into mitosis is initiated by synthesis of cyclins, which bind and activate cyclin-dependent kinase 1 (Cdk1). Cyclin synthesis is gradual, yet activation of Cdk1 occurs in a stepwise manner: a low level of Cdk1 activity is initially generated that triggers early mitotic events, which is followed by full activation of Cdk1. Little is known about how stepwise activation of Cdk1 is achieved. A key regulator of Cdk1 is the Wee1 kinase, which phosphorylates and inhibits Cdk1. Wee1 and Cdk1 show mutual regulation: Cdk1 phosphorylates Wee1, which activates Wee1 to inhibit Cdk1. Further phosphorylation events inactivate Wee1. We discovered that a specific form of protein phosphatase 2A (PP2ACdc55) opposes the initial phosphorylation of Wee1 by Cdk1. In vivo analysis, in vitro reconstitution, and mathematical modeling suggest that PP2ACdc55 sets a threshold that limits activation of Wee1, thereby allowing a low constant level of Cdk1 activity to escape Wee1 inhibition in early mitosis. These results define a new role for PP2ACdc55 and reveal a systems-level mechanism by which dynamically opposed kinase and phosphatase activities can modulate signal strength. PMID:21849476

Predictors of Segmented School Day Physical Activity and Sedentary Time in Children from a Northwest England Low-Income Community

PubMed Central

Taylor, Sarah L.; Curry, Whitney B.; Knowles, Zoe R.; Noonan, Robert J.; McGrane, Bronagh; Fairclough, Stuart J.

2017-01-01

Background: Schools have been identified as important settings for health promotion through physical activity participation, particularly as children are insufficiently active for health. The aim of this study was to investigate the child and school-level influences on children′s physical activity levels and sedentary time during school hours in a sample of children from a low-income community; Methods: One hundred and eighty-six children (110 boys) aged 9–10 years wore accelerometers for 7 days, with 169 meeting the inclusion criteria of 16 h∙day−1 for a minimum of three week days. Multilevel prediction models were constructed to identify significant predictors of sedentary time, light, and moderate to vigorous physical activity during school hour segments. Child-level predictors (sex, weight status, maturity offset, cardiorespiratory fitness, physical activity self-efficacy, physical activity enjoyment) and school-level predictors (number on roll, playground area, provision score) were entered into the models; Results: Maturity offset, fitness, weight status, waist circumference-to-height ratio, sedentary time, moderate to vigorous physical activity, number of children on roll and playground area significantly predicted physical activity and sedentary time; Conclusions: Research should move towards considering context-specific physical activity and its correlates to better inform intervention strategies. PMID:28509887

Barriers to physical activity in people with type 2 diabetes enrolled in a worksite diabetes disease management program.

PubMed

Erickson, Deborah

2013-01-01

The purpose of this study was to explore the level of physical activity, barriers to physical activity, and strategies used to meet physical activity goals in people with type 2 diabetes (T2DM). A descriptive, cross-sectional design was used in a sample of 75 adults with T2DM enrolled in a worksite diabetes disease management program (WDDMP). Participants self-reported the length of time they engaged in moderate-intensity physical activity, the frequency of general and specific physical activity, and barriers to participating in physical activity. Participants who chose to work on physical activity as part of their diabetes self-management had a higher stage of change for physical activity and participated in more general and specific physical activity than did those participants who did not choose to work on physical activity. Participants who were active reported fewer barriers to physical activity and chose to work on more self-care areas to control their diabetes than did those participants who were inactive. Participants who chose to work on physical activity participated in more general and specific physical activity and had a higher stage of change for physical activity. Stage of change affects physical activity. While results provide support for the stages of change construct of the transtheoretical model of change, the results do not support that the WDDMP assisted participants in achieving their physical activity goals.

A Systematic Review of Montessori-Based Activities for Persons With Dementia.

PubMed

Sheppard, Christine L; McArthur, Caitlin; Hitzig, Sander L

2016-02-01

Montessori-based activities are becoming a popular approach for the care of older adults living with dementia. The aim of this study was to systematically assess the quality of the research examining the benefits of Montessori-based activities for persons with dementia. Six peer-reviewed databases were systematically searched for all relevant articles published until April 2015. Included articles were peer-reviewed studies published in English that employed Montessori-based activities with persons with dementia. Methodological quality was assessed by 2 independent raters using the Physiotherapy Evidence Database Scale or the Downs and Black evaluation tool. Levels of evidence were assigned to the study design using a modified Sackett scale. One hundred fifty articles were identified, and 14 were selected for inclusion. Level-2 evidence examining the impact of Montessori-based activities on eating behaviors suggested that difficulties with eating could be reduced with Montessori training. There was limited level-4 evidence for the benefits of Montessori-based activities on cognition, wherein benefits appeared to be specific to lower-level cognitive abilities including memory and attention. Finally, there is level-1 (n = 1), level-2 (n = 3), and level-4 (n = 6) evidence for the benefits of Montessori-based activities on engagement and affect, whereby constructive engagement and positive affect were heightened. Overall, there is a strong level of evidence for the benefits of Montessori-based activities on eating behaviors and weak evidence for the benefits on cognition. Evidence for the benefits of Montessori-based activities on engagement and affect are mixed. Future research is needed to examine the long-term benefits of Montessori-based activities. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Activation of c-Raf-1 kinase signal transduction pathway in alpha(7) integrin-deficient mice.

PubMed

Saher, G; Hildt, E

1999-09-24

Integrin alpha(7)-deficient mice develop a novel form of muscular dystrophy. Here we report that deficiency of alpha(7) integrin causes an activation of the c-Raf-1/mitogen-activated protein (MAP) 2 kinase signal transduction pathway in muscle cells. The observed activation of c-Raf-1/MAP2 kinases is a specific effect, because the alpha(7) integrin deficiency does not cause unspecific stress as determined by measurement of the Hsp72/73 level and activity of the JNK2 kinase. Because an increased level of activated FAK was found in muscle of alpha(7) integrin-deficient mice, the activation of c-Raf-1 kinase is triggered most likely by an integrin-dependent pathway. In accordance with this, in the integrin alpha(7)-deficient mice, part of the integrin beta(1D) variant in muscle is replaced by the beta(1A) variant, which permits the FAK activation. A recent report describes that integrin activity can be down-modulated by the c-Raf-1/MAP2 kinase pathway. Specific activation of the c-Raf-1/MAP2 kinases by cell-permeable peptides in skeletal muscle of rabbits causes degeneration of muscle fibers. Therefore, we conclude that in alpha(7) integrin-deficient mice, the continuous activation of c-Raf-1 kinase causes a permanent reduction of integrin activity diminishing integrin-dependent cell-matrix interactions and thereby contributing to the development of the dystrophic phenotype.

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

PubMed Central

Villa, James P.; Bertenshaw, Greg P.; Bond, Judith S.

2008-01-01

SUMMARY The protease domains of the evolutionarily-related α and ß subunits of meprin metalloproteases are approximately 55% identical at the amino acid level, however, their substrate and peptide bond specificities differ markedly. The meprin ß subunit favors acidic residues proximal to the scissile bond, while the α subunit prefers small or aromatic amino acids flanking the scissile bond. Thus gastrin, a peptide that contains a string of five Glu residues, is an excellent substrate for meprin ß while it is not hydrolyzed by meprin α. Work herein aimed to identify critical amino acids in the meprin active sites that determine the substrate specificity differences. Sequence alignments and homology models, based on the crystal structure of the crayfish astacin, showed electrostatic differences within the meprin active sites. Site-directed mutagenesis of active site residues demonstrated that replacement of a hydrophobic residue by a basic amino acid enabled the meprin α protease to cleave gastrin. The meprin αY199K mutant was most effective; the corresponding mutation of meprin ßK185Y resulted in decreased activity toward gastrin. Peptide cleavage site determinations and kinetic analyses using a variety of peptides extended evidence that meprin αTyr199/ßLys185 are substrate specificity determinants in meprin active sites. These studies shed light on the molecular basis for the substrate specificity differences of astacin metalloproteinases. PMID:12888571

British isles lupus assessment group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus

PubMed Central

Yee, Chee-Seng; Farewell, Vernon; Isenberg, David A; Rahman, Anisur; Teh, Lee-Suan; Griffiths, Bridget; Bruce, Ian N; Ahmad, Yasmeen; Prabu, Athiveeraramapandian; Akil, Mohammed; McHugh, Neil; D'Cruz, David; Khamashta, Munther A; Maddison, Peter; Gordon, Caroline

2007-01-01

Objective To determine the construct and criterion validity of the British Isles Lupus Assessment Group 2004 (BILAG-2004) index for assessing disease activity in systemic lupus erythematosus (SLE). Methods Patients with SLE were recruited into a multicenter cross-sectional study. Data on SLE disease activity (scores on the BILAG-2004 index, Classic BILAG index, and Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), investigations, and therapy were collected. Overall BILAG-2004 and overall Classic BILAG scores were determined by the highest score achieved in any of the individual systems in the respective index. Erythrocyte sedimentation rates (ESRs), C3 levels, C4 levels, anti–double-stranded DNA (anti-dsDNA) levels, and SLEDAI-2K scores were used in the analysis of construct validity, and increase in therapy was used as the criterion for active disease in the analysis of criterion validity. Statistical analyses were performed using ordinal logistic regression for construct validity and logistic regression for criterion validity. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results Of the 369 patients with SLE, 92.7% were women, 59.9% were white, 18.4% were Afro-Caribbean and 18.4% were South Asian. Their mean ± SD age was 41.6 ± 13.2 years and mean disease duration was 8.8 ± 7.7 years. More than 1 assessment was obtained on 88.6% of the patients, and a total of 1,510 assessments were obtained. Increasing overall scores on the BILAG-2004 index were associated with increasing ESRs, decreasing C3 levels, decreasing C4 levels, elevated anti-dsDNA levels, and increasing SLEDAI-2K scores (all P < 0.01). Increase in therapy was observed more frequently in patients with overall BILAG-2004 scores reflecting higher disease activity. Scores indicating active disease (overall BILAG-2004 scores of A and B) were significantly associated with increase in therapy (odds ratio [OR] 19.3, P < 0.01). The BILAG-2004 and Classic BILAG indices had comparable sensitivity, specificity, PPV, and NPV. Conclusion These findings show that the BILAG-2004 index has construct and criterion validity. PMID:18050213

Toward an objective indexing system for ADHD-screening using children's activity monitoring.

PubMed

Kam, Hye Jin; Choi, Jong Pil; Park, Rae Woong

2008-11-06

Signs of ADHD are discernible in specific situations, and usually assessed according to subjective impressions. We performed a preliminary comparative study from children's activity at a natural classroom environment with 3-axis accelerator for a feasible objective index. From a total of 157 children (7-9 yrs) and clinically diagnosed 24 children out of them, variances in 1-min epoch mean activity had shown significant differences among the subgroups: (1) ADHD=.0194, Other Diseases=.0080, Normal=.0009; (2) ADHD=.0194, non-ADHD=.0057(p<.01, respectively). There were also significant differences in high-level activity (>1.6G) features among subgroups with the same order (p<.01, respectively). ADHD patients exhibited more dispersed activities and higher high-level activity ratio than normal. Activity features can be useful to build an objective indexing system for screening ADHD patients.

Predominate HIV1-specific IgG activity in various mucosal compartments of HIV1-infected individuals.

PubMed

Lü, F X

2000-10-01

Evaluating mucosal humoral immunity is important for understanding local immunity induced by HIV infection or vaccination and designing prophylactic strategies. To characterize the mucosal humoral immunity following HIV infection, the levels of immunoglobulins (Igs), antibodies (Abs), and HIV1-specific Ab activity were evaluated in cervicovaginal secretions (CVS), saliva, breast milk, and sera of HIV-infected individuals. HIV1-specific IgG activity was significantly higher than that of IgA in CVS, saliva, and breast milk. The highest HIV1-specific IgG activity was found in breast milk. The data suggest that anti-HIV1 Abs in CVS were most likely serum derived. However, HIV1-specific Abs in saliva and breast milk were mainly locally produced. The prevalence of HIV1-specific Abs in seropositive subjects was 97% for IgG and 95% for IgA in CVS, 100% for IgG and 80% for IgA in saliva, and 59% for IgG and 94% for IgA in breast milk. These data provide evidence for both a better understanding of the nature of humoral mucosal responses after HIV1 infection and the development of strategies to induce desirable functional mucosal immunity for preventing HIV transmission. Copyright 2000 Academic Press.

The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements

PubMed Central

Uhlirova, Hana; Kılıç, Kıvılcım; Tian, Peifang; Sakadžić, Sava; Thunemann, Martin; Desjardins, Michèle; Saisan, Payam A.; Nizar, Krystal; Yaseen, Mohammad A.; Hagler, Donald J.; Vandenberghe, Matthieu; Djurovic, Srdjan; Andreassen, Ole A.; Silva, Gabriel A.; Masliah, Eliezer; Vinogradov, Sergei; Buxton, Richard B.; Einevoll, Gaute T.; Boas, David A.; Dale, Anders M.; Devor, Anna

2016-01-01

The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed ‘bottom-up’ forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in the way they drive changes in cerebral blood flow, cerebral metabolic rate of O2 (measurable with quantitative functional Magnetic Resonance Imaging), and electrical currents/potentials (measurable with magneto/electroencephalography). This forward model would then provide the ‘ground truth’ for the development of new tools for tackling the inverse problem—estimation of neuronal activity from multimodal non-invasive imaging data. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574309

Facilitators and barriers to physical activity as perceived by older adults with intellectual disability.

PubMed

van Schijndel-Speet, Marieke; Evenhuis, Heleen M; van Wijck, Ruud; van Empelen, Pepijn; Echteld, Michael A

2014-06-01

Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID for specific physical activities, and to gain insight into facilitators and barriers to engaging into PA. Fourteen in-depth interviews and four focus groups were undertaken, with a total of 40 older adults with mild and moderate ID included in the analysis. NVivo software was used for analysing the transcribed verbatim interviews. In total, 30 codes for facilitators and barriers were identified. Themes concerning facilitators to PA were enjoyment, support from others, social contact and friendship, reward, familiarity, and routine of activities. Themes concerning barriers to PA were health and physiological factors, lack of self-confidence, lack of skills, lack of support, transportation problems, costs, and lack of appropriate PA options and materials. The results of the present study suggest that older adults with ID may benefit from specific PA programs, adapted to their individual needs and limitations. Results can be used for developing feasible health promotion programs for older adults with ID.

Regulation of the activity of the promoter of RNA-induced silencing, C3PO.

PubMed

Sahu, Shriya; Williams, Leo; Perez, Alberto; Philip, Finly; Caso, Giuseppe; Zurawsky, Walter; Scarlata, Suzanne

2017-09-01

RNA-induced silencing is a process which allows cells to regulate the synthesis of specific proteins. RNA silencing is promoted by the protein C3PO (component 3 of RISC). We have previously found that phospholipase Cβ, which increases intracellular calcium levels in response to specific G protein signals, inhibits C3PO activity towards certain genes. Understanding the parameters that control C3PO activity and which genes are impacted by G protein activation would help predict which genes are more vulnerable to downregulation. Here, using a library of 10 18 oligonucleotides, we show that C3PO binds oligonucleotides with structural specificity but little sequence specificity. Alternately, C3PO hydrolyzes oligonucleotides with a rate that is sensitive to substrate stability. Importantly, we find that oligonucleotides with higher Tm values are inhibited by bound PLCβ. This finding is supported by microarray analysis in cells over-expressing PLCβ1. Taken together, this study allows predictions of the genes whose post-transcriptional regulation is responsive to the G protein/phospholipase Cβ/calcium signaling pathway. © 2017 The Protein Society.

Regulated expression of a novel TCP domain transcription factor indicates an involvement in the control of meristem activation processes in Solanum tuberosum.

PubMed

Faivre-Rampant, Odile; Bryan, Glenn J; Roberts, Alison G; Milbourne, Daniel; Viola, Roberto; Taylor, Mark A

2004-04-01

In this study, the aim was to determine whether TCP transcription factors are implicated in meristem activation in potato (Solanum tuberosum). By searching a database of potato EST sequences, with a sequence characteristically conserved in TCP domains, a potato tcp gene was identified. A BAC clone containing the tcp sequence was isolated and the genomic sequence was determined. Using a CAPS marker assay, the potato tcp gene (sttcp1) was mapped to chromosome 8. In dormant buds, relatively high levels of sttcp1-specific transcript were detected by in situ hybridization. By contrast, in sprouting buds, no expression of the sttcp1 could be detected. Furthermore, an inverse relationship between axillary bud size and the steady-state level of the sstcp1 transcript was demonstrated. In non-growing buds exhibiting correlative inhibition, sttcpI-specific transcript levels were also relatively high, but rapidly decreased when apical dominance was removed by excision of the apical bud.

