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  1. Comparing Trans-Spectrum and Same-Sex-Attracted Youth in Australia: Increased Risks, Increased Activisms

    ERIC Educational Resources Information Center

    Jones, Tiffany; Hillier, Lynne

    2013-01-01

    Tran-spectrum youth include those who are gender questioning, transgender, intersex, genderqueer, and androgynous. Drawing on data from an Australian study of more than 3,000 same-sex-attracted and trans-spectrum youth aged 14 to 21, this article compares a group of 91 trans-spectrum youth from the study to "cisgender" same-sex-attracted…

  2. Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to the Smad MH2 fold.

    PubMed

    Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta; Benach, Jordi; Riera, Antoni; Pous, Joan; Macias, Maria J

    2015-04-01

    Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.

  3. Start2Fold: a database of hydrogen/deuterium exchange data on protein folding and stability

    PubMed Central

    Pancsa, Rita; Varadi, Mihaly; Tompa, Peter; Vranken, Wim F.

    2016-01-01

    Proteins fulfil a wide range of tasks in cells; understanding how they fold into complex three-dimensional (3D) structures and how these structures remain stable while retaining sufficient dynamics for functionality is essential for the interpretation of overall protein behaviour. Since the 1950's, solvent exchange-based methods have been the most powerful experimental means to obtain information on the folding and stability of proteins. Considerable expertise and care were required to obtain the resulting datasets, which, despite their importance and intrinsic value, have never been collected, curated and classified. Start2Fold is an openly accessible database (http://start2fold.eu) of carefully curated hydrogen/deuterium exchange (HDX) data extracted from the literature that is open for new submissions from the community. The database entries contain (i) information on the proteins investigated and the underlying experimental procedures and (ii) the classification of the residues based on their exchange protection levels, also allowing for the instant visualization of the relevant residue groups on the 3D structures of the corresponding proteins. By providing a clear hierarchical framework for the easy sharing, comparison and (re-)interpretation of HDX data, Start2Fold intends to promote a better understanding of how the protein sequence encodes folding and structure as well as the development of new computational methods predicting protein folding and stability. PMID:26582925

  4. Medicare's Hospital Compare quality reports appear to have slowed price increases for two major procedures.

    PubMed

    Dor, Avi; Encinosa, William E; Carey, Kathleen

    2015-01-01

    Previous research has found that Hospital Compare, Medicare's public reporting initiative, has had little impact on patient outcomes. However, little is known about the initiative's impact on hospital prices, which may be significant because private insurers are generally well positioned to respond to quality information when negotiating prices with hospitals. We estimated difference-in-differences models of the effects of Hospital Compare quality reporting on transaction prices for two major cardiac procedures, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). States that had mandated their own public reporting systems before the implementation of Hospital Compare formed the control group. We found that prices for these procedures continued to increase overall after the initiation of Hospital Compare quality scores, but the rate of increase was significantly lower in states with no quality reporting metrics of their own before Hospital Compare, when compared to the control states (annual rates of increase of 4.4 percent versus 8.7 percent for PCI, and 3.9 percent versus 10.6 percent for CABG, adjusted for overall inflation). This finding implies that Hospital Compare provided leverage to purchasers in moderating price increases, while adding competitive pressures on hospitals. Providing accurate quality information on both hospitals and health plans could benefit consumers. PMID:25561646

  5. Medicare's Hospital Compare quality reports appear to have slowed price increases for two major procedures.

    PubMed

    Dor, Avi; Encinosa, William E; Carey, Kathleen

    2015-01-01

    Previous research has found that Hospital Compare, Medicare's public reporting initiative, has had little impact on patient outcomes. However, little is known about the initiative's impact on hospital prices, which may be significant because private insurers are generally well positioned to respond to quality information when negotiating prices with hospitals. We estimated difference-in-differences models of the effects of Hospital Compare quality reporting on transaction prices for two major cardiac procedures, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). States that had mandated their own public reporting systems before the implementation of Hospital Compare formed the control group. We found that prices for these procedures continued to increase overall after the initiation of Hospital Compare quality scores, but the rate of increase was significantly lower in states with no quality reporting metrics of their own before Hospital Compare, when compared to the control states (annual rates of increase of 4.4 percent versus 8.7 percent for PCI, and 3.9 percent versus 10.6 percent for CABG, adjusted for overall inflation). This finding implies that Hospital Compare provided leverage to purchasers in moderating price increases, while adding competitive pressures on hospitals. Providing accurate quality information on both hospitals and health plans could benefit consumers.

  6. The comparative mind-set: from animal comparisons to increased purchase intentions.

    PubMed

    Xu, Alison Jing; Wyer, Robert S

    2008-09-01

    Stimulating people to state a preference for one of two commercial products can increase their willingness to purchase not only one of these products, but also other products in a totally unrelated domain. However, willingness to make a purchase in a given domain (e.g., computers) can also be increased by asking individuals (a) to indicate which of two stimuli in a different domain (e.g., vacation packages) they dislike more, (b) to compare the relative attractiveness of wild animals, (c) to compare the animals with respect to physical attributes, and (d) to estimate how similar one object is to another. Moreover, the effects generalize to decisions about dating partners, as well as consumer products. In short, making any type of comparative judgment appears likely to give rise to a comparative-judgment mind-set and, therefore, to influence decisions in subsequent situations. PMID:18947350

  7. Increased Lung Volume in Infants and Toddlers at High Compared to Low Altitude

    PubMed Central

    Llapur, Conrado J.; Martínez, Myriam R.; Caram, María Marta; Bonilla, Federico; Cabana, Celia; Yu, Zhansheng; Tepper, Robert S.

    2015-01-01

    Summary Children and adults residing at high altitude (HA) compared to low altitude (LA) have larger lung volumes; however, it is unknown whether this response to chronic hypoxia begins early in life. Our objective was to determine whether infants and toddlers at HA have larger lung volumes compared to infants and toddlers at LA. Oxygen saturation (SaO2), functional residual capacity (FRC), as well as serum levels of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) were measured in infants and toddlers from HA (N = 50; 3,440 m) and LA (N = 35; 440 m). There were no significant differences in somatic size for HA and LA subjects; however, HA subjects had significantly lower SaO2 (88.5% vs. 96.7%; P < 0.0001). Subjects at HA had significantly greater FRC compared to subjects at LA (group mean: 209 and 157 ml; P < 0.0001), adjusting for body length. Male infants at HA had a significantly greater FRC compared to males at LA (57 ml; P-value < 0.001); however, the increase in FRC for females at HA compared to LA was not significant (20 ml; P-value = 0.101). VEGF and EPO were significantly higher for subjects at HA compared to LA with no gender differences. In summary, infants and toddlers at HA have lower oxygen saturations, higher serum levels of VEGF and EPO, and higher FRC compared to subjects at LA; however, chronic hypoxia appears to generate a more robust response in lung growth in male compared to female infants early in life. PMID:23401418

  8. Non-infected hemodialysis catheters are associated with increased inflammation compared to arteriovenous fistulas.

    PubMed

    Goldstein, Stuart L; Ikizler, T Alp; Zappitelli, Michael; Silverstein, Douglas M; Ayus, Juan C

    2009-11-01

    Although hemodialysis catheters predispose to infection which, in turn, causes inflammation, we studied whether they induce inflammation independent of infection. We compared the level of the inflammatory marker C-reactive protein (CRP) in maintenance hemodialysis patients, comparing those dialyzed using a non-infected catheter to those using arteriovenous fistulas. All incident patients had catheters and fistula placement at dialysis initiation. In 35 patients the fistulas matured, the catheters were removed and the patients were evaluated at 6 months (catheter-fistula). These results were compared to 15 patients in whom the fistula did not mature and catheter use persisted for 6 months (catheter-catheter). There was a significant 82% reduction in the CRP level in the catheter-fistula group but a 16% increase in the catheter-catheter group at 6 months. The changes in CRP did not differ by gender, diabetes status, or by race, and was not correlated with a change in phosphorus, age, or urea reduction ratio at 1 month following hemodialysis initiation. Decreased CRP was associated with increased hemoglobin and albumin. Patients with persistent fistula use from dialysis initiation through 6 months had consistently low CRP levels over that time period. Our study shows that catheters might contribute to increased inflammation independent of infection, and supports avoidance of catheters and a timely conversion to fistulas with catheter removal. PMID:19675528