The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

PubMed

Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

2016-01-01

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Simultaneous saccharification and fermentation of Agave tequilana fructans by Kluyveromyces marxianus yeasts for bioethanol and tequila production.

PubMed

Flores, Jose-Axel; Gschaedler, Anne; Amaya-Delgado, Lorena; Herrera-López, Enrique J; Arellano, Melchor; Arrizon, Javier

2013-10-01

Agave tequilana fructans (ATF) constitute a substrate for bioethanol and tequila industries. As Kluyveromyces marxianus produces specific fructanases for ATF hydrolysis, as well as ethanol, it can perform simultaneous saccharification and fermentation. In this work, fifteen K. marxianus yeasts were evaluated to develop inoculums with fructanase activity on ATF. These inoculums were added to an ATF medium for simultaneous saccharification and fermentation. All the yeasts, showed exo-fructanhydrolase activity with different substrate specificities. The yeast with highest fructanase activity in the inoculums showed the lowest ethanol production level (20 g/l). Five K. marxianus strains were the most suitable for the simultaneous saccharification and fermentation of ATF. The volatile compounds composition was evaluated at the end of fermentation, and a high diversity was observed between yeasts, nevertheless all of them produced high levels of isobutyl alcohol. The simultaneous saccharification and fermentation of ATF with K. marxianus strains has potential for industrial application. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gender differences in the roles and functions of inpatient psychiatric nurses.

PubMed

Torkelson, Diane J; Seed, Mary S

2011-03-01

This study explored the difference between male and female psychiatric nurses' job performance and job satisfaction levels on an acute care inpatient unit. The amount of time male (n = 28) and female (n = 45) nurses spent on 10 specific functions and roles during a shift were observed and recorded. The nurses also self-rated the amount of time they spent on these specific functions and roles. The observed and self-rated functions were then correlated with job satisfaction. Female nurses were observed and self-rated as spending significantly more time on patient care activities, and these activities were significantly correlated with higher job satisfaction levels. Male nurses who self-rated spending more time on patient care activities had significantly lower job satisfaction scores. Findings confirm the concepts from social role theory that gender identity and expectations influence job performance in psychiatric nursing. The results offer insight for increasing job satisfaction and recruitment/retention efforts. Copyright 2011, SLACK Incorporated.

Psychosocial Risks Generated By Assets Specific Design Software

NASA Astrophysics Data System (ADS)

Remus, Furtună; Angela, Domnariu; Petru, Lazăr

2015-07-01

The human activity concerning an occupation is resultant from the interaction between the psycho-biological, socio-cultural and organizational-occupational factors. Tehnological development, automation and computerization that are to be found in all the branches of activity, the level of speed in which things develop, as well as reaching their complexity, require less and less physical aptitudes and more cognitive qualifications. The person included in the work process is bound in most of the cases to come in line with the organizational-occupational situations that are specific to the demands of the job. The role of the programmer is essencial in the process of execution of ordered softwares, thus the truly brilliant ideas can only come from well-rested minds, concentrated on their tasks. The actual requirements of the jobs, besides the high number of benefits and opportunities, also create a series of psycho-social risks, which can increase the level of stress during work activity, especially for those who work under pressure.

[Intracellular Protein Degradation in Growth of Atlantic Salmon, Salmo salar L].

PubMed

Lysenko, L A; Kantserova, N P; Krupnova, M Yu; Veselov, A E; Nemova, N N

2015-01-01

A brief review on the common characteristics and specific features of proteolytic machinery in fish skeletal muscles (based on Atlantic salmon, Salmo salar L., Salmonidae) has been given. Among a variety of proteases in the muscle tissue, those determining protein degradation level in developing and intensively growing muscles in salmon young and by this way regulating protein retention intensity and growth at all namely lysosomal cathepsins B and D and calcium-dependent proteases (calpains) were comprehensively studied. Revealed age-related differences in intracellular protease activity in salmon skeletal muscles indicate the role of proteolysis regulation in growth in general and a specific role of the individual proteolytic enzymes in particular. The data on negative correlation of cathepsin D and calpain activity levels in muscles and the rate of weight increase in juvenile salmon were obtained. A revealed positive correlation of cathepsin B activity and morphometric parameters in fish young presumably indicates its primary contribution to non-myofibrillar protein turnover.

The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

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

Liu, Senyan; Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201; Yao, Yunyi

The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity withmore » the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity.« less

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem.

PubMed

Kišidayová, Svetlana; Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities.

The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem

PubMed Central

Pristaš, Peter; Zimovčáková, Michaela; Blanár Wencelová, Monika; Homol'ová, Lucia; Mihaliková, Katarína; Čobanová, Klaudia; Grešáková, Ľubomíra; Váradyová, Zora

2018-01-01

Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities. PMID:29324899

Correlation of Level of Trauma Activation With Emergency Department Intervention.

PubMed

Cooper, Michael C; Srivastava, Geetanjali

2018-06-01

In-hospital trauma team activation criteria are formulated to identify severely injured patients requiring specialized multidisciplinary care. Efficacy of trauma activation (TA) criteria is commonly measured by emergency department (ED) disposition, injury severity score, and mortality. Necessity of critical ED interventions is another measure that has been proposed to evaluate the appropriateness of TA criteria. Two-year retrospective cohort study of 1715 patients from our trauma registry at a Level 1 pediatric trauma center. We abstracted data on acute interventions, level and criterion of TA, ED disposition, and mortality. We report odds ratio (OR) with 95% confidence intervals (CIs), positive predictive value, and frequency of acute interventions. Trauma activation was initiated for 947 (55%) of the 1715 patients. There were 426 ED interventions performed on 235 patients (14%); 67.8% were in level 1 activations; 17.6% in level 2, and 14.6% in level 3. Highest-level activations were highly associated with need for ED interventions (OR, 16.1; 95% CI, 11.5-22.4). The ORs for requiring an ED intervention were low for lower level activations (OR, 0.4; 95% CI, 0.3-0.5), trauma service consults (OR, 0.3; 95% CI, 0.2-0.4), and certain mechanism-based criteria. The ORs for ED intervention for isolated motor vehicle collision (0.2; 95% CI, 0.1-0.7), isolated all-terrain vehicle rollover (0.4; 95% CI, 0.1-1.7), and suspected spinal cord injury (0.5; 95% CI, 0.1-3.7) were significantly lower than 1. Highest-level activation criteria correlate with high utilization of ED resources and interventions. Lower level activation criteria and trauma service consult criteria are not highly correlated with need for ED interventions. Downgrading isolated motor vehicle collision and all-terrain vehicle rollovers and suspected spinal cord injury to lower level activations could decrease the overtriage rate, and adding age-specific bradycardia as a physiologic criterion could improve our undertriage rate.

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

PubMed

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

2007-05-01

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

Feasibility and Effectiveness of Using Wearable Activity Trackers in Youth: A Systematic Review

PubMed Central

McNarry, Melitta A; Mackintosh, Kelly A

2016-01-01

Background The proliferation and popularity of wearable activity trackers (eg, Fitbit, Jawbone, Misfit) may present an opportunity to integrate such technology into physical activity interventions. While several systematic reviews have reported intervention effects of using wearable activity trackers on adults’ physical activity levels, none to date have focused specifically on children and adolescents. Objective The aim of this review was to examine the effectiveness of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. We also examined the feasibility of using such technology in younger populations (age range 5-19 years). Methods We conducted a systematic search of 5 electronic databases, reference lists, and personal archives to identify articles published up until August 2016 that met the inclusion criteria. Articles were included if they (1) specifically examined the use of a wearable device within an intervention or a feasibility study; (2) included participants aged 5-19 years old; (3) had a measure of physical activity as an outcome variable for intervention studies; (4) reported process data concerning the feasibility of the device in feasibility studies; and (5) were published in English. Data were analyzed in August 2016. Results In total, we identified and analyzed 5 studies (3 intervention, 2 feasibility). Intervention delivery ranged from 19 days to 3 months, with only 1 study using a randomized controlled trial design. Wearable activity trackers were typically combined with other intervention approaches such as goal setting and researcher feedback. While intervention effects were generally positive, the reported differences were largely nonsignificant. The feasibility studies indicated that monitor comfort and design and feedback features were important factors to children and adolescents. Conclusions There is a paucity of research concerning the effectiveness and feasibility of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. While there are some preliminary data to suggest these devices may have the potential to increase activity levels through self-monitoring and goal setting in the short term, more research is needed to establish longer-term effects on behavior. PMID:27881359

The neural correlates of specific versus general autobiographical memory construction and elaboration

PubMed Central

Holland, Alisha C.; Addis, Donna Rose; Kensinger, Elizabeth A.

2011-01-01

We examined the neural correlates of specific (i.e., unique to time and place) and general (i.e., extended in or repeated over time) autobiographical memories (AMs) during their initial construction and later elaboration phases. The construction and elaboration of specific and general events engaged a widely distributed set of regions previously associated with AM recall. Specific (vs. general) event construction preferentially engaged prefrontal and medial temporal lobe regions known to be critical for memory search and retrieval processes. General event elaboration was differentiated from specific event elaboration by extensive right-lateralized prefrontal cortex (PFC) activity. Interaction analyses confirmed that PFC activity was disproportionately engaged by specific AMs during construction, and general AMs during elaboration; a similar pattern was evident in regions of the left lateral temporal lobe. These neural differences between specific and general AM construction and elaboration were largely unrelated to reported differences in the level of detail recalled about each type of event. PMID:21803063

Strategies for prevention and management of musculoskeletal conditions. Low back pain (non-specific).

PubMed

Krismer, M; van Tulder, M

2007-02-01

Low back pain (LBP) is defined as pain localised between the 12th rib and the inferior gluteal folds, with or without leg pain. Most cases are non-specific, but in about 10% of cases a specific cause is identified. Red flags are typical signs or symptoms that are frequently associated with specific LBP. Yellow flags are prognostic factors associated with a more unfavourable and often chronic disabling course of the disease. LBP has a lifetime prevalence of 60-85%. At any one time, about 15% of adults have LBP. LBP poses an economic burden to society, mainly in terms of the large number of work days lost (indirect costs) and less so by direct treatment costs. A substantial proportion of individuals with chronic LBP has been found to have chronic widespread pain. LBP is often associated with other pain manifestations such as headache, abdominal pain and pain in different locations of the extremities. Widespread pain is associated with a worse prognosis compared to localised LBP. Treatment targets are reduction of pain and better activity/participation, including prevention of disability as well as maintainance of work capacity. The evidence from selected and appraised guidelines, systematic reviews and major clinical studies was classified into four levels, level Ia being the best level with evidence from meta-analysis of randomised controlled trials. Key recommendations (level Ia): fitness programmes and advice to stay active can reduce pain, improve function and can prevent LBP becoming chronic. Simple analgesics, NSAIDs and muscle relaxants can reduce pain and can improve and maintain function. Maintaining physical activity, avoiding rest and manual therapy can reduce pain and maintain and restore function in acute LBP. Behavioural treatment can prevent LBP becoming chronic. Aerobic fitness and endurance training, behavioural treatment and multi-disciplinary treatment programmes can reduce pain and can improve/maintain function in chronic LBP.

Probing the Molecular Mechanism of Hypericin-Induced Parasite Death Provides Insight into the Role of Spermidine beyond Redox Metabolism in Leishmania donovani

PubMed Central

Singh, Shalini; Sarma, Shyamali; Katiyar, Shashank P.; Das, Mousumi; Bhardwaj, Ruchika; Sundar, Durai

2014-01-01

Hypericin, a natural compound from Hypericum perforatum (St. John's wort), has been identified as a specific inhibitor of Leishmania donovani spermidine synthase (LdSS) using integrated computational and biochemical approaches. Hypericin showed in vitro inhibition of recombinant LdSS enzyme activity. The in vivo estimation of spermidine levels in Leishmania promastigotes after hypericin treatment showed significant decreases in the spermidine pools of the parasites, indicating target specificity of the inhibitor molecule. The inhibitor, hypericin, showed significant antileishmanial activity, and the mode of death showed necrosis-like features. Further, decreased trypanothione levels and increased glutathione levels with elevated reactive oxygen species (ROS) levels were observed after hypericin treatment. Supplementation with trypanothione in the medium with hypericin treatment restored in vivo trypanothione levels and ROS levels but could not prevent necrosis-like death of the parasites. However, supplementation with spermidine in the medium with hypericin treatment restored in vivo spermidine levels and parasite death was prevented to a large extent. The data overall suggest that the parasite death due to spermidine starvation as a result of LdSS inhibition is not related to elevated levels of reactive oxygen species. This suggests the involvement of spermidine in processes other than redox metabolism in Leishmania parasites. Moreover, the work provides a novel scaffold, i.e., hypericin, as a potent antileishmanial molecule. PMID:25313212

Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects.

PubMed

Dwivedi, Yogesh; Rao, Jagadeesh Sridhara; Rizavi, Hooriyah S; Kotowski, Jacek; Conley, Robert R; Roberts, Rosalinda C; Tamminga, Carol A; Pandey, Ghanshyam N

2003-03-01

Cyclic adenosine monophosphate response element binding protein (CREB) is a transcription factor that, on phosphorylation by protein kinases, is activated, and in response, regulates the transcription of many neuronally expressed genes. In view of the recent observations that catalytic properties and/or expression of many kinases that mediate their physiological responses through the activation of CREB are altered in the postmortem brain of subjects who commit suicide (hereafter referred to as suicide subjects), we examined the status of CREB in suicidal behavior. These studies were performed in Brodmann area (BA) 9 and hippocampus obtained from 26 suicide subjects and 20 nonpsychiatric healthy control subjects. Messenger RNA levels of CREB and neuron-specific enolase were determined in total RNA by means of quantitative reverse transcriptase-polymerase chain reaction. Protein levels and the functional characteristics of CREB were determined in nuclear fractions by means of Western blot and cyclic adenosine monophosphate response element (CRE)-DNA binding activity, respectively. In the same nuclear fraction, we determined the catalytic activity of cyclic adenosine monophosphate-stimulated protein kinase A by means of enzymatic assay. We observed a significant reduction in messenger RNA and protein levels of CREB, CRE-DNA binding activity, and basal and cyclic adenosine monophosphate-stimulated protein kinase A activity in BA 9 and hippocampus of suicide subjects, without any change in messenger RNA levels of neuron-specific enolase in BA 9. Except for protein kinase A activity, changes in CREB expression and CRE-DNA binding activity were present in all suicide subjects, irrespective of diagnosis. These changes were unrelated to postmortem intervals, age, sex, or antidepressant treatment. Given the significance of CREB in mediating various physiological functions through gene transcription, our results of decreased expression and functional characteristics of CREB in postmortem brain of suicide subjects suggest that CREB may play an important role in suicidal behavior.

“The Early Specialised Bird Catches the Worm!” – A Specialised Sampling Model in the Development of Football Talents

PubMed Central

Sieghartsleitner, Roland; Zuber, Claudia; Zibung, Marc; Conzelmann, Achim

2018-01-01

Characteristics of learning activities in early sport participation play a key role in the development of the sporting talent. Therefore, pathways of specialisation or diversification/sampling are as well debated as the implementation of practice- or play-oriented activities. The related issues are currently perceived as a two-dimensional construct of domain specificity and performance orientation. In this context, it has been shown that early specialisation, with experiences in practice and play, has led to Swiss junior national team football players reaching higher success levels as adults. This study aimed to examine whether a similar approach improves chances of even being selected for junior national teams from a broader sample. Hence, 294 youth players answered retrospective questionnaires on their early sport participation when entering the Swiss football talent development programme. Using the person-oriented Linking of Clusters after removal of a Residue (LICUR) method, volumes of in-club practice, free play and activities besides football until 12 years of age were analysed along with age at initial club participation. According to the results, clusters of Football enthusiasts (p = 0.01) with the most free play and above average in-club practice and Club players (p = 0.02) with the most in-club practice and average free play had a greater chance of reaching junior national team level. Thus, high levels of domain-specific activities seem to increase the chances of junior national team participation. Furthermore, the most successful constellation (Football enthusiasts) may illustrate the relevance of domain-specific diversity, induced by several types of practice and play. In line with previous studies, specialising in football and sampling different experiences within this specific domain seems to be the most promising pathway. Therefore, we argue that the optimal model for the development of football talents is a specialised sampling model. PMID:29515500

Prospective evaluation of free-breathing diffusion-weighted imaging for the detection of inflammatory bowel disease with MR enterography in childhood population

PubMed Central

Dubron, Céline; Avni, Freddy; Boutry, Nathalie; Turck, Dominique; Duhamel, Alain

2016-01-01

Objective: To evaluate prospectively the performance of diffusion-weighted imaging (DWI) for the detection of active lesions on MR enterography (MRE) in children with inflammatory bowel disease (IBD). Methods: MRE of 48 children (mean age 13 years) with suspected or known IBD were blindly analysed by 2 independent readers for the presence of active lesions. Two sets of imaging including DWI and gadolinium-enhanced imaging (GEI) were reviewed. A reader consensus was obtained. The gold standard was histopathological findings. In patient-level analysis and segment-level analysis, sensitivity and specificity were calculated for DWI and GEI and compared using McNemar's test or logistic random-effects models. Results: At least 1 active lesion was confirmed in 42 (87.5%) children. Sensitivity and specificity for the detection of at least one lesion were 88.1% (95% CI, 74.3–96.1) and 83.3% (95% CI, 35.9–99.6), respectively, for DWI and 66.7% (95% CI, 50.4–80.4) and 83.3% (95% CI, 35.9–99.6), respectively, for GEI. In segment-level analysis, sensitivity and specificity for the detection of specific segment lesions were 62.5% (95% CI, 48.1–75) and 97.1% (95% CI, 93.5–98.7), respectively, for DWI and 45.7% (95% CI, 30.8–61.3) and 98.2% (95% CI, 95.3–99.4), respectively, for GEI. The sensitivity of DWI was significantly better than that of GEI per patient (p = 0.004) and per segment (p = 0.028). Conclusion: DWI demonstrates better performance than GEI for the detection of active lesions in children with IBD. Advances in knowledge: Examination with no intravenous injection–DWI can replace T1 weighted images when paediatric patients are screened with MRE for IBD. Examination performed in free breathing is better tolerated by children. PMID:26838954

Prospective evaluation of free-breathing diffusion-weighted imaging for the detection of inflammatory bowel disease with MR enterography in childhood population.

PubMed

Dubron, Céline; Avni, Freddy; Boutry, Nathalie; Turck, Dominique; Duhamel, Alain; Amzallag-Bellenger, Elisa

2016-01-01

To evaluate prospectively the performance of diffusion-weighted imaging (DWI) for the detection of active lesions on MR enterography (MRE) in children with inflammatory bowel disease (IBD). MRE of 48 children (mean age 13 years) with suspected or known IBD were blindly analysed by 2 independent readers for the presence of active lesions. Two sets of imaging including DWI and gadolinium-enhanced imaging (GEI) were reviewed. A reader consensus was obtained. The gold standard was histopathological findings. In patient-level analysis and segment-level analysis, sensitivity and specificity were calculated for DWI and GEI and compared using McNemar's test or logistic random-effects models. At least 1 active lesion was confirmed in 42 (87.5%) children. Sensitivity and specificity for the detection of at least one lesion were 88.1% (95% CI, 74.3-96.1) and 83.3% (95% CI, 35.9-99.6), respectively, for DWI and 66.7% (95% CI, 50.4-80.4) and 83.3% (95% CI, 35.9-99.6), respectively, for GEI. In segment-level analysis, sensitivity and specificity for the detection of specific segment lesions were 62.5% (95% CI, 48.1-75) and 97.1% (95% CI, 93.5-98.7), respectively, for DWI and 45.7% (95% CI, 30.8-61.3) and 98.2% (95% CI, 95.3-99.4), respectively, for GEI. The sensitivity of DWI was significantly better than that of GEI per patient (p = 0.004) and per segment (p = 0.028). DWI demonstrates better performance than GEI for the detection of active lesions in children with IBD. Examination with no intravenous injection-DWI can replace T1 weighted images when paediatric patients are screened with MRE for IBD. Examination performed in free breathing is better tolerated by children.

COL1A1 transgene expression in stably transfected osteoblastic cells. Relative contributions of first intron, 3'-flanking sequences, and sequences derived from the body of the human COL1A1 minigene

NASA Technical Reports Server (NTRS)

Breault, D. T.; Lichtler, A. C.; Rowe, D. W.

1997-01-01

Collagen reporter gene constructs have be used to identify cell-specific sequences needed for transcriptional activation. The elements required for endogenous levels of COL1A1 expression, however, have not been elucidated. The human COL1A1 minigene is expressed at high levels and likely harbors sequence elements required for endogenous levels of activity. Using stably transfected osteoblastic Py1a cells, we studied a series of constructs (pOBColCAT) designed to characterize further the elements required for high level of expression. pOBColCAT, which contains the COL1A1 first intron, was expressed at 50-100-fold higher levels than ColCAT 3.6, which lacks the first intron. This difference is best explained by improved mRNA processing rather than a transcriptional effect. Furthermore, variation in activity observed with the intron deletion constructs is best explained by altered mRNA splicing. Two major regions of the human COL1A1 minigene, the 3'-flanking sequences and the minigene body, were introduced into pOBColCAT to assess both transcriptional enhancing activity and the effect on mRNA stability. Analysis of the minigene body, which includes the first five exons and introns fused with the terminal six introns and exons, revealed an orientation-independent 5-fold increase in CAT activity. In contrast the 3'-flanking sequences gave rise to a modest 61% increase in CAT activity. Neither region increased the mRNA half-life of the parent construct, suggesting that CAT-specific mRNA instability elements may serve as dominant negative regulators of stability. This study suggests that other sites within the body of the COL1A1 minigene are important for high expression, e.g. during periods of rapid extracellular matrix production.

Activation of Sphingolipid Pathway in the Livers of Lipodystrophic Agpat2−/− Mice

PubMed Central

Sankella, Shireesha; Garg, Abhimanyu

2017-01-01

A several fold increase in triacylglycerol is observed in the livers of lipodystrophic Agpat2−/− mice. We have previously reported an unexpected increase in the phosphatidic acid (PA) levels in the livers of these mice and that a few specific molecular species of PA were able to transcriptionally upregulate hepatic gluconeogenesis. In the current study, we measured the metabolites and expression of associated enzymes of the sphingolipid synthesis pathway. The entire sphingolipid pathway was activated both at the gene expression and the metabolite level. The levels of some ceramides were increased by as much as ~eightfold in the livers of Agpat2−/− mice. Furthermore, several molecular species of ceramides were increased in the plasma of Agpat2−/− mice, specifically ceramide C16:0, which was threefold elevated in the plasma of both the sexes. However, the ceramides failed to increase glucose production in mouse primary hepatocytes obtained from wild-type and Agpat2−/− mice, further establishing the specificity of PA in the induction of hepatic gluconeogenesis. This study shows elevated levels of sphingolipids in the steatotic livers of Agpat2−/− mice and increased expression of associated enzymes for the sphingolipid pathway. Therefore, this study and those in the literature suggest that ceramide C16:0 could be used as a biomarker for insulin resistance/type 2 diabetes mellitus. PMID:29264548

Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: Ex Vivo bioadhesion and in Vivo immunity.

PubMed

Li, KeXin; Zhao, Xiuli; Xu, Shiyi; Pang, DaHai; Yang, ChunRong; Chen, DaWei

2011-01-01

The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines.

Neurite-specific Ca2+ dynamics underlying sound processing in an auditory interneurone.

PubMed

Baden, T; Hedwig, B

2007-01-01

Concepts on neuronal signal processing and integration at a cellular and subcellular level are driven by recording techniques and model systems available. The cricket CNS with the omega-1-neurone (ON1) provides a model system for auditory pattern recognition and directional processing. Exploiting ON1's planar structure we simultaneously imaged free intracellular Ca(2+) at both input and output neurites and recorded the membrane potential in vivo during acoustic stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed the onset spike rate of ON1, while the final Ca(2+) level depended on the mean spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations and only gradually in the axon and the cell body. Ca(2+) levels were particularly high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive K(+) current this may exhibit a specific control over the cell's electrical response properties. In all cellular compartments presentation of species-specific calling song caused distinct oscillations of the Ca(2+) level in the chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated hyperpolarization of ON1 suppressed background spike activity between chirps, acting as a noise filter. During directional auditory processing, the functional interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition was demonstrated. Upon stimulation with different sound frequencies, the dendrites, but not the axonal arborizations, demonstrated a tonotopic response profile. This mirrored the dominance of the species-specific carrier frequency and resulted in spatial filtering of high frequency auditory inputs. (c) 2006 Wiley Periodicals, Inc.

Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized Antioxidant Nutritive Strategy.

PubMed

Lavoie, Jean-Claude; Tremblay, André

2018-03-27

Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation at birth and the sex of the infant. However, the link between sex and oxidative stress remains unclear. The aim of this study was to find a common denominator explaining the discrepancy between studies related to sex-specific effects of oxidative stress. Results highlight a specificity of sex in the levels of oxidative stress markers linked to the metabolism of glutathione, as measured in the intracellular compartments. Levels of all sex-dependent oxidative stress markers are greater and markers associated to a better antioxidant defense are lower in boys compared to girls during the neonatal period. This sex-specific discrepancy is likely to be related to estrogen metabolism, which is more active in baby-girls and promotes the activation of glutathione metabolism. our observations suggest that nutritive antioxidant strategies need to target glutathione metabolism and, therefore, should be personalized considering, among others, the sex specificity.

The Cellular and Molecular Mechanisms for Neutropenia in Barth Syndrome

PubMed Central

Makaryan, Vahagn; Kulik, Willem; Vaz, Frederic M.; Allen, Christopher; Dror, Yigal; Dale, David C.; Aprikyan, Andranik A.

2015-01-01

Barth syndrome (BTHS), a rare, X-linked, recessive disease characterized by neutropenia and cardiomyopathy. BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60 myeloid progenitor cells with TAZ-specific shRNAs. Results demonstrate a significant down-regulation in TAZ expression, mimicking the effects of naturally-occurring truncation mutations in TAZ. Flow cytometry analyses of cells with TAZ-specific, but not scrambled, shRNAs demonstrate nearly two-fold increase in proportion of annexin-V positive cells and significantly increased dissipation of mitochondrial membrane potential as determined by DIOC6-staining. Transfection of TAZ specific shRNA had similar effects in U937 myeloid cells but not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells revealed aberrant release of cytochrome c from mitochondria and significantly elevated levels of activated caspase-3 in response to TAZ knock-down. Treatment with caspase-specific inhibitor zVAD-fmk resulted in substantially reduced apoptosis to near-normal levels. These data suggest that neutropenia in BTHS is attributable to increased dissipation of mitochondrial membrane potential, aberrant release of cytochrome c, activation of caspase-3 and accelerated apoptosis of myeloid progenitor cells, and that this defect can be partially restored in vitro by treatment with caspase-specific inhibitors. PMID:22023389

/sup 125/I-Clq-binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis

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

Moss, R.B.; Hsu, Y.P.; Lewiston, N.J.

1981-08-01

We studied the incidence and levels of circulating immune complexes by the /sup 125/I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associatedmore » with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease.« less

The Effect of Deployment on Cholesterol Levels of Active Duty Personnel

DTIC Science & Technology

2006-05-01

fairly good results regarding cholesterol levels. It was noted that several members returned from deployment with elevated levels, sometimes to the...LDL cholesterol and low HDL cholesterol (Downs, John R., Beere, Polly A., Whitney, Edwin, Clearfield, Michael, Weis, Stephen, Rochen, Jeffrey, Stein...specific ages, including cholesterol screenings beginning at age 25. Given the age of the majority of this population, one might expect relatively good

A screen for over-secretion of proteins by yeast based on a dual component cellular phosphatase and immuno-chromogenic stain for exported bacterial alkaline phosphatase reporter

PubMed Central

2013-01-01

Background To isolate over-secretors, we subjected to saturation mutagenesis, a strain of P.pastoris exporting E. coli alkaline phosphatase (EAP) fused to the secretory domain of the yeast α factor pheromone through cellular PHO1/KEX2 secretory processing signals as the α-sec-EAP reporter protein. Direct chromogenic staining for α-sec-EAP activity is non-specific as its NBT/BCIP substrate cross-reacts with cellular phosphatases which can be inhibited with Levulinic acid. However, the parental E(P) strain only exports detectable levels of α-sec-EAP at 69 hours and not within the 36 hour period post-seeding required for effective screening with the consequent absence of a reference for secretion. We substituted the endogenous cellular phosphatase activity as a comparative reference for secretion rate and levels as well as for colony alignment while elevating specificity and sensitivity of detection of the exported protein with other innovative modifications of the immuno-chromogenic staining application for screening protein export mutants. Results Raising the specificity and utility of staining for α-sec-EAP activity required 5 modifications including some to published methods. These included, exploitation of endogenous phosphatase activity, reduction of the cell/protein burden, establishment of the direct relation between concentrations of transcriptional inducer and exported membrane immobilized protein and concentrations of protein exported into growth media, amplification of immuno-specificity and sensitivity of detection of α-sec-EAP reporter enzyme signal and restriction of staining to optimal concentrations of antisera and time periods. The resultant immuno-chromogenic screen allows for the detection of early secretion and as little as 1.3 fold over-secretion of α-sec-EAP reporter protein by E(M) mutants in the presence of 10 fold -216 fold higher concentrations of HSA. Conclusions The modified immuno-chromogenic screen is sensitive, specific and has led to the isolation of mutants E(M) over-secreting the α-sec-EAP reporter protein by a minimum of 50 fold higher levels than that exported by non-mutagenized E(P) parental strains. Unselected proteins were also over-secreted. PMID:23602005

Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

PubMed

Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

2015-01-01

Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

Lineage-Specific Changes in Biomarkers in Great Apes and Humans

PubMed Central

Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

2015-01-01

Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. PMID:26247603

Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).

PubMed

Anichtchik, Oleg; Sallinen, Ville; Peitsaro, Nina; Panula, Pertti

2006-10-10

Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.

The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis

PubMed Central

Shifrin, Helena; Harel, Efrat; Nadler-Milbauer, Mirela; Weinstock, Marta; Srebnik, Morris

2015-01-01

A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β. It was found that P-5 decreased the levels of TNFα and the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα. PMID:25949237

Reward-based hypertension control by a synthetic brain-dopamine interface.

PubMed

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

Development and validation of a new self-report instrument for measuring sedentary behaviors and light-intensity physical activity in adults.

PubMed

Barwais, Faisal Awad; Cuddihy, Thomas F; Washington, Tracy; Tomson, L Michaud; Brymer, Eric

2014-08-01

Low levels of physical activity and high levels of sedentary behavior (SB) are major public health concerns. This study was designed to develop and validate the 7-day Sedentary (S) and Light Intensity Physical Activity (LIPA) Log (7-day SLIPA Log), a self-report measure of specific daily behaviors. To develop the log, 62 specific SB and LIPA behaviors were chosen from the Compendium of Physical Activities. Face-to-face interviews were conducted with 32 sedentary volunteers to identify domains and behaviors of SB and LIPA. To validate the log, a further 22 sedentary adults were recruited to wear the GT3x for 7 consecutive days and nights. Pearson correlations (r) between the 7-day SLIPA Log and GT3x were significant for sedentary (r = .86, P < .001), for LIPA (r = .80, P < .001). Lying and sitting postures were positively correlated with GT3x output (r = .60 and r = .64, P < .001, respectively). No significant correlation was found for standing posture (r = .14, P = .53).The kappa values between the 7-day SLIPA Log and GT3x variables ranged from 0.09 to 0.61, indicating poor to good agreement. The 7-day SLIPA Log is a valid self-report measure of SB and LIPA in specific behavioral domains.

Characterization and use of a rabbit-anti-mouse VPAC1 antibody by flow cytometry

PubMed Central

Hermann, Rebecca J.; Van der Steen, Travis; Vomhof-DeKrey, Emilie E.; Benton, Keith D.; Failing, Jarrett J.; Haring, Jodie S.; Dorsam, Glenn P.

2011-01-01

Vasoactive intestinal peptide receptor – 1 signaling in lymphocytes has been shown to regulate chemotaxis, proliferation, apoptosis and differentiation. During T cell activation, VPAC1 mRNA is downregulated, but the effect on its protein levels is less clear. A small number of studies have reported measurement of human VPAC1 by flow cytometry, but murine VPAC1 reagents are unavailable. Therefore, we set out to generate a reliable and highly specific α-mouse VPAC1 polyclonal antibody for use with flow cytometry. After successfully generating a rabbit α-VPAC1 polyclonal antibody (α-mVPAC1 pAb), we characterized its cross-reactivity and showed that it does not recognize other family receptors (mouse VPAC2 and PAC1, human VPAC1, VPAC2 and PAC1) by flow cytometry. Partial purification of the rabbit α-VPAC1 sera increased the specific-activity of the α-mVPAC1 pAb by 20-fold, and immunofluorescence microscopy (IF) confirmed a plasma membrane subcellular localization for mouse VPAC1 protein. To test the usefulness of this specific α-mVPAC1 pAb, we showed that primary, resting mouse T cells express detectable levels of VPAC1 protein, with little detectable signal from activated T cells, or CD19 B cells. These data support our previously published data showing a downregulation of VPAC1 mRNA during T cell activation. Collectively, we have established a well-characterized, and highly species specific α-mVPAC1 pAb for VPAC1 surface measurement by IF and flow cytometry. PMID:22079255

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.