  9. Increased error-related thalamic activity during early compared to late cocaine abstinence

    PubMed Central

    Li, Chiang-shan R.; Luo, Xi; Sinha, Rajita; Rounsaville, Bruce J.; Carroll, Kathleen M.; Malison, Robert T.; Ding, Yu-Shin; Zhang, Sheng; Ide, Jaime S.

    2010-01-01

    Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control. PMID:20163923

  10. Evidence for increased immune mobilization in First Episode Psychosis compared with the prodromal stage in males.

    PubMed

    Karanikas, Evangelos; Griveas, Ioannis; Ntouros, Evangelos; Floros, Georgios; Garyfallos, George

    2016-10-30

    The aim of the study was to gauge both the immune and neuroendocrine function in Ultra High Risk for psychosis (UHR) subjects and compare them with a cohort presenting with First Episode Psychosis (FEP). We recruited two groups, the first group consisted of 12 UHR males and the second of 25 males with FEP. We measured serum cortisol levels at 08:00, 12:00, 18:00 with their Area Under Curve with respect to the ground (AUCg) and the increase (AUCi) and we measured serum cytokines levels, Interleukin-1a, IL-1a, IL-2, IL-4,IL-5,IL-6,IL-8, IL-10,IL-12, IL-17a, Tumor Necrosis Factor-a (TNF-a), Interferon-γ (IFN-γ). Dexamethasone Suppression Test (DST) was also performed . The results suggest higher levels of both pro-inflammatory (TNF-a, IL-2, IL-12, IFN-γ) and anti-inflammatory (IL-10) cytokines in the FEP group compared with the UHR counterparts. Regarding the HPA axis function, the prodromal subjects showed a trend for higher AUCg and AUCi change/decrease cortisol levels. On the contrary, the DST results did not differ between the groups. No significant associations were demonstrated within each group among cytokines, cortisol and psychopathology. The findings favor a hypothesis of a relatively increased mobilization of both the pro- and anti-inflammatory cytokine networks, in FEP compared with that of UHR subjects. PMID:27517343

  11. Increased viable osteoblast density in the presence of nanophase compared to conventional alumina and titania particles.

    PubMed

    Gutwein, Luke G; Webster, Thomas J

    2004-08-01

    In the present in vitro study, osteoblast (bone-forming cells) viability and cell density were investigated when cultured in the presence of nanophase compared to conventional (i.e. micron) alumina and titania particles at various concentrations (from 10,000 to 100 microg/ml of cell culture media) for up to 6h. Results confirmed previous studies of the detrimental influences of all ceramic particulates on osteoblast viability and cell densities. For the first time, however, results provided evidence of increased apoptotic cell death when cultured in the presence of conventional compared to nanophase alumina and titania particles. Moreover, since material characterization studies revealed that the only difference between respective ceramic particles was nanometer- and conventional-dimensions (specifically, phase and chemical properties were similar between respective nanophase and conventional alumina as well as titania particles), these results indicated that osteoblast viability and densities were influenced solely by particle size. Such nanometer particulate wear debris may result from friction between articulating components of orthopedic implants composed of novel nanophase ceramic materials. Results of a less detrimental effect of nanometer--as compared to conventional-dimensioned particles on the functions of osteoblasts provide additional evidence that nanophase ceramics may become the next generation of bone prosthetic materials with increased efficacy and, thus, deserve further testing.

  12. Analysis of factors that increase motorcycle rider risk compared to car driver risk.

    PubMed

    Keall, Michael D; Newstead, Stuart

    2012-11-01

    As in other parts of the Western world, there is concern in New Zealand about increasing popularity of motorcycles because of potential increases in road trauma. This study sought to identify important factors associated with increased risk for motorcyclists to inform potential policy approaches to reduce motorcyclist injury, such as changes to motorcyclist licensing, training and education. Using data extracted from a register of all New Zealand licensed motor vehicles that were matched to crash data, statistical models were fitted to examine patterns of motorcycle risk in comparison with small cars. These showed generally elevated risks for motorcyclists compared to cars, but particularly elevated risks for motorcycle owners aged in their 20s or who lived in more urbanised settings. In crashes, motorcyclists have little protection from injury, putting the motorcyclist at high risk of injury. When comparing new motorcycles with new cars, the odds of fatal or serious injury to a motorcycle rider involved in an injury crash were almost eight times the odds for a car driver.

  13. Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone.

    PubMed

    Merouani, A; Davidson, S A; Schrier, R W

    1997-01-01

    To investigate the increased nephrotoxicity of taxol and cisplatin combination chemotherapy in gynecologic cancers as compared to cisplatin alone, the medical records of 25 patients with gynecological cancers were reviewed for evaluation of nephrotoxicity after chemotherapy treatment. The data included age, serum creatinine, calculated creatinine clearance, initial and cumulative dose of cisplatin and taxol, primary site of the cancer, renal ultrasound and hydration protocols. Renal function was evaluated before, during and 6 months after chemotherapy. Renal dysfunction was defined as a greater than 25% decrease in creatinine clearance. Comparing 11 patients treated with taxol and cisplatin versus 14 treated with cisplatin alone, there was a significant difference in effect on renal function. Nine of 11 patients (81%) treated with the combination chemotherapy had a greater than 25% decrease in creatinine clearance while only 4 of the 14 patients (29%) treated with cisplatin alone had such a decrease in creatinine clearance (p < 0.004). The patients treated with the combination chemotherapy, however, received a higher dose of cisplatin (80.4 vs. 66.4 mg/m2, p < 0.02) and were treated longer (6.7 vs. 4.3 months, p < 0.002). Nevertheless, when the patients were matched for age, initial dose and cumulative dose of cisplatin, a higher frequency of nephrotoxicity persisted in patients treated with taxol and cisplatin as compared to cisplatin alone (72 as compared to 20%, p < 0.02). The patients in both groups were comparably hydrated; prerenal failure and urinary tract obstruction were excluded in all patients. Six months after completion of chemotherapy, a significantly lower creatinine clearance was still observed in patients treated with taxol and cisplatin combination therapy (46 vs. 76 ml/min, p < 0.01). In summary, a retrospective analysis of renal function in patients with gynecological cancers showed an increased nephrotoxicity in patients treated with taxol and

  14. Dabigatran Use Does Not Increase Intracranial Hemorrhage in Traumatic Geriatric Falls When Compared with Warfarin.

    PubMed

    Pozzessere, Anthony; Grotts, Jonathan; Kaminski, Stephen

    2015-10-01

    Patients on anticoagulation are at increased risk for intracranial hemorrhage (ICH) after trauma. This is important for geriatric trauma patients, who are increasing in number, frequently fall, and often take anticoagulants. This study sought to evaluate whether prehospital use of dabigatran, a newer anticoagulant, is associated with outcome differences in geriatric trauma patients suffering falls when compared with warfarin. The registry of a Level II community trauma center was used to identify 247 patients aged 65 and older who sustained a fall while taking prehospital dabigatran or warfarin admitted between December 2010 and March 2014. Patients on warfarin were included if their International Normalized Ratio was therapeutic (2-3). About 176 of the 247 patients were then compared using coarsened exact matching. In the matched analysis, overall population means for age, Glasgow Coma Score, and Injury Severity Score were 83.5, 14.7, and 5.1, respectively. The overall rate of ICH was 12.5 per cent, with a mortality rate of 16.1 per cent for patients who sustained an ICH. There were no observed differences in ICH, hospital length of stay, intensive care unit length of stay, or mortality between patients taking prehospital warfarin or dabigatran.