Preclinical Evaluation of the Supercritical Extract of Azadirachta Indica (Neem) Leaves In Vitro and In Vivo on Inhibition of Prostate Cancer Tumor Growth

PubMed Central

Wu, Qiang; Kohli, Manish; Bergen, H. Robert; Cheville, John C.; Karnes, R. Jeffrey; Cao, Hong; Young, Charles Y.F.; Tindall, Donald J.; McNiven, Mark A.; Donkena, Krishna Vanaja

2015-01-01

Azadirachta indica, commonly known as neem, has gained worldwide prominence because of its medical properties, namely antitumor, antiviral, anti-inflammatory, antihyperglycemic, antifungal, and antibacterial activities. Despite these promising results, gaps remain in our understanding of the molecular mechanism of action of neem compounds and their potential for use in clinical trials. We investigated supercritical extract of neem leaves (SENL) for the following: molecular targets in vitro, in vivo efficacy to inhibit tumor growth, and bioactive compounds that exert antitumor activity. Treatment of LNCaP-luc2 prostate cancer cells with SENL suppressed dihydrotestosterone-induced androgen receptor and prostate-specific antigen levels. SENL inhibited integrin β1, calreticulin, and focal adhesion kinase activation in LNCaP-luc2 and PC3 prostate cancer cells. Oral administration of SENL significantly reduced LNCaP-luc2 xenograft tumor growth in mice with the formation of hyalinized fibrous tumor tissue, reduction in the prostate-specific antigen, and increase in AKR1C2 levels. To identify the active anticancer compounds, we fractionated SENL by high-pressure liquid chromatography and evaluated 16 peaks for cytotoxic activity. Four of the 16 peaks exhibited significant cytotoxic activity against prostate cancer cells. Mass spectrometry of the isolated peaks suggested the compounds with cytotoxic activity were nimbandiol, nimbolide, 2′,3′-dihydronimbolide, and 28-deoxonim-bolide. Analysis of tumor tissue and plasma samples from mice treated with SENL indicated 28-deoxonim-bolide and nimbolide as the bioactive compounds. Overall, our data revealed the bioactive compounds in SENL and suggested that the anticancer activity could be mediated through alteration in androgen receptor and calreticulin levels in prostate cancer. PMID:24674886

Physical Activity and Its Correlates among Adults in Malaysia: A Cross-Sectional Descriptive Study

PubMed Central

Cai Lian, Tam; Bonn, Gregory; Si Han, Yeoh; Chin Choo, Yap; Chee Piau, Wong

2016-01-01

Obesity and rates of non-communicable diseases linked to physical inactivity have increased dramatically in Malaysia over the past 20 years. Malaysia has also been identified as one of the least physically active countries in the world with over 60% of adults being essentially sedentary. This study examines the relationship of socio-demographic factors to physical activity among 770 adults from 3 Malaysian states. Physical activity levels were significantly related to ethnicity, gender, age, occupation and educational level. Controlling for inter-relationships among these variables; age, gender, Chinese ethnicity and education level were found to have unique effects on total physical activity, as well as moderate and vigorous exercise. As would be expected, younger people were more physically active, engaging more in both moderate and vigorous types of exercise and males were generally more active than females. Contrary to findings from many developed countries, however, more educated Malaysians were less likely to engage in all types of physical activity. Ethnic Chinese participants, and to a lesser degree Indians also consistently reported lower levels of activity. Possible intervention strategies are discussed that specifically target ethnic and cultural norms related to physical activity. Future research programs exploring barriers to participation and perceptions of physical activity, as well as programs to encourage active life styles among youths are also suggested. PMID:27332883

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

Towards an automated and efficient calculation of resonating vibrational states based on state-averaged multiconfigurational approaches

NASA Astrophysics Data System (ADS)

Meier, Patrick; Oschetzki, Dominik; Pfeiffer, Florian; Rauhut, Guntram

2015-12-01

Resonating vibrational states cannot consistently be described by single-reference vibrational self-consistent field methods but request the use of multiconfigurational approaches. Strategies are presented to accelerate vibrational multiconfiguration self-consistent field theory and subsequent multireference configuration interaction calculations in order to allow for routine calculations at this enhanced level of theory. State-averaged vibrational complete active space self-consistent field calculations using mode-specific and state-tailored active spaces were found to be very fast and superior to state-specific calculations or calculations with a uniform active space. Benchmark calculations are presented for trans-diazene and bromoform, which show strong resonances in their vibrational spectra.

Towards an automated and efficient calculation of resonating vibrational states based on state-averaged multiconfigurational approaches

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

Meier, Patrick; Oschetzki, Dominik; Pfeiffer, Florian

Resonating vibrational states cannot consistently be described by single-reference vibrational self-consistent field methods but request the use of multiconfigurational approaches. Strategies are presented to accelerate vibrational multiconfiguration self-consistent field theory and subsequent multireference configuration interaction calculations in order to allow for routine calculations at this enhanced level of theory. State-averaged vibrational complete active space self-consistent field calculations using mode-specific and state-tailored active spaces were found to be very fast and superior to state-specific calculations or calculations with a uniform active space. Benchmark calculations are presented for trans-diazene and bromoform, which show strong resonances in their vibrational spectra.

Anthropometry and physical activity level in the prediction of metabolic syndrome in children.

PubMed

Andaki, Alynne Christian Ribeiro; Tinôco, Adelson Luiz Araújo; Mendes, Edmar Lacerda; Andaki Júnior, Roberto; Hills, Andrew P; Amorim, Paulo Roberto S

2014-10-01

To evaluate the effectiveness of anthropometric measures and physical activity level in the prediction of metabolic syndrome (MetS) in children. Cross-sectional study with children from public and private schools. Children underwent an anthropometric assessment, blood pressure measurement and biochemical evaluation of serum for determination of TAG, HDL-cholesterol and glucose. Physical activity level was calculated and number of steps per day obtained using a pedometer for seven consecutive days. Viçosa, south-eastern Brazil. Boys and girls (n 187), mean age 9·90 (SD 0·7) years. Conicity index, sum of four skinfolds, physical activity level and number of steps per day were accurate in predicting MetS in boys. Anthropometric indicators were accurate in predicting MetS for girls, specifically BMI, waist circumference measured at the narrowest point and at the level of the umbilicus, four skinfold thickness measures evaluated separately, the sum of subscapular and triceps skinfold thickness, the sum of four skinfolds and body fat percentage. The sum of four skinfolds was the most accurate method in predicting MetS in both genders.

Sensitive and specific detection of classical scrapie prions in the brain of goats by real-time quaking-induced conversion

USDA-ARS?s Scientific Manuscript database

The real-time quaking-induced conversion (RT-QuIC) is a rapid, specific, and sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect sub-infectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully us...

Measuring mitochondrial uncoupling protein-2 level and activity in insulinoma cells.

PubMed

Barlow, Jonathan; Hirschberg, Verena; Brand, Martin D; Affourtit, Charles

2013-01-01

Mitochondrial uncoupling protein-2 (UCP2) regulates glucose-stimulated insulin secretion (GSIS) by pancreatic beta cells-the physiological role of the beta cell UCP2 remains a subject of debate. Experimental studies informing this debate benefit from reliable measurements of UCP2 protein level and activity. In this chapter, we describe how UCP2 protein can be detected in INS-1 insulinoma cells and how it can be knocked down by RNA interference. We demonstrate briefly that UCP2 knockdown lowers glucose-induced rises in mitochondrial respiratory activity, coupling efficiency of oxidative phosphorylation, levels of mitochondrial reactive oxygen species, and insulin secretion. We provide protocols for the detection of the respective UCP2 phenotypes, which are indirect, but invaluable measures of UCP2 activity. We also introduce a convenient method to normalize cellular respiration to cell density allowing measurement of UCP2 effects on specific mitochondrial oxygen consumption. Copyright © 2013 Elsevier Inc. All rights reserved.

High-School Students' Reasoning while Constructing Plant Growth Models in a Computer-Supported Educational Environment. Research Report

ERIC Educational Resources Information Center

Ergazaki, Marida; Komis, Vassilis; Zogza, Vassiliki

2005-01-01

This paper highlights specific aspects of high-school students' reasoning while coping with a modeling task of plant growth in a computer-supported educational environment. It is particularly concerned with the modeling levels ('macro-phenomenological' and 'micro-conceptual' level) activated by peers while exploring plant growth and with their…

Exploration of the influence of self-efficacy on recreation participation levels of individuals with visual impairments who use dog guides

Treesearch

Laurlyn K. Harmon; Linda L. Caldwell

2002-01-01

Self-efficacy and its relationship to outdoor recreation is only recently being explored. This paper is an attempt to identify the specific domain of leisure self-efficacy and to explore how it might be related to participation levels in outdoor recreation activities of individuals with visual impairments.

Awareness is relative: dissociation as the organisation of meaning.

PubMed

Lesley, Joan

2006-09-01

This essay discusses how the organisation of mental material within the cognitive system can influence consciousness and awareness, and presents a theory of dissociation based on the premise that awareness is relative, contingent on the activated representation of the ongoing event being linked to the activated self-representation. It allows four possible variations of integration: (i) non-integrated experience--perceptions about an object/event are either not perceived or they remain at the sensory level: traditional dissociative states, amnesia, depersonalisation etc; (ii) variably integrated experience--activation of information of a specific valence about an object blocks activation of information of contrasting valence: splitting; (iii) alternatively integrated experience--experience is integrated into a specific, limited active self-representation: fugue and multiple identity states; (iv) dis-integrated experience-the ongoing experience of innate drives and needs is no longer consistently activated in the core self-representation: repression and isolation.

Physical activity and neuropsychiatric symptoms of Parkinson disease.

PubMed

Abrantes, Ana M; Friedman, Joseph H; Brown, Richard A; Strong, David R; Desaulniers, Julie; Ing, Eileen; Saritelli, Jennifer; Riebe, Deborah

2012-09-01

Neuropsychiatric symptoms of Parkinson disease (PD) such as fatigue, depression, and apathy are common and detract from quality of life. There is little published on the impact of physical activity on the neuropsychiatric symptoms of PD. A convenience sample of 45 patients with PD (mean age = 66.1 years; 33% female) completed questionnaires on physical activity, neuropsychiatric symptoms, and specific exercise preferences. Covarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect. Exercise preferences included moderate intensity (73%), at home (56%), in the morning (73%), scheduled (69%), options for varied activities (73%), and preference for both structured/supervised (50%), and unsupervised/self-paced (50%) programs. Preferred activities included the use of aerobic exercise equipment, resistance training, and yoga. Developing and tailoring exercise programs that incorporate specific preferences may result in more effective interventions for patients with PD.

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

PubMed

Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

2016-11-01

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

Microbial responses to multi-factor climate change: effects on soil enzymes.

PubMed

Steinweg, J Megan; Dukes, Jeffrey S; Paul, Eldor A; Wallenstein, Matthew D

2013-01-01

The activities of extracellular enzymes, the proximate agents of decomposition in soils, are known to depend strongly on temperature, but less is known about how they respond to changes in precipitation patterns, and the interaction of these two components of climate change. Both enzyme production and turnover can be affected by changes in temperature and soil moisture, thus it is difficult to predict how enzyme pool size may respond to altered climate. Soils from the Boston-Area Climate Experiment (BACE), which is located in an old field (on abandoned farmland), were used to examine how climate variables affect enzyme activities and microbial biomass carbon (MBC) in different seasons and in soils exposed to a combination of three levels of precipitation treatments (ambient, 150% of ambient during growing season, and 50% of ambient year-round) and four levels of warming treatments (unwarmed to ~4°C above ambient) over the course of a year. Warming, precipitation and season had very little effect on potential enzyme activity. Most models assume that enzyme dynamics follow microbial biomass, because enzyme production should be directly controlled by the size and activity of microbial biomass. We observed differences among seasons and treatments in mass-specific potential enzyme activity, suggesting that this assumption is invalid. In June 2009, mass-specific potential enzyme activity, using chloroform fumigation-extraction MBC, increased with temperature, peaking under medium warming and then declining under the highest warming. This finding suggests that either enzyme production increased with temperature or turnover rates decreased. Increased maintenance costs associated with warming may have resulted in increased mass-specific enzyme activities due to increased nutrient demand. Our research suggests that allocation of resources to enzyme production could be affected by climate-induced changes in microbial efficiency and maintenance costs.

Global- and renal-specific sympathoinhibition in aldosterone hypertension.

PubMed

Lohmeier, Thomas E; Liu, Boshen; Hildebrandt, Drew A; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

2015-06-01

Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. © 2015 American Heart Association, Inc.

Global and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

PubMed Central

Lohmeier, Thomas E.; Liu, Boshen; Hildebrandt, Drew A.; Cates, Adam W.; Georgakopoulos, Dimitrios; Irwin, Eric D.

2015-01-01

Recent technology for chronic electrical activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12µg/kg/day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ~ 40% and arterial pressure by 16±2 mmHg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mmHg) was diminished (~ 55%) during aldosterone hypertension as compared to control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

A simple PCR-based strategy for estimating species-specific contributions in chimeras and xenografts

PubMed Central

Ealba, Erin L.; Schneider, Richard A.

2013-01-01

Many tissue-engineering approaches for repair and regeneration involve transplants between species. Yet a challenge is distinguishing donor versus host effects on gene expression. This study provides a simple molecular strategy to quantify species-specific contributions in chimeras and xenografts. Species-specific primers for reverse transcription quantitative real-time PCR (RT-qPCR) were designed by identifying silent mutations in quail, duck, chicken, mouse and human ribosomal protein L19 (RPL19). cDNA from different pairs of species was mixed in a dilution series and species-specific RPL19 primers were used to generate standard curves. Then quail cells were transplanted into transgenic-GFP chick and resulting chimeras were analyzed with species-specific primers. Fluorescence-activated cell sorting (FACS) confirmed that donor- and host-specific levels of RPL19 expression represent actual proportions of cells. To apply the RPL19 strategy, we measured Runx2 expression in quail-duck chimeras. Elevated Runx2 levels correlated with higher percentages of donor cells. Finally, RPL19 primers also discriminated mouse from human and chick. Thus, this strategy enables chimeras and/or xenografts to be screened rapidly at the molecular level. PMID:23785056

What's Going on in Your Professor's Head? Demonstrating the Id, Ego, and Superego

ERIC Educational Resources Information Center

Segrist, Dan J.

2009-01-01

This article describes an in-class activity designed to demonstrate Freud's structural theory of the psyche, specifically the roles of the id, ego, and superego, as well as the interplay among them. Additionally, the activity visually illustrates Freud's ideas about the levels of consciousness associated with these 3 components. Pre-post quiz…

Overcoming the Influence of Chronic Pain on Older Patients' Difficulty with Recommended Self-Management Activities

ERIC Educational Resources Information Center

Krein, Sarah L.; Heisler, Michele; Piette, John D.; Butchart, Amy; Kerr, Eve A.

2007-01-01

Purpose: Many older patients with common chronic conditions also experience chronic pain. We examined how chronic pain affects patients' difficulty with recommended self-management activities and the potential intervening role of self-efficacy (the level of confidence in one's own ability to perform a specific task). Design and Methods: We…

Young Scientists Explore the Human Body. Book 11 Primary Level.

ERIC Educational Resources Information Center

Penn, Linda

Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. The activities specifically focus on the human body and encourage a positive self-concept. The theme of the first section is air--the breath of…

Underage Females' Experiences of Sexual Relations, Motherhood, and Married Life

ERIC Educational Resources Information Center

Gurko, T.A.

2004-01-01

In this article, the author discusses the social issues that concern the young adolescents in Russia and their early onset to sexual activity. The early onset of sexual activity among adolescents in Russia is taking place under conditions that are quite specific. These conditions include: a low level of contraceptive awareness, a very small number…

Actively Controlled Magnetic Vibration-Isolation System

NASA Technical Reports Server (NTRS)

Grodsinky, Carlos M.; Logsdon, Kirk A.; Wbomski, Joseph F.; Brown, Gerald V.

1993-01-01

Prototype magnetic suspension system with active control isolates object from vibrations in all six degrees of freedom at frequencies as low as 0.01 Hz. Designed specifically to protect instruments aboard spacecraft by suppressing vibrations to microgravity levels; basic control approach used for such terrestrial uses as suppression of shocks and other vibrations in trucks and railroad cars.