  15. Transtibial amputee joint motion has increased attractor divergence during walking compared to non-amputee gait.

    PubMed

    Wurdeman, Shane R; Myers, Sara A; Stergiou, Nicholas

    2013-04-01

    The amputation and subsequent prosthetic rehabilitation of a lower leg affects gait. Dynamical systems theory would predict the use of a prosthetic device should alter the functional attractor dynamics to which the system self-organizes. Therefore, the purpose of this study was to compare the largest Lyapunov exponent (a nonlinear tool for assessing attractor dynamics) for amputee gait compared to healthy non-amputee individuals. Fourteen unilateral, transtibial amputees and fourteen healthy, non-amputee individuals ambulated on a treadmill at preferred, self-selected walking speed. Our results showed that the sound hip (p = 0.013), sound knee (p = 0.05), and prosthetic ankle (p = 0.023) have significantly greater largest Lyapunov exponents than healthy non-amputees. Furthermore, the prosthetic ankle has a significantly greater (p = 0.0.17) largest Lyapunov exponent than the sound leg ankle. These findings indicate attractor states for amputee gait with increased divergence. The increased attractor divergence seems to coincide with decreased ability for motor control between the natural rhythms of the individual and those of the prosthetic device. Future work should consider the impact of different prostheses and rehabilitation on the attractor dynamics.

  16. Increased frontal electroencephalogram theta amplitude in patients with anorexia nervosa compared to healthy controls

    PubMed Central

    Hestad, Knut A; Weider, Siri; Nilsen, Kristian Bernhard; Indredavik, Marit Sæbø; Sand, Trond

    2016-01-01

    Objective To conduct a blind study of quantitative electroencephalogram-band amplitudes in patients with anorexia nervosa (AN) and healthy controls. Methods Twenty-one patients with AN and 24 controls were examined with eyes-closed 16-channel electroencephalogram. Main variables were absolute alpha, theta, and delta amplitudes in frontal, temporal, and posterior regions. Results There were no significant differences between the AN patients and controls regarding absolute regional band amplitudes in μV. Borderline significance was found for anterior theta (P=0.051). Significantly increased left and right frontal electrode theta amplitude was found in AN patients (F3, P=0.014; F4, P=0.038) compared to controls. Significant differences were also observed for secondary variables: lower values for relative parietooccipital delta and frontocentral alpha activity among AN patients than among controls. Conclusion We observed slight excess frontal theta and lower relative alpha and delta amplitudes among AN patients than among controls. This pattern is possibly related to a slight frontal lobe dysfunction in AN, or it may reflect increased attention/vigilance or another state-related change in patients with AN compared to healthy controls. PMID:27703359

  17. Comparative Effectiveness of After-School Programs to Increase Physical Activity

    PubMed Central

    Gesell, Sabina B.; Sommer, Evan C.; Lambert, E. Warren; Vides de Andrade, Ana Regina; Davis, Lauren; Beech, Bettina M.; Mitchell, Stephanie J.; Neloms, Stevon; Ryan, Colleen K.

    2013-01-01

    Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7). Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P < .001). Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program. PMID:23984052

  18. Increased Risk of Revision after ACL Reconstruction with Soft Tissue Allograft Compared to Autograft

    PubMed Central

    Maletis, Gregory; Chen, Jason; Inacio, Maria Carolina Secorun; Love, Rebecca; Funahashi, Tadashi Ted

    2016-01-01

    Objectives: The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. Numerous meta-analysis and systematic reviews of small clinical studies have not found differences between autograft and allograft outcomes but large registry studies have shown an increased risk of revision with allografts. The purpose of this study was to compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts, hamstring tendon autografts and soft tissue allografts. Methods: A retrospective cohort study of prospectively collected data was conducted using an US ACLR Registry. A cohort of primary unilateral ACLR cases reconstructed with BPTB autografts, hamstring autografts and soft tissue allografts (from any site) was identified. Aseptic revision was the end point of the study. Type of graft and allograft processing methods (non-processed, <1.8Mrads with and without chemical processing (Allowash or AlloTrue methods), >1.8 Mrads irradiation with and without chemical processing, and chemical processing alone (BioCleanse)) were the exposures of interest evaluated. Time from surgery was evaluated as an effect modifier. All analyses were adjusted for age, gender, and race. Kaplan-Meier curves and Cox proportional hazard models were employed. Hazard ratios (HR), 95% confidence intervals (CI) are provided. Results: The cohort had 14015 cases, 8924 (63.7%) were male, 6397 (45.6%) were White, 4557 (32.5%) cases used BPTB autograft, 3751 (26.8%) cases used soft tissue allograft and 5707 (40.7%) cases used hamstring autograft. The median age was 34.6 years-old (IQR 24.1-43.2) for allograft cases and 24.3 years-old (IQR 17.7-33.8) for hamstring autograft cases, and 22.0 years-old (IQR 17.6-30.0) for BPTB autograft cases. Compared to hamstring tendon autografts, an increased risk of revision was found in allografts processed with >1.8Mrads without chemical processing after 2.5 years (HR: 3.88 95%CI 1.48-10.12), and >1.8Mrads with

  19. Social Behaviors Increase in Children with Autism in the Presence of Animals Compared to Toys

    PubMed Central

    O'Haire, Marguerite E.; McKenzie, Samantha J.; Beck, Alan M.; Slaughter, Virginia

    2013-01-01

    Background Previous research has demonstrated the capacity of animal presence to stimulate social interaction among humans. The purpose of this study was to examine the interactions of children with autism spectrum disorder (ASD) with an adult and their typically-developing peers in the presence of animals (two guinea pigs) compared to toys. Methods Ninety-nine children from 15 classrooms in 4 schools met the inclusion criteria and participated in groups of three (1 child with ASD and 2 typically-developing peers). Each group was video-recorded during three 10-minute, free-play sessions with toys and three 10-minute, free-play sessions with two guinea pigs. Two blinded observers coded the behavior of children with ASD and their peers. To account for the nested study design, data were analyzed using hierarchical generalized linear modeling. Results Participants with ASD demonstrated more social approach behaviors (including talking, looking at faces, and making tactile contact) and received more social approaches from their peers in the presence of animals compared to toys. They also displayed more prosocial behaviors and positive affect (i.e., smiling and laughing) as well as less self-focused behaviors and negative affect (i.e., frowning, crying, and whining) in the presence of animals compared to toys. Conclusions These results suggest that the presence of an animal can significantly increase positive social behaviors among children with ASD. PMID:23468902

  20. Comparing Canadian and American cybersecurity awareness levels: Educational strategies to increase public awareness

    NASA Astrophysics Data System (ADS)

    Hoggard, Amy

    Cybersecurity awareness is an important issue that affects everyone who uses a computer or a mobile device. Canada and the United States both recognize the value of mitigating cybersecurity risks in terms of national safety, economic stability and protection of their citizens. The research performed compared the levels of cybersecurity awareness in Canadian and American Internet users. Canadian and American users were equally aware of cybersecurity measures, but were not implementing best practices to keep themselves safe. The research suggested users needed to understand why a cybersecurity measure was important before being motivated to implement it. Educational strategies were reviewed in both Canada and the United States and it was determined that although there were significant resources available, they were not being utilized by both the educators and the public. In order to increase cybersecurity awareness levels, nations should focus on increasing the public's awareness by using various types of messaging, such as cartoons, in media. One possible consideration is a compulsory awareness model before accessing the Internet. Cybersecurity topics should be included in the curriculum for students at all levels of education and a focus on providing training and resources to teachers will help increase the cybersecurity knowledge of children and youth.