Isozvme specificity during germination and early growth of knobcone pine

Treesearch

M. Thompson Conkle

1971-01-01

Five enzyme classes from 11 developmental stages of germinating embryos were separated by starch gel electrophoresis. Alcohol dehydrogenase isozymes found in embryos of dry seed were most active at the time of radicle emergence; activity decreased thereafter, fading below the level of detection when seed coats were shed. Peroxidase isozymes were absent and esterase...

Association and Diffusion of Nutrition and Physical Activity Policies on the State and District Level

ERIC Educational Resources Information Center

Taber, Daniel R.; Chriqui, Jamie F.; Chaloupka, Frank J.

2012-01-01

Background: School district wellness policies designed to reduce obesity and promote student health and well-being often lack specific requirements or any mandate that schools comply with the policy. Researchers, educators, and policymakers have called for states to take an active role in shaping district policies. The objective of this study was…

Task Design and Skill Level Perceptions of Middle School Students toward Competition in Dance-Related Active Gaming

ERIC Educational Resources Information Center

Bernstein, Eve; Gibbone, Anne; Rukavina, Paul

2015-01-01

In this study, we drew upon McCaughtry, Tischler, and Flory's (2008) reconceptualized ecological framework to examine middle school students' perceptions (N = 391) of competition in physical education, specifically after participating in noncompetitive and competitive active gaming (AG) sessions. Chi-square tests of independence were computed on…

Suggestions for Teaching Mathematics Using Laboratory Approaches Grades 1-6. 4. Measurement. Experimental Edition.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Elementary Curriculum Development.

This guide describes activities and materials which can be used in a mathematics laboratory approach to a basic mathematics program for grades 1-6. One-hundred thirteen activities pertaining to measurement concepts are described in terms of purpose, suggested grade levels, materials needed, and procedures. Some specific concepts include: linear…

BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination.

PubMed

Shim, Do-Wan; Shin, Woo-Young; Yu, Sang-Hyeun; Kim, Byung-Hak; Ye, Sang-Kyu; Koppula, Sushruta; Won, Hyung-Sik; Kang, Tae-Bong; Lee, Kwang-Ho

2017-11-08

The ATPase activity of NLRP3 has pivotal role in inflammasome activation and is recognized as a good target for the development of the NLRP3 inflammasome-specific inhibitor. However, signals in the vicinity of the ATPase activity of NLRP3 have not been fully elucidated. Here, we demonstrate NLRP3 inflammasome-specific action of a benzoxathiole derivative, BOT-4-one. BOT-4-one exhibited an inhibition of NLRP3 inflammasome activation, which was attributable to its alkylating capability to NLRP3. In particular, the NLRP3 alkylation by BOT-4-one led to an impaired ATPase activity of NLRP3, thereby obstructing the assembly of the NLRP3 inflammasome. Additionally, we found that NLRP3 alkylators, including BOT-4-one, enhance the ubiquitination level of NLRP3, which might also contribute to the inhibition of NLRP3 inflammasome activation. Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.

Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.

PubMed

Leasure, J Leigh; Giddabasappa, Anand; Chaney, Shawntay; Johnson, Jerry E; Pothakos, Konstantinos; Lau, Yuen Sum; Fox, Donald A

2008-03-01

Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Our goals were to establish a murine model of human equivalent GLE and to determine dose-response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Peak [BPb] were < 1, < or = 10, 24-27, and 33-42 microg/dL in control, low-, moderate- and high-dose GLE groups at PN0-10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose-response toxicant exposure should be a component of the neurotoxic risk assessment process.

Low-Level Human Equivalent Gestational Lead Exposure Produces Sex-Specific Motor and Coordination Abnormalities and Late-Onset Obesity in Year-Old Mice

PubMed Central

Leasure, J. Leigh; Giddabasappa, Anand; Chaney, Shawntay; Johnson, Jerry E.; Pothakos, Konstantinos; Lau, Yuen Sum; Fox, Donald A.

2008-01-01

Background Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Objectives Our goals were to establish a murine model of human equivalent GLE and to determine dose–response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. Methods We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Results Peak [BPb] were < 1, ≤ 10, 24–27, and 33–42 μg/dL in control, low-, moderate- and high-dose GLE groups at PN0–10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Conclusions Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose–response toxicant exposure should be a component of the neurotoxic risk assessment process. PMID:18335103

Perceived Neighborhood Environment and Walking for Specific Purposes Among Elderly Japanese

PubMed Central

Inoue, Shigeru; Ohya, Yumiko; Odagiri, Yuko; Takamiya, Tomoko; Kamada, Masamitsu; Okada, Shinpei; Oka, Kohichiro; Kitabatake, Yoshinori; Nakaya, Tomoki; Sallis, James F; Shimomitsu, Teruichi

2011-01-01

Background Recent research has revealed the importance of neighborhood environment as a determinant of physical activity. However, evidence among elderly adults is limited. This study examined the association between perceived neighborhood environment and walking for specific purposes among Japanese elderly adults. Methods This population-based, cross-sectional study enrolled 1921 participants (age: 65–74 years, men: 51.9%). Neighborhood environment (International Physical Activity Questionnaire Environmental Module) and walking for specific purposes (ie, transportation or recreation) were assessed by self-report. Multilevel logistic regression analyses with individuals at level 1 and neighborhoods at level 2 were conducted to examine the association between environment and walking, after adjustment for potential confounders. Results Access to exercise facilities, social environment, and aesthetics were associated with total neighborhood walking. Odds ratios (95% CI) were 1.23 (1.00–1.51), 1.39 (1.14–1.71), and 1.48 (1.21–1.81), respectively. Regarding walking for specific purposes, social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Environmental correlates differed by specific types of walking and by sex. Transportation walking significantly correlated with a greater variety of environmental attributes. Sex differences were observed, especially for transportation walking. Bicycle lanes, crime safety, traffic safety, aesthetics, and household motor vehicles were significant correlates among men, while access to shops, access to exercise facilities, and social environment were important among women. Conclusions Specific environment–walking associations differed by walking purpose and sex among elderly adults. Social environment and aesthetics were consistent correlates of both transportation walking and recreational walking. Improving these environmental features might be effective in promoting physical activity among elderly Japanese. PMID:22001543

Are Total, Intensity- and Domain-Specific Physical Activity Levels Associated with Life Satisfaction among University Students?

PubMed Central

Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E.

2015-01-01

Background Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. Methods The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire — long form and the Satisfaction with Life Scale. Results Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001), younger age (β = -0.07; p = 0.024), higher disposable income (β = 0.10; p = 0.001), and better self-rated health (β = 0.30; p = <0.001). No significant association was found between life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). Conclusions This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading. PMID:25695492

Are total, intensity- and domain-specific physical activity levels associated with life satisfaction among university students?

PubMed

Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E

2015-01-01

Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire-long form and the Satisfaction with Life Scale. Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001), younger age (β = -0.07; p = 0.024), higher disposable income (β = 0.10; p = 0.001), and better self-rated health (β = 0.30; p = <0.001). No significant association was found between life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading.

Characterization of soluble and membrane-bound alkaline phosphatase in Nilaparvata lugens and their potential relation to development and insecticide resistance.

PubMed

Wang, Zengxia; Liu, Shuhua; Yang, Baojun; Liu, Zewen

2011-09-01

Two forms (soluble and membrane-bound) of alkaline phosphatases (ALPs) were found in the brown planthopper, Nilaparvata lugens. In order to further study ALPs in N. lugens, two putative ALP genes (Nl-ALP1 and Nl-ALP2) were identified in this pest. Both Nl-ALP1 and Nl-ALP2 show approximately the same degree of sequence identity (40-50%) to other insect soluble and membrane-bound forms of ALP. Correlation of ALP activity and mRNA levels at different developmental stages, or following application of 20-hydroxyecdysone (20E) and insecticide fenvalerate, suggests that Nl-ALP1 and Nl-ALP2 might encode a soluble (sALP) and a membrane-bound ALP (mALP), respectively. Nl-ALP1-specific antibody Nl1-I detected only a specific band in soluble protein preparations and Nl-ALP2 specific antibody Nl2-I only detected a specific band in insoluble protein preparations, which provided conclusive linkages between Nl-ALP1 and a sALP and between Nl-ALP2 and a m ALP. Then, Nl-ALP1 was denoted as Nl-sALP for a sALP and Nl-ALP2 was denoted as Nl-mALP for a mALP. Only sALP activity and Nl-sALP mRNA level were induced by 20E and fenvalerate, which was confirmed by the density of specific band detected by Nl1-I in Sus strain with or without fenvalerate treatment. Additionally, the sALP activity, as well as Nl-sALP mRNA level, was significantly higher in a fenvalerate resistant population, compared with Sus strain. These results indicate that the sALP is more responsive to chemical stimulus, such as hormone and insecticide, and might play dual roles in development and insecticide tolerance. © 2011 Wiley Periodicals, Inc.

E-ELT requirements flow down

NASA Astrophysics Data System (ADS)

Gonzalez, J. C.; Kurlandczyk, H.; Schmid, C.; Schneller, D.

2016-08-01

One of the critical activities in the systems engineering scope of work is managing requirements. In line with this, E-ELT devotes a significant effort to this activity, which follows a well-established process. This involves optimally deriving requirements from the user (Top-Level Requirements) through the system Level 1 Requirements and from here down to subsystems procurement specifications. This paper describes the process, which is illustrated with some practical examples, including in particular the role of technical budgets to derive requirements on subsystems. Also, the provisions taken for the requirements verification are discussed.

Biologically-inspired robust and adaptive multi-sensor fusion and active control

NASA Astrophysics Data System (ADS)

Khosla, Deepak; Dow, Paul A.; Huber, David J.

2009-04-01

In this paper, we describe a method and system for robust and efficient goal-oriented active control of a machine (e.g., robot) based on processing, hierarchical spatial understanding, representation and memory of multimodal sensory inputs. This work assumes that a high-level plan or goal is known a priori or is provided by an operator interface, which translates into an overall perceptual processing strategy for the machine. Its analogy to the human brain is the download of plans and decisions from the pre-frontal cortex into various perceptual working memories as a perceptual plan that then guides the sensory data collection and processing. For example, a goal might be to look for specific colored objects in a scene while also looking for specific sound sources. This paper combines three key ideas and methods into a single closed-loop active control system. (1) Use high-level plan or goal to determine and prioritize spatial locations or waypoints (targets) in multimodal sensory space; (2) collect/store information about these spatial locations at the appropriate hierarchy and representation in a spatial working memory. This includes invariant learning of these spatial representations and how to convert between them; and (3) execute actions based on ordered retrieval of these spatial locations from hierarchical spatial working memory and using the "right" level of representation that can efficiently translate into motor actions. In its most specific form, the active control is described for a vision system (such as a pantilt- zoom camera system mounted on a robotic head and neck unit) which finds and then fixates on high saliency visual objects. We also describe the approach where the goal is to turn towards and sequentially foveate on salient multimodal cues that include both visual and auditory inputs.

Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis.

PubMed

Lenzo, Jason C; O'Brien-Simpson, Neil M; Orth, Rebecca K; Mitchell, Helen L; Dashper, Stuart G; Reynolds, Eric C

2016-09-01

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis

PubMed Central

Lenzo, Jason C.; O'Brien-Simpson, Neil M.; Orth, Rebecca K.; Mitchell, Helen L.; Dashper, Stuart G.

2016-01-01

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals—P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa—for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis. Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals. PMID:27354442

Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

PubMed Central

Stronks, Dirk L.; Dik, Willem A.; Schreurs, Marco W. J.

2017-01-01

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p < 0.001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS. PMID:28634419

Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity*S⃞

PubMed Central

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P.; Lewis, Timothy A.; Maglathin, Rebecca L.; McLean, Thomas H.; Bochkarev, Alexey; Plotnikov, Alexander N.; Vedadi, Masoud; Arrowsmith, Cheryl H.

2008-01-01

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators. PMID:18285338

Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

PubMed

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P; Lewis, Timothy A; Maglathin, Rebecca L; McLean, Thomas H; Bochkarev, Alexey; Plotnikov, Alexander N; Vedadi, Masoud; Arrowsmith, Cheryl H

2008-04-25

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

Increased experience amplifies the activation of task-irrelevant category representations.

PubMed

Wu, Rachel; Pruitt, Zoe; Zinszer, Benjamin D; Cheung, Olivia S

2017-02-01

Prior research has demonstrated the benefits (i.e., task-relevant attentional selection) and costs (i.e., task-irrelevant attentional capture) of prior knowledge on search for an individual target or multiple targets from a category. This study investigated whether the level of experience with particular categories predicts the degree of task-relevant and task-irrelevant activation of item and category representations. Adults with varying levels of dieting experience (measured via 3 subscales of Disinhibition, Restraint, Hunger; Stunkard & Messick, Journal of Psychosomatic Research, 29(1), 71-83, 1985) searched for targets defined as either a specific food item (e.g., carrots), or a category (i.e., any healthy or unhealthy food item). Apart from the target-present trials, in the target-absent "foil" trials, when searching for a specific item (e.g., carrots), irrelevant items from the target's category (e.g., squash) were presented. The ERP (N2pc) results revealed that the activation of task-relevant representations (measured via Exemplar and Category N2pc amplitudes) did not differ based on the degree of experience. Critically, however, increased dieting experience, as revealed by lower Disinhibition scores, predicted activation of task-irrelevant representations (i.e., attentional capture of foils from the target item category). Our results suggest that increased experience with particular categories encourages the rapid activation of category representations even when category information is task irrelevant, and that the N2pc in foil trials could potentially serve as an indication of experience level in future studies on categorization.

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

Methods for measuring serum activity levels of the 192 Q and R isoenzymes of paraoxonase 1 in QR heterozygous individuals.

PubMed

Teiber, John F; Kramer, Gerald L; Haley, Robert W

2013-08-01

Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). The Q and R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays. We determined PON1 Q192R genotypes with PCR and Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to the Q isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100 - %Q. We estimated Q and R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by %Q and %R. In all 2095 samples, the PXN/AE and PXN/DZN ratios predicted Q192R phenotypes with nearly identical accuracy (κ = 0.997). In the 925 QR heterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%. These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.

Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.

PubMed

Kil, In Sup; Lee, Young Sup; Bae, Young Seuk; Huh, Tae Lin; Park, Jeen-Woo

2004-01-01

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP(+)-specific isocitrate dehydrogenases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fed rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.

Formaldehyde activation of mitoxantrone yields CpG and CpA specific DNA adducts

PubMed Central

Parker, Belinda S.; Cutts, Suzanne M.; Cullinane, Carleen; Phillips, Don R.

2000-01-01

Recently we have found that mitoxantrone, like Adriamycin, can be activated by formaldehyde and subsequently form adducts which stabilise double-stranded DNA in vitro. This activation by formaldehyde may be biologically relevant since formaldehyde levels are elevated in those tumours in which mitoxantrone is most cytotoxic. In vitro transcription analysis revealed that these adducts block the progression of RNA polymerase during transcription and cause truncated RNA transcripts. There was an absolute requirement for both mitoxantrone and formaldehyde in transcriptional blockage formation and the activated complex was found to exhibit site specificity, with blockage occurring prior to CpG and CpA sites in the DNA (non-template strand). The stability of the adduct at 37°C was site dependent. The half-lives ranged from 45 min to ~5 h and this was dependent on both the central 2 bp blockage site as well as flanking sequences. The CpG specificity of mitoxantrone adduct sites was also confirmed independently by a λ exonuclease digestion assay. PMID:10648792

Does the Sound of a Barking Dog Activate its Corresponding Visual Form? An fMRI Investigation of Modality-Specific Semantic Access

PubMed Central

Reilly, Jamie; Garcia, Amanda; Binney, Richard J.

2016-01-01

Much remains to be learned about the neural architecture underlying word meaning. Fully distributed models of semantic memory predict that the sound of a barking dog will conjointly engage a network of distributed sensorimotor spokes. An alternative framework holds that modality-specific features additionally converge within transmodal hubs. Participants underwent functional MRI while covertly naming familiar objects versus newly learned novel objects from only one of their constituent semantic features (visual form, characteristic sound, or point-light motion representation). Relative to the novel object baseline, familiar concepts elicited greater activation within association regions specific to that presentation modality. Furthermore, visual form elicited activation within high-level auditory association cortex. Conversely, environmental sounds elicited activation in regions proximal to visual association cortex. Both conditions commonly engaged a putative hub region within lateral anterior temporal cortex. These results support hybrid semantic models in which local hubs and distributed spokes are dually engaged in service of semantic memory. PMID:27289210

The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo.