  1. Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

    SciTech Connect

    Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta; Benach, Jordi; Riera, Antoni; Pous, Joan; Macias, Maria J.

    2015-04-01

    Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.

  2. Evaluation of a randomized intervention to increase adoption of comparative effectiveness research by community health organizations.

    PubMed

    Williams, Jessica Roberts; Williams, Weston O; Dusablon, Tracy; Blais, Marissa Puckett; Tregear, Stephen J; Banks, Duren; PhD, Kevin D Hennessy

    2014-07-01

    This randomized controlled trial examined the influence of two strategies (informational packets alone and in conjunction with Webinars) aimed at increasing the adoption of motivational interviewing (MI), a patient-centered behavioral health practice supported by evidence from comparative effectiveness studies, among community health organizations responsible for delivering mental and behavioral health services. Data were obtained from 311 directors and staff across 92 community organizations. Hierarchical linear modeling was used to examine changes in decision to adopt MI. The mediating effects of multiple contextual variables were also examined. Results showed that both strategies positively influenced the decision to adopt. The positive impact on decision to adopt was significantly greater among individuals that received informational packets in conjunction with Webinars. Baseline attitudes toward evidence-based practices and pressures for change appeared to mediate this effect. PMID:24091611

  3. Comparative expression study to increase the solubility of cold adapted Vibrio proteins in Escherichia coli.

    PubMed

    Niiranen, Laila; Espelid, Sigrun; Karlsen, Christian R; Mustonen, Milla; Paulsen, Steinar M; Heikinheimo, Pirkko; Willassen, Nils P

    2007-03-01

    Functional and structural studies require gene overexpression and purification of soluble proteins. We wanted to express proteins from the psychrophilic bacterium Vibrio salmonicida in Escherichia coli, but encountered solubility problems. To improve the solubility of the proteins, we compared the effects of six N-terminal fusion proteins (Gb1, Z, thioredoxin, GST, MBP and NusA) and an N-terminal His6-tag. The selected test set included five proteins from the fish pathogen V. salmonicida and two related products from the mesophilic human pathogen Vibrio cholerae. We tested the expression in two different expression strains and at three different temperatures (16, 23 and 37 degrees C). His6-tag was the least effective tag, and these vector constructs were also difficult to transform. MBP and NusA performed best, expressing soluble proteins with all fusion partners in at least one of the cell types. In some cases MBP, GST and thioredoxin fusions resulted in products of incorrect size. The effect of temperature is complex: in most cases level of expression increased with temperature, whereas the effect on solubility was opposite. We found no clear connection between the preferred expression temperature of the protein and the temperature of the original host organism's natural habitat.

  4. Pet veterinarians have no increased risk of hepatitis E compared to the general population.

    PubMed

    Mesquita, J R; Valente-Gomes, G; Conceição-Neto, N; Nascimento, M S J

    2014-06-01

    The discovery of autochthonous hepatitis E in industrialized countries associated to genotype 3 has changed substantially the understanding about hepatitis E virus (HEV) circulation. In these countries transmission has been associated to the consumption and direct contact to swine, a well-known reservoir for HEV. More animal reservoirs for HEV might exist since antibodies to HEV have been detected in other animal species, such as dogs and cats. Given the intimate contact between these pets and humans, the potential zoonotic HEV transmission from dogs and cats deserves to be explored. To address this issue, 493 sera from pet veterinarians (373) and matched general population (120) were tested for the presence of anti-HEV IgG using a commercial ELISA. Antibodies to HEV were found in 9.9% veterinarians and 13.3% general population. No statistically significant difference was found between these two groups showing that pet veterinarians have no increased risk to hepatitis E compared to the general population. PMID:24610550

  5. Atomic Scale coexistence of Periodic and quasiperiodic order in a2-fold A1-Ni-Co decagonal quasicrystal