PubMed

Bueno, O F; De Windt, L J; Lim, H W; Tymitz, K M; Witt, S A; Kimball, T R; Molkentin, J D

2001-01-19

Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

PubMed Central

Njoku, Dolores B.; Mellerson, Jenelle L.; Talor, Monica V.; Kerr, Douglas R.; Faraday, Nauder R.; Outschoorn, Ingrid; Rose, Noel R.

2006-01-01

Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q- and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation. PMID:16467335

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.

Relations among water levels, specific conductance, and depths of bedrock fractures in four road-salt-contaminated wells in Maine, 2007–9

USGS Publications Warehouse

Schalk, Charles W.; Stasulis, Nicholas W.

2012-01-01

Data on groundwater-level, specific conductance (a surrogate for chloride), and temperature were collected continuously from 2007 through 2009 at four bedrock wells known to be affected by road salts in an effort to determine the effects of road salting and fractures in bedrock that intersect the well at a depth below the casing on the presence of chloride in groundwater. Dissolved-oxygen data collected periodically also were used to make inferences about the interaction of fractures and groundwater flow. Borehole geophysical tools were used to determine the depths of fractures in each well that were actively contributing flow to the well, under both static and pumped conditions; sample- and measurement-depths were selected to correspond to the depths of these active fractures. Samples of water from the wells, collected at depths corresponding to active bedrock fractures, were analyzed for chloride concentration and specific conductance; from these analyses, a linear relation between chloride concentration and specific conductance was established, and continuous and periodic measurements of specific conductance were assumed to represent chloride concentration of the well water at the depth of measurement. To varying degrees, specific conductance increased in at least two of the wells during winter and spring thaws; the shallowest well, which also was closest to the road receiving salt treatment during the winter, exhibited the largest changes in specific conductance during thaws. Recharge events during summer months, long after application of road salt had ceased for the year, also produced increases in specific conductance in some of the wells, indicating that chloride which had accumulated or sequestered in the overburden was transported to the wells throughout the year. Geophysical data and periodic profiles of water quality along the length of each well’s borehole indicated that the greatest changes in water quality were associated with active fractures; in one case, high concentration of dissolved oxygen at the bottom of the well indicated the presence of a highly transmissive fracture that was in good connection with a surficial feature (stream or atmosphere). Data indicated that fractures have a substantial influence on the transport of chlorides to the subsurface; that elevated specific conductance occurred throughout the year, not just when road salts were applied; and that chloride contamination, as indicated by elevated specific conductance, may persist for years.

Ocular surface inflammation, and nerve growth factor level in tears in active thyroid-associated ophthalmopathy.

PubMed

Yoon, Jin Sook; Choi, Soo Hyun; Lee, Joon H; Lee, Sung Jun; Lee, Sang Yeul

2010-02-01

To measure tear nerve growth factor (NGF) concentrations in cases of active thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid treatment, and to correlate NGF levels with disease inflammatory activity and thyroid autoantibody concentration. The study involved 20 patients with active TAO and 20 age- and gender-matched controls. Tear break-up time (BUT) was obtained, the Schirmer test was performed, and tear NGF/total protein ratio was measured in control subjects and patients with active TAO before, and 2 and 4 weeks after, steroid treatment. Tear BUT and Schirmer values significantly increased after 2 and 4 weeks of steroid treatment (p < 0.001 and p = 0.004 respectively). Baseline tear NGF/total protein ratio was higher in patients with active TAO than in control subjects, and the ratio significantly decreased after 2 and 4 weeks of steroid treatment (p < 0.001). Tear NGF/total protein ratio did not correlate with inflammatory activity score, exophthalmos value and thyroid binding inhibiting immunoglobulin (TBII) level (p > 0.05). Tear NGF may have a specific role in ocular surface inflammation, which protects against ocular surface damage in patients with active TAO. Anti-inflammatory treatment significantly reduced the level of NGF in tears, increased tear film stability and production, and decreased congestive symptoms.

Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology

PubMed Central

Bentley, William J.; Li, Jingfeng M.; Snyder, Abraham Z.; Raichle, Marcus E.; Snyder, Lawrence H.

2016-01-01

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these “task-negative” BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process. PMID:25385710

Quality of life and physical activity in a sample of Brazilian older adults.

PubMed

Guedes, Dartagnan P; Hatmann, Angélica C; Martini, Fábio Antônio N; Borges, Marcelo B; Bernardelli, Rinaldo

2012-03-01

To investigate the association between physical activity and quality of life in a sample of Brazilian older adults. The Portuguese version of the World Health Organization Quality of Life Instrument-Older Adults Module and International Physical Activity Questionnaire was administered to 1,204 subjects (645 women and 559 men) aged ≥ 60 years. Older adults of both genders who reported to be more physically active attributed higher scores to the sensory ability, autonomy, and intimacy domains, in addition to presenting significantly higher overall quality of life, irrespectively of age, marital status, educational level, and socioeconomic status. Specifically in women, the scores obtained for the social participation domain were significantly higher in the strata of active and very active subjects when compared to sedentary subjects. The results indicate that increases in the levels of physical activity can contribute to improvements in quality of life of older adults.

Glutathione S-transferase π complexes with and stimulates Na⁺,K⁺-ATPase.

PubMed

Ochiai, Hideo; Eguchi, Hiroshi; Noguchi, Shunsuke; Hayashi, Yutaro; Nishino, Hideaki; Kawamura, Masaru; Wu, Chau H

2013-01-01

Glutathione S-transferase (GST) was found to complex with the Na⁺,K⁺-ATPase as shown by binding assay using quartz crystal microbalance. The complexation was obstructed by the addition of antiserum to the α-subunit of the Na⁺,K⁺-ATPase, suggesting the specificity of complexation between GST and the Na⁺,K⁺-ATPase. Co-immunoprecipitation experiments, using the anti-α-subunit antiserum to precipitate the GST-Na⁺,K⁺-ATPase complex and then using antibodies specific to an isoform of GST to identify the co-precipitated proteins, revealed that GSTπ was complexed with the Na⁺,K⁺-ATPase. GST stimulated the Na⁺,K⁺-ATPase activity up to 1.4-fold. The level of stimulation exhibited a saturable dose-response relationship with the amount of GST added, although the level of stimulation varied depending on the content of GSTπ in the lots of GST received from supplier. The stimulation was also obtained when recombinant GSTπ was used, confirming the results. When GST was treated with reduced glutathione, GST activity was greatly stimulated, whereas the level of stimulation of the Na⁺,K⁺-ATPase activity was similar to that when untreated GST was added. When GST was treated with H₂O₂, GST activity was greatly diminished while the stimulation of the Na⁺,K⁺-ATPase activity was preserved. The results suggest that GSTπ complexes with the Na⁺,K⁺-ATPase and stimulates the latter independent of its GST activity. Copyright © 2012 John Wiley & Sons, Ltd.

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.

Cortical preparatory activity: representation of movement or first cog in a dynamical machine?

PubMed Central

Churchland, MM; Cunningham, JP; Kaufman, MT; Ryu, SI; Shenoy, KV

2010-01-01

Summary The motor cortices are active during both movement and movement preparation. A common assumption is that preparatory activity constitutes a sub-threshold form of movement activity: a neuron active during rightwards movements becomes modestly active during preparation of a rightwards movement. We asked whether this pattern of activity is in fact observed. We found that it was not: at the level of a single neuron, preparatory tuning was weakly correlated with movement-period tuning. Yet somewhat paradoxically, preparatory tuning could be captured by a preferred direction in an abstract ‘space’ that described the population-level pattern of movement activity. In fact, this relationship accounted for preparatory responses better than did traditional tuning models. These results are expected if preparatory activity provides the initial state of a dynamical system whose evolution produces movement activity. Our results thus suggest that preparatory activity may not represent specific factors, and may instead play a more mechanistic role. PMID:21040842

Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation

PubMed Central

Ciccosanti, Fabiola

2016-01-01

Autophagy is an intracellular degradation pathway whose levels are tightly controlled to secure cell homeostasis. Unc-51–like kinase 1 (ULK1) is a conserved serine–threonine kinase that plays a central role in the initiation of autophagy. Here, we report that upon autophagy progression, ULK1 protein levels are specifically down-regulated by the E3 ligase NEDD4L, which ubiquitylates ULK1 for degradation by the proteasome. However, whereas ULK1 protein is degraded, ULK1 mRNA is actively transcribed. Upon reactivation of mTOR-dependent protein synthesis, basal levels of ULK1 are promptly restored, but the activity of newly synthesized ULK1 is inhibited by mTOR. This prepares the cell for a new possible round of autophagy stimulation. Our results thus place NEDD4L and ULK1 in a key position to control oscillatory activation of autophagy during prolonged stress to keep the levels of this process under a safe and physiological threshold. PMID:27932573

Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription FactorsD⃞

PubMed Central

Liu, Fang; Pore, Nabendu; Kim, Mijin; Voong, K. Ranh; Dowling, Melissa; Maity, Amit; Kao, Gary D.

2006-01-01

Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4. PMID:16280357

Effect of sound intensity on tonotopic fMRI maps in the unanesthetized monkey.

PubMed

Tanji, Kazuyo; Leopold, David A; Ye, Frank Q; Zhu, Charles; Malloy, Megan; Saunders, Richard C; Mishkin, Mortimer

2010-01-01

The monkey's auditory cortex includes a core region on the supratemporal plane (STP) made up of the tonotopically organized areas A1, R, and RT, together with a surrounding belt and a lateral parabelt region. The functional studies that yielded the tonotopic maps and corroborated the anatomical division into core, belt, and parabelt typically used low-amplitude pure tones that were often restricted to threshold-level intensities. Here we used functional magnetic resonance imaging in awake rhesus monkeys to determine whether, and if so how, the tonotopic maps and the pattern of activation in core, belt, and parabelt are affected by systematic changes in sound intensity. Blood oxygenation level-dependent (BOLD) responses to groups of low- and high-frequency pure tones 3-4 octaves apart were measured at multiple sound intensity levels. The results revealed tonotopic maps in the auditory core that reversed at the putative areal boundaries between A1 and R and between R and RT. Although these reversals of the tonotopic representations were present at all intensity levels, the lateral spread of activation depended on sound amplitude, with increasing recruitment of the adjacent belt areas as the intensities increased. Tonotopic organization along the STP was also evident in frequency-specific deactivation (i.e. "negative BOLD"), an effect that was intensity-specific as well. Regions of positive and negative BOLD were spatially interleaved, possibly reflecting lateral inhibition of high-frequency areas during activation of adjacent low-frequency areas, and vice versa. These results, which demonstrate the strong influence of tonal amplitude on activation levels, identify sound intensity as an important adjunct parameter for mapping the functional architecture of auditory cortex.

Neural bases of a specific strategy for visuospatial processing in rugby players.

PubMed

Sekiguchi, Atsushi; Yokoyama, Satoru; Kasahara, Satoshi; Yomogida, Yukihito; Takeuchi, Hikaru; Ogawa, Takeshi; Taki, Yasuyuki; Niwa, Shin-Ichi; Kawashima, Ryuta

2011-10-01

Rugby is one of the most tactically complex sports. Rugby coaching theory suggests that rugby players need to possess various cognitive abilities. A previous study claimed that rugby players have high visuospatial awareness, which is induced by a strategy described as taking a "bird's eye view." To examine if there were differential cortical networks related to visuospatial processing tasks among top-level rugby players and control novices, we compared brain activities during a visuospatial processing task between 20 male top-level rugby players (Top) and 20 control novice males (Novice) using functional magnetic resonance imaging (fMRI). To avoid the effect of differential behavioral performances on brain activation, we recruited novices whose visuospatial ability was expected to match that of the rugby players. We adopted a 3-D mental rotation task during fMRI scanning as a visuospatial processing task. Significantly greater activations from baseline were observed for the Top group than for the Novice group in the right superior parietal lobe and lateral occipital cortex. Significantly greater deactivations from baseline were observed for the Top group than for the Novice group in the right medial prefrontal cortex. The discrepancy between psychobehavioral outputs and the fMRI results suggested the existence of a cognitive strategy among top-level rugby players that differs from that among control novices. The greater activation of the right superior parietal lobe and lateral occipital cortex in top-level rugby players suggested a strategy involving visuospatial cognitive processing with respect to the bird's eye view. In addition, the right medial prefrontal cortex is known to be a part of the default mode networks, suggesting an additional cognitive load for the Top group when using the bird's-eye-view strategy. This further supported the existence of a specific cognitive strategy among top-level rugby players.

Differential conserted activity induced regulation of Nogo receptors (1-3), LOTUS and Nogo mRNA in mouse brain.

PubMed

Karlsson, Tobias E; Koczy, Josefin; Brené, Stefan; Olson, Lars; Josephson, Anna

2013-01-01

Nogo Receptor 1 (NgR1) mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity.

Differential Conserted Activity Induced Regulation of Nogo Receptors (1–3), LOTUS and Nogo mRNA in Mouse Brain

PubMed Central

Karlsson, Tobias E.; Koczy, Josefin; Brené, Stefan; Olson, Lars; Josephson, Anna

2013-01-01

Nogo Receptor 1 (NgR1) mRNA is downregulated in hippocampal and cortical regions by increased neuronal activity such as a kainic acid challenge or by exposing rats to running wheels. Plastic changes in cerebral cortex in response to loss of specific sensory inputs caused by spinal cord injury are also associated with downregulation of NgR1 mRNA. Here we investigate the possible regulation by neuronal activity of the homologous receptors NgR2 and NgR3 as well as the endogenous NgR1 antagonist LOTUS and the ligand Nogo. The investigated genes respond to kainic acid by gene-specific, concerted alterations of transcript levels, suggesting a role in the regulation of synaptic plasticity, Downregulation of NgR1, coupled to upregulation of the NgR1 antagonist LOTUS, paired with upregulation of NgR2 and 3 in the dentate gyrus suggest a temporary decrease of Nogo/OMgp sensitivity while CSPG and MAG sensitivity could remain. It is suggested that these activity-synchronized temporary alterations may serve to allow structural alterations at the level of local synaptic circuitry in gray matter, while maintaining white matter pathways and that subsequent upregulation of Nogo-A and NgR1 transcript levels signals the end of such a temporarily opened window of plasticity. PMID:23593344

Effects of Engineering Design-Based Science on Elementary School Science Students' Engineering Identity Development across Gender and Grade

NASA Astrophysics Data System (ADS)

Capobianco, Brenda M.; Yu, Ji H.; French, Brian F.

2015-04-01

The integration of engineering concepts and practices into elementary science education has become an emerging concern for science educators and practitioners, alike. Moreover, how children, specifically preadolescents (grades 1-5), engage in engineering design-based learning activities may help science educators and researchers learn more about children's earliest identification with engineering. The purpose of this study was to examine the extent to which engineering identity differed among preadolescents across gender and grade, when exposing students to engineering design-based science learning activities. Five hundred fifty preadolescent participants completed the Engineering Identity Development Scale (EIDS), a recently developed measure with validity evidence that characterizes children's conceptions of engineering and potential career aspirations. Data analyses of variance among four factors (i.e., gender, grade, and group) indicated that elementary school students who engaged in the engineering design-based science learning activities demonstrated greater improvements on the EIDS subscales compared to those in the comparison group. Specifically, students in the lower grade levels showed substantial increases, while students in the higher grade levels showed decreases. Girls, regardless of grade level and participation in the engineering learning activities, showed higher scores in the academic subscale compared to boys. These findings suggest that the integration of engineering practices in the science classroom as early as grade one shows potential in fostering and sustaining student interest, participation, and self-concept in engineering and science.

Meeting Report: Batch-to-Batch Variability in Estrogenic Activity in Commercial Animal Diets—Importance and Approaches for Laboratory Animal Research

PubMed Central

Heindel, Jerrold J.; vom Saal, Frederick S.

2008-01-01

We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research. PMID:18335108

Chemical release from single-PMMA microparticles monitored by CARS microscopy

NASA Astrophysics Data System (ADS)

Enejder, Annika; Svedberg, Fredrik; Nordstierna, Lars; Nydén, Magnus

2011-03-01

Microparticles loaded with antigens, proteins, DNA, fungicides, and other functional agents emerge as ideal vehicles for vaccine, drug delivery, genetic therapy, surface- and crop protection. The microscopic size of the particles and their collective large specific surface area enables highly active and localized release of the functional substance. In order to develop designs with release profiles optimized for the specific application, it is desirable to map the distribution of the active substance within the particle and how parameters such as size, material and morphology affect release rates at single particle level. Current imaging techniques are limited in resolution, sensitivity, image acquisition time, or sample treatment, excluding dynamic studies of active agents in microparticles. Here, we demonstrate that the combination of CARS and THG microscopy can successfully be used, by mapping the spatial distribution and release rates of the fungicide and food preservative IPBC from different designs of PMMA microparticles at single-particle level. By fitting a radial diffusion model to the experimental data, single particle diffusion coefficients can be determined. We show that release rates are highly dependent on the size and morphology of the particles. Hence, CARS and THG microscopy provides adequate sensitivity and spatial resolution for quantitative studies on how singleparticle properties affect the diffusion of active agents at microscopic level. This will aid the design of innovative microencapsulating systems for controlled release.

Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets--importance and approaches for laboratory animal research.

PubMed

Heindel, Jerrold J; vom Saal, Frederick S

2008-03-01

We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research.

Language-invariant verb processing regions in Spanish-English bilinguals.

PubMed

Willms, Joanna L; Shapiro, Kevin A; Peelen, Marius V; Pajtas, Petra E; Costa, Albert; Moo, Lauren R; Caramazza, Alfonso

2011-07-01

Nouns and verbs are fundamental grammatical building blocks of all languages. Studies of brain-damaged patients and healthy individuals have demonstrated that verb processing can be dissociated from noun processing at a neuroanatomical level. In cases where bilingual patients have a noun or verb deficit, the deficit has been observed in both languages. This suggests that the noun-verb distinction may be based on neural components that are common across languages. Here we investigated the cortical organization of grammatical categories in healthy, early Spanish-English bilinguals using functional magnetic resonance imaging (fMRI) in a morphophonological alternation task. Four regions showed greater activity for verbs than for nouns in both languages: left posterior middle temporal gyrus (LMTG), left middle frontal gyrus (LMFG), pre-supplementary motor area (pre-SMA), and right middle occipital gyrus (RMOG); no regions showed greater activation for nouns. Multi-voxel pattern analysis within verb-specific regions showed indistinguishable activity patterns for English and Spanish, indicating language-invariant bilingual processing. In LMTG and LMFG, patterns were more similar within than across grammatical category, both within and across languages, indicating language-invariant grammatical class information. These results suggest that the neural substrates underlying verb-specific processing are largely independent of language in bilinguals, both at the macroscopic neuroanatomical level and at the level of voxel activity patterns. Copyright © 2011 Elsevier Inc. All rights reserved.

Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients.

PubMed

Abd Al Samid, May; Chaudhary, Belal; Khaled, Yazan S; Ammori, Basil J; Elkord, Eyad

2016-03-22

Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3-Helios+ and activated FoxP3+/-Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3-LAP+ Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+ activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP-/+LAP+ CD4+ T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.

Ion sensing method

DOEpatents

Smith, Richard Harding; Martin, Glenn Brian

2004-05-18

The present invention allows the determination of trace levels of ionic substances in a sample solution (ions, metal ions, and other electrically charged molecules) by coupling a separation method, such as liquid chromatography, with ion selective electrodes (ISE) prepared so as to allow detection at activities below 10.sup.-6 M. The separation method distributes constituent molecules into fractions due to unique chemical and physical properties, such as charge, hydrophobicity, specific binding interactions, or movement in an electrical field. The separated fractions are detected by means of the ISE(s). These ISEs can be used singly or in an array. Accordingly, modifications in the ISEs are used to permit detection of low activities, specifically, below 10.sup.-6 M, by using low activities of the primary analyte (the molecular species which is specifically detected) in the inner filling solution of the ISE. Arrays constructed in various ways allow flow-through sensing for multiple ions.

The influence of biotic and abiotic factors on (137)Cs accumulation in higher fungi after the accident at Chernobyl NPP.

PubMed

Zarubina, N

2016-09-01

Levels of soil contamination with (137)Cs, the belonging of fungi to a certain ecological group, the localization depth of the main part of mycelium in soil are the primary factors influencing the value of (137)Cs specific activity in higher fungi after the accident at Chernobyl NPP. It has been found that the value of (137)Cs specific activity in fungi of one species could vary by more than 10 times during a vegetation period. A correlation between the changes of (137)Cs content in fungi during the vegetation period and the amount of precipitates during various periods preceding the collection of samples has not been determined. An assumption has been proposed stating dependence between peculiarities of mycelium growth during the vegetation period and the changes of (137)Cs specific activity in fungi. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

PubMed

Rudolfsson, Thomas; Björklund, Martin; Svedmark, Åsa; Srinivasan, Divya; Djupsjöbacka, Mats

2017-01-01

Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

NASA Technical Reports Server (NTRS)

Zhang, Xiang (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Ellman, Jonathan A. (Inventor); Sun, Cheng (Inventor)

2014-01-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

DOEpatents

Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

2014-04-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

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.

Biochemical and Genetic Evidence for the Presence of Multiple Phosphatidylinositol- and Phosphatidylinositol 4,5-Bisphosphate-Specific Phospholipases C in Tetrahymena▿‡

PubMed Central

Leondaritis, George; Sarri, Theoni; Dafnis, Ioannis; Efstathiou, Antonia; Galanopoulou, Dia

2011-01-01

Eukaryotic phosphoinositide-specific phospholipases C (PI-PLC) specifically hydrolyze phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], produce the Ca2+-mobilizing agent inositol 1,4,5-trisphosphate, and regulate signaling in multicellular organisms. Bacterial PtdIns-specific PLCs, also present in trypanosomes, hydrolyze PtdIns and glycosyl-PtdIns, and they are considered important virulence factors. All unicellular eukaryotes studied so far contain a single PI-PLC-like gene. In this report, we show that ciliates are an exception, since we provide evidence that Tetrahymena species contain two sets of functional genes coding for both bacterial and eukaryotic PLCs. Biochemical characterization revealed two PLC activities that differ in their phosphoinositide substrate utilization, subcellular localization, secretion to extracellular space, and sensitivity to Ca2+. One of these activities was identified as a typical membrane-associated PI-PLC activated by low-micromolar Ca2+, modestly activated by GTPγS in vitro, and inhibited by the compound U73122 [1-(6-{[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione]. Importantly, inhibition of PI-PLC in vivo resulted in rapid upregulation of PtdIns(4,5)P2 levels, suggesting its functional importance in regulating phosphoinositide turnover in Tetrahymena. By in silico and molecular analysis, we identified two PLC genes that exhibit significant similarity to bacterial but not trypanosomal PLC genes and three eukaryotic PI-PLC genes, one of which is a novel inactive PLC similar to proteins identified only in metazoa. Comparative studies of expression patterns and PI-PLC activities in three T. thermophila strains showed a correlation between expression levels and activity, suggesting that the three eukaryotic PI-PLC genes are functionally nonredundant. Our findings imply the presence of a conserved and elaborate PI-PLC-Ins(1,4,5)P3-Ca2+ regulatory axis in ciliates. PMID:21169416

Laminar- and Target-Specific Amygdalar Inputs in Rat Primary Gustatory Cortex.

PubMed

Haley, Melissa S; Fontanini, Alfredo; Maffei, Arianna

2016-03-02

The primary gustatory cortex (GC) receives projections from the basolateral nucleus of the amygdala (BLA). Behavioral and electrophysiological studies demonstrated that this projection is involved in encoding the hedonic value of taste and is a source of anticipatory activity in GC. Anatomically, this projection is largest in the agranular portion of GC; however, its synaptic targets and synaptic properties are currently unknown. In vivo electrophysiological recordings report conflicting evidence about BLA afferents either selectively activating excitatory neurons or driving a compound response consistent with the activation of inhibitory circuits. Here we demonstrate that BLA afferents directly activate excitatory neurons and two distinct populations of inhibitory neurons in both superficial and deep layers of rat GC. BLA afferents recruit different proportions of excitatory and inhibitory neurons and show distinct patterns of circuit activation in the superficial and deep layers of GC. These results provide the first circuit-level analysis of BLA inputs to a sensory area. Laminar- and target-specific differences of BLA inputs likely explain the complexity of amygdalocortical interactions during sensory processing. Projections from the basolateral nucleus of the amygdala (BLA) to the cortex convey information about the emotional value and the expectation of a sensory stimulus. Although much work has been done to establish the behavioral role of BLA inputs to sensory cortices, very little is known about the circuit organization of BLA projections. Here we provide the first in-depth analysis of connectivity and synaptic properties of the BLA input to the gustatory cortex. We show that BLA afferents activate excitatory and inhibitory circuits in a layer-specific and pattern-specific manner. Our results provide important new information about how neural circuits establishing the hedonic value of sensory stimuli and driving anticipatory behaviors are organized at the synaptic level. Copyright © 2016 the authors 0270-6474/16/362623-15$15.00/0.

Patterning of somatosympathetic reflexes

NASA Technical Reports Server (NTRS)

Kerman, I. A.; Yates, B. J.

1999-01-01

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (approximately 60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (approximately 20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.

90Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident

NASA Astrophysics Data System (ADS)

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

2016-04-01

Here we determined the 90Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. 90Sr activity concentrations in the teeth varied from 6-831 mBq (g Ca)-1 and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of 90Sr (Bq (g Sr)-1) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high 90Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that 90Sr is incorporated into the teeth during tooth development; thus, tooth 90Sr activity concentrations reflect environmental 90Sr levels during tooth formation. Assessment of 90Sr in teeth could provide useful information about internal exposure to 90Sr radiation and allow for the measurement of time-course changes in the degree of environmental 90Sr pollution.

(90)Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident.

PubMed

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

2016-04-05

Here we determined the (90)Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. (90)Sr activity concentrations in the teeth varied from 6-831 mBq (g Ca)(-1) and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of (90)Sr (Bq (g Sr)(-1)) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high (90)Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that (90)Sr is incorporated into the teeth during tooth development; thus, tooth (90)Sr activity concentrations reflect environmental (90)Sr levels during tooth formation. Assessment of (90)Sr in teeth could provide useful information about internal exposure to (90)Sr radiation and allow for the measurement of time-course changes in the degree of environmental (90)Sr pollution.

90Sr in teeth of cattle abandoned in evacuation zone: Record of pollution from the Fukushima-Daiichi Nuclear Power Plant accident

PubMed Central

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

2016-01-01

Here we determined the 90Sr concentrations in the teeth of cattle abandoned in the evacuation area of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident. 90Sr activity concentrations in the teeth varied from 6–831 mBq (g Ca)−1 and exhibited a positive relationship with the degree of radioactive contamination that the cattle experienced. Even within an individual animal, the specific activity of 90Sr (Bq (g Sr)−1) varied depending on the development stage of the teeth during the FNPP accident: teeth that were early in development exhibited high 90Sr specific activities, while teeth that were late in development exhibited low specific activities. These findings demonstrate that 90Sr is incorporated into the teeth during tooth development; thus, tooth 90Sr activity concentrations reflect environmental 90Sr levels during tooth formation. Assessment of 90Sr in teeth could provide useful information about internal exposure to 90Sr radiation and allow for the measurement of time-course changes in the degree of environmental 90Sr pollution. PMID:27045764

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

THE LOCALIZATION OF CHOLINESTERASE ACTIVITY IN RAT CARDIAC MUSCLE BY ELECTRON MICROSCOPY

PubMed Central

Karnovsky, Morris J.

1964-01-01

A method has been developed for localizing sites of cholinesterase activity in rat cardiac muscle by electron microscopy. The method utilizes thiocholine esters as substrates, and is believed to be dependent on the reduction of ferricyanide to ferrocyanide by thiocholine released by enzymatic activity. The ferrocyanide thus formed is captured by copper to form fine, electron-opaque deposits of copper ferrocyanide, which sharply delineate sites of enzymatic activity at the ultrastructural level. Cholinesterase activity in formalin-fixed heart muscle was localized: (a) in longitudinal elements of the sarcoplasmic reticulum, but not in the T, or transverse, elements; and (b) in the A band, with virtually no activity noted in the M band, or in the H zone. The I band was also negative. No activity was detected in the sarcolemma, or in invaginations of the sarcolemma at the level of the Z band. The perinuclear element of the sarcoplasmic (endoplasmic) reticulum was frequently strongly positive. Activity at all sites was completely abolished by omitting the substrates, or by inhibition with eserine 10-4 M and diisopropylfluorophosphate 10-5 M. Eserine 10-5 M completely inhibited reaction in the sarcoplasmic reticulum, and virtually abolished that in the A band. These observations, together with the use of the relatively specific substrates and suitable controls to eliminate non-enzymatic staining, indicate that cholinesterase activity was being demonstrated. The activity in rat heart against different substrates was that of non-specific cholinesterases, in accordance with biochemical data. The activity in the A band was considered to be probably due to myosincholinesterase. It is proposed that the localization of cholinesterases in myocardium at the ultrastructural level should be taken into account in considering the possible functions of these myocardial enzymes, and it is hoped that knowledge of their localization will open up new avenues of approach in considering their physiological role in myocardium, which at present is not definitely known. PMID:14222810

Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review

PubMed Central

Friedenreich, Christine M.; Courneya, Kerry S.; Siddiqi, Sameer M.; McTiernan, Anne; Alfano, Catherine M.

2012-01-01

Background Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers. Methods We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity). Results There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer–specific, and colon cancer–specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary. Conclusions Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized controlled trials of exercise with biomarker and cancer-specific disease endpoints, such as recurrence, new primary cancers, and cancer-specific mortality in cancer survivors, are warranted. PMID:22570317

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis

PubMed Central

Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

2016-01-01

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway. PMID:27572318

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis.

PubMed

Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

2016-09-27

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.

Identification of the active protein in rice bran protein having an inhibitory activity of cholesterol micellar solubility.

PubMed

Wang, Jilite; Shimada, Masaya; Nagaoka, Satoshi

2017-06-01

In our previous study, rice bran protein (RBP) inhibited cholesterol micellar solubility in vitro and decreased serum cholesterol level in rats. In the present study, RBP was separated and purified by size-exclusion chromatography and reversed-phase chromatography. The active protein of RBP related to cholesterol micellar solubility was identified as lectin and non-specific lipid-transfer protein 1 using MALDI-TOF mass spectrometry analysis.

Into the Curriculum. Reading/Language Arts: Arabian Nights; Reading/Language Arts: Birds in Picture Books: Characters, Plots, and Themes; Science: Birds in Their Nests; Social Studies: Written with Quills; Social Studies: Baghdad and Iraq History.

ERIC Educational Resources Information Center

School Library Media Activities Monthly, 2003

2003-01-01

Provides five fully developed library media activities that are designed for use with specific curriculum units in reading, language arts, science, and social studies. Library media skills, curriculum objectives, grade levels, resources, instructional roles, activities and procedures, evaluation, and follow-up are described for each activity. (LRW)

Relationship between physical activity and disability in low back pain: a systematic review and meta-analysis.

PubMed

Lin, Chung-Wei Christine; McAuley, James H; Macedo, Luciana; Barnett, Dominique C; Smeets, Rob J; Verbunt, Jeanine A

2011-03-01

It is often assumed that patients with pain-related disability due to low back pain (LBP) will have reduced physical activity levels, but recent studies have provided results that challenge this assumption. The aim of our systematic review was to examine the relationship between physical activity and disability in LBP. The literature search included 6 electronic databases and the reference list of relevant systematic reviews and studies to May 2010. To be included, studies had to measure both disability (eg, with the Roland Morris Disability Questionnaire) and physical activity (eg, by accelerometry) in patients with non-specific LBP. Two independent reviewers screened search results and extracted data, and authors were contacted for additional data. Correlation coefficients were pooled using the random-effects model. The search identified 3213 records and 18 studies were eligible for inclusion. The pooled results showed a weak relationship between physical activity and disability in acute or subacute (<3months) LBP (r=-0.08, 95% confidence interval=-0.17 to 0.002), and a moderate and negative relationship in chronic (>3months) LBP (r=-0.33, 95% confidence interval=-0.51 to -0.15). That is, persons with acute or subacute LBP appear to vary in the levels of physical activity independent of their pain-related disability. Persons with chronic LBP with high levels of disability are also likely to have low levels of physical activity. Persons with acute or subacute back pain appear to vary in the levels of physical activity independent of disability. Persons with chronic back pain with high levels of disability will likely have low levels of physical activity. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Use of a consumer market activity monitoring and feedback device improves exercise capacity and activity levels in COPD.

PubMed

Caulfield, Brian; Kaljo, Indira; Donnelly, Seamas

2014-01-01

COPD is associated with a gradual decline in physical activity, which itself contributes to a worsening of the underlying condition. Strategies that improve physical activity levels are critical to halt this cycle. Wearable sensor based activity monitoring and persuasive feedback might offer a potential solution. However it is not clear just how much intervention might be needed in this regard - i.e. whether programmes need to be tailored specifically for the target clinical population or whether more simple activity monitoring and feedback solutions, such as that offered in consumer market devices, might be sufficient. This research was carried out to investigate the impact of 4 weeks of using an off the shelf consumer market activity monitoring and feedback application on measures of physical activity, exercise capacity, and health related quality of life in a population of 10 Stage I and II COPD patients. Results demonstrate a significant and positive effect on exercise capacity (measured using a 6-minute walk test) and activity levels (measured in terms of average number of steps per hour) yet no impact on health related quality of life (St Georges Respiratory Disease Questionnaire).

Association of dietary pattern and physical activity level with triglyceride to high-density lipoprotein cholesterol ratio among adults in Jiangsu, China: a cross-sectional study with sex-specific differences.

PubMed

Lyu, Shurong; Su, Jian; Xiang, Quanyong; Wu, Ming

2014-08-01

Our study aims to explore the association between dietary patterns and physical activity levels (PAL) with a triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and to examine whether the association is sex dependent among Chinese adults. In this cross-sectional study, data were collected through questionnaires, anthropometric measurement, and biochemical tests. Four food patterns ("meat," "healthy," "high-energy," and "traditional Chinese") were established through factor analysis. Physical activity level was categorized as "active," "moderate," and "inactive." Logistic regression models were used to determine the associations between food patterns and PAL with TG/HDL-C ratio. Compared with quartile 1, quartiles 2 and 3 of meat pattern among men were found to be associated with lower risk of high TG/HDL-C ratio (the highest quartile of TG/HDL-C ratio). Similar decreased risk of high TG/HDL-C ratio was also observed in the highest quartile 4 of healthy pattern among women. Active PAL was protective against high TG/HDL-C ratio among both men (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.55-0.86) and women (OR, 0.77; 95% CI, 0.62-0.96). Although no statistically significant interaction was observed, we found that individuals with active PAL and low healthy diet had a similar OR with those with inactive PAL and high healthy diet (0.62 vs 0.68). In conclusion, dietary patterns were associated with TG/HDL-C ratio in a sex-specific way, and active PAL was consistently related to decreased risk of high TG/HDL-C ratio across genders. Copyright © 2014 Elsevier Inc. All rights reserved.

The murine SP-C promoter directs type II cell-specific expression in transgenic mice.

PubMed

Glasser, Stephan W; Eszterhas, Susan K; Detmer, Emily A; Maxfield, Melissa D; Korfhagen, Thomas R

2005-04-01

Genomic DNA from the mouse pulmonary surfactant protein C (SP-C) gene was analyzed in transgenic mice to identify DNA essential for alveolar type II cell-specific expression. SP-C promoter constructs extending either 13 or 4.8 kb upstream of the transcription start site directed lung-specific expression of the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. In situ hybridization analysis demonstrated alveolar cell-specific expression in the lungs of adult transgenic mice, and the pattern of 4.8 SP-C-CAT expression during development paralleled that of the endogenous SP-C gene. With the use of deletion constructs, lung-specific, low-level CAT activity was detected in tissue assays of SP-C-CAT transgenic mice retaining 318 bp of the promoter. In transient and stable cell transfection experiments, the 4.8-kb SP-C promoter was 90-fold more active as a stably integrated gene. These findings indicate that 1) the 4.8-kb SP-C promoter is sufficient to direct cell-specific and developmental expression, 2) an enhancer essential for lung-specific expression maps to the proximal 318-bp promoter, and 3) the activity of the 4.8-kb SP-C promoter construct is highly dependent on its chromatin environment.

Serum Gelatinases Levels in Multiple Sclerosis Patients during 21 Months of Natalizumab Therapy

PubMed Central

Bellini, Tiziana; Trentini, Alessandro; Delbue, Serena; Elia, Francesca; Gastaldi, Matteo; Franciotta, Diego; Bergamaschi, Roberto; Manfrinato, Maria Cristina; Volta, Carlo Alberto; Granieri, Enrico; Fainardi, Enrico

2016-01-01

Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab. PMID:27340316

An EDMD mutation in C. elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity.

PubMed

Mattout, Anna; Pike, Brietta L; Towbin, Benjamin D; Bank, Erin M; Gonzalez-Sandoval, Adriana; Stadler, Michael B; Meister, Peter; Gruenbaum, Yosef; Gasser, Susan M

2011-10-11

In worms, as in other organisms, many tissue-specific promoters are sequestered at the nuclear periphery when repressed and shift inward when activated. It has remained unresolved, however, whether the association of facultative heterochromatin with the nuclear periphery, or its release, has functional relevance for cell or tissue integrity. Using ablation of the unique lamin gene in C. elegans, we show that lamin is necessary for the perinuclear positioning of heterochromatin. We then express at low levels in otherwise wild-type worms a lamin carrying a point mutation, Y59C, which in humans is linked to an autosomal-dominant form of Emery-Dreifuss muscular dystrophy. Using embryos and differentiated tissues, we track the subnuclear position of integrated heterochromatic arrays and their expression. In LMN-1 Y59C-expressing worms, we see abnormal retention at the nuclear envelope of a gene array bearing a muscle-specific promoter. This correlates with impaired activation of the array-borne myo-3 promoter and altered expression of a number of muscle-specific genes. However, an equivalent array carrying the intestine-specific pha-4 promoter is expressed normally and shifts inward when activated in gut cells of LMN-1 Y59C worms. Remarkably, adult LMN-1 Y59C animals have selectively perturbed body muscle ultrastructure and reduced muscle function. Lamin helps sequester heterochromatin at the nuclear envelope, and wild-type lamin permits promoter release following tissue-specific activation. A disease-linked point mutation in lamin impairs muscle-specific reorganization of a heterochromatic array during tissue-specific promoter activation in a dominant manner. This dominance and the correlated muscle dysfunction in LMN-1 Y59C worms phenocopies Emery-Dreifuss muscular dystrophy. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-04-26

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

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

PubMed Central

Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)

PubMed Central

Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya

2013-01-01

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression. PMID:23807510

Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT).

PubMed

Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya

2013-06-27

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression.

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

PubMed Central

Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Cartwright, Keith; Miller, Elizabeth

2001-01-01

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy. PMID:11254596

Somatic, but not cognitive, symptoms of anxiety predict lower levels of physical activity in panic disorder patients.

PubMed

Belem da Silva, Cristiano Tschiedel; Schuch, Felipe; Costa, Marianna; Hirakata, Vania; Manfro, Gisele Gus

2014-08-01

Anxiety disorders have gathered much attention as possible risk factors for the development of cardiovascular disease (CVD), possibly mediated by an unhealthy lifestyle (e.g. low physical activity). However, prospective studies on anxiety disorders and CVD show conflicting results. A possible explanation is that somatic symptoms of anxiety may have a more specific cardiovascular effect than cognitive symptoms across different anxiety disorders. The present study investigated the association between cognitive and somatic symptoms of anxiety and physical activity (PA) in a sample of panic disorder (PD) outpatients. One-hundred and two outpatients with a lifetime diagnosis of PD from a previously studied cohort were contacted. Patients were evaluated throughout the MINI, the Beck Anxiety Inventory (BAI) and the International Physical Activity Questionnaire (IPAQ). After performing a multivariate regression analysis, groups were divided into high and low somatic anxiety. Patients with high somatic anxiety showed a significantly higher prevalence of low level of PA as compared to those with low somatic anxiety (62.5 versus 34.3%; χ²= 5.33; df=1; P=.021). Somatic symptoms of anxiety remained the only important predictors of low level of PA (odds ratio [OR] 2.81; 95% CI 1.00-7.90; p=.050) in the multivariate model. The main limitations of the present study are the cross-sectional design and the small sample size. Results support specific effects of somatic symptoms of anxiety on risk for low level of PA, which might explain inconsistent results regarding CVD risk in the literature. Copyright © 2014 Elsevier B.V. All rights reserved.

Saliva secretory IgA antibodies against molds and mycotoxins in patients exposed to toxigenic fungi.

PubMed

Vojdani, Aristo; Kashanian, Albert; Vojdani, Elroy; Campbell, Andrew W

2003-11-01

Upper respiratory exposure to different environmental antigens results first in the activation of mucosal immunity and production of IgA antibodies in different secretions including saliva. Despite this there is no study, which addresses secretory antibodies against molds and mycotoxins. The purpose of this study was to evaluate mold-specific salivary IgA in individuals exposed to molds and mycotoxins in a water-damaged building environment. Saliva IgA antibody levels against seven different molds and two mycotoxins were studied in 40 patients exposed to molds and in 40 control subjects. Mold-exposed patients showed significantly higher levels of salivary IgA antibodies against one or more mold species. A majority of patients with high IgA antibodies against molds exhibited elevation in salivary IgA against mycotoxins, as well. These IgA antibodies against molds and mycotoxins are specific, since using molds and mycotoxins in immune absorption could reduce antibody levels, significantly. Detection of high counts of molds in water-damaged buildings, strongly suggests the existence of a reservoir of mold spores in the environment. This viable microbial activity with specific mold and mycotoxin IgA in saliva may assist in the diagnosis of mold exposure. Whether mold and mycotoxin specific IgA antibodies detected in saliva are indicative of the role of IgA antibodies in the late phase of type-1 hypersensitivity reaction or in type-2 and type-3 delayed sensitivities is a matter that warrants further investigation.

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

Toward Increasing Professionalism in Public Relations: An Activity-Specific System for Categorizing Practitioners.

ERIC Educational Resources Information Center

Brownell, Mark A.; Niebauer, Walter E., Jr.

To develop a method of categorizing public relations practitioners according to a hierarchy of professionalism which would also identify what training is needed to raise those in lower levels to higher levels, a study surveyed 93 Iowa practitioners listed in the 1986-87 Public Relations Society of America Register Issue. Response rate was 66% and…

Humoral immune responses of experimentally Eimeria ninakholyakimovae-infected goat kids.

PubMed

Matos, Lorena; Muñoz, María Del Carmen; Molina, José Manuel; Ferrer, Otilia; Rodríguez, Francisco; Pérez, Davinia; López, Adassa María; Martín, Sergio; Hermosilla, Carlos; Taubert, Anja; Ruiz, Antonio

2017-04-01

Although cellular immune reactions seem to be crucial for protective immune responses in Eimeria spp. infections, there are also evidences on an active involvement of the humoral counterpart. In the present study, we have analyzed the humoral response of goat kids subjected to primary and challenge infections with Eimeria ninakholyakimovae. Specific levels of IgG and IgM in serum samples and IgA in the ileal mucus were estimated. In infected kids, significantly increased levels of IgG were observed from 3 weeks post infection onwards in addition to an enhancement of specific IgM and secretory IgA levels. A wide range of peptides of sporulated oocyst antigen (SOA) was recognized by specific IgG as determined by immunoblotting. However, no correlations were found between immunoglobulin levels and OPG counts after challenge infection. Overall, these data indicate a significant specific humoral response of E. ninakohlyakimovae-infected goat kids that does not seem to convey immunoprotection. Further studies should be addressed to clarify if the lack of correlation might be associated to the type of antigen used for the immunoenzimatic assays, the age of the animals or other factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Involvement of specific calmodulin isoforms in salicylic acid-independent activation of plant disease resistance responses.

PubMed

Heo, W D; Lee, S H; Kim, M C; Kim, J C; Chung, W S; Chun, H J; Lee, K J; Park, C Y; Park, H C; Choi, J Y; Cho, M J

1999-01-19

The Ca2+ signal is essential for the activation of plant defense responses, but downstream components of the signaling pathway are still poorly defined. Here we demonstrate that specific calmodulin (CaM) isoforms are activated by infection or pathogen-derived elicitors and participate in Ca2+-mediated induction of plant disease resistance responses. Soybean CaM (SCaM)-4 and SCaM-5 genes, which encode for divergent CaM isoforms, were induced within 30 min by a fungal elicitor or pathogen, whereas other SCaM genes encoding highly conserved CaM isoforms did not show such response. This pathogen-triggered induction of these genes specifically depended on the increase of intracellular Ca2+ level. Constitutive expression of SCaM-4 and SCaM-5 in transgenic tobacco plants triggered spontaneous induction of lesions and induces an array of systemic acquired resistance (SAR)-associated genes. Surprisingly, these transgenic plants have normal levels of endogenous salicylic acid (SA). Furthermore, coexpression of nahG gene did not block the induction of SAR-associated genes in these transgenic plants, indicating that SA is not involved in the SAR gene induction mediated by SCaM-4 or SCaM-5. The transgenic plants exhibit enhanced resistance to a wide spectrum of virulent and avirulent pathogens, including bacteria, fungi, and virus. These results suggest that specific CaM isoforms are components of a SA-independent signal transduction chain leading to disease resistance.

Mythology.

ERIC Educational Resources Information Center

Web Feet K-8, 2001

2001-01-01

This annotated subject guide to Web sites and additional resources focuses on mythology. Specific age levels are given for resources that include Web sites, CD-ROMs and software, videos, books, audios, and magazines; offers professional resources; and presents a relevant class activity. (LRW)

Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.

PubMed

Ha, Byung Hak; Morse, Elizabeth M; Turk, Benjamin E; Boggon, Titus J

2015-05-22

The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantifying substrate uptake by individual cells of marine bacterioplankton by catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography.

PubMed

Sintes, Eva; Herndl, Gerhard J

2006-11-01

Catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography (MICRO-CARD-FISH) is increasingly being used to obtain qualitative information on substrate uptake by individual members of specific prokaryotic communities. Here we evaluated the potential for using this approach quantitatively by relating the measured silver grain area around cells taking up (3)H-labeled leucine to bulk leucine uptake measurements. The increase in the silver grain area over time around leucine-assimilating cells of coastal bacterial assemblages was linear during 4 to 6 h of incubation. By establishing standardized conditions for specific activity levels and concomitantly performing uptake measurements with the bulk community, MICRO-CARD-FISH can be used quantitatively to determine uptake rates on a single-cell level. Therefore, this approach allows comparisons of single-cell activities for bacterial communities obtained from different sites or growing under different ecological conditions.

Quantifying Substrate Uptake by Individual Cells of Marine Bacterioplankton by Catalyzed Reporter Deposition Fluorescence In Situ Hybridization Combined with Microautoradiography▿

PubMed Central

Sintes, Eva; Herndl, Gerhard J.

2006-01-01

Catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography (MICRO-CARD-FISH) is increasingly being used to obtain qualitative information on substrate uptake by individual members of specific prokaryotic communities. Here we evaluated the potential for using this approach quantitatively by relating the measured silver grain area around cells taking up 3H-labeled leucine to bulk leucine uptake measurements. The increase in the silver grain area over time around leucine-assimilating cells of coastal bacterial assemblages was linear during 4 to 6 h of incubation. By establishing standardized conditions for specific activity levels and concomitantly performing uptake measurements with the bulk community, MICRO-CARD-FISH can be used quantitatively to determine uptake rates on a single-cell level. Therefore, this approach allows comparisons of single-cell activities for bacterial communities obtained from different sites or growing under different ecological conditions. PMID:16950912

[Ecological and economic approaches to removing radioactively dangerous objects from service].

PubMed

Korenkov, I P; Lashchenova, T N; Neveĭkin, P P; Shandala, N K; Veselov, E I; Maksimova, O A

2011-01-01

The paper considers major ecological and economic problems when removing radiation dangerous objects from service and rehabilitating the areas, which require their solution: the absence of specific guidelines for ranking the contaminated lands exposed to radioactive and chemical pollution from the potential risk to the population and environment; no clear criteria for ceasing area rehabilitation works; radiation exposure levels for the population living in the areas after rehabilitation; allowable levels of residual specific activity, and levels of heavy metals in soil, surface and underground water and bed sediment. The cost such works is the most important and decisive problem. A decision-making algorithm consisting of three main blocks: organizational-technical, engineering, geological and medicoecological measures is proposed to solve managerial, economic, and scientific problems.

Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

PubMed

Medellin-Kowalewski, Alexandra; Wilkens, Rune; Wilson, Alexandra; Ruan, Ji; Wilson, Stephanie R

2016-01-01

The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%. Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.

Graphing Calculators, the CBL2[TM] and TI-Interactive[TM] in High School Science.

ERIC Educational Resources Information Center

Molnar, Bill

This collection of activities is designed to show how TI-Interactive[TM] and Calculator-based Laboratories (CBL) can be used to explore topics in high school science. The activities address such topics as specific heat, Boyle's Law, Newton's Law of Cooling, and Antarctic Ozone Levels. Teaching notes and calculator instructions are included as are…

Russian Language Testing and Integrated Examination for Foreign Citizens in Russia: Legislation Background and Legal Regulation Specific Features

ERIC Educational Resources Information Center

Dolzhikova, Anzhela

2015-01-01

The Russian Federation faces active law-making and legislative activities aimed at providing legal grounds for qualifying educational level of foreign nationals entering the country with the purpose to work and apply for citizenship. The article deals with the current legislation and regulations in their relationship with each other, their impact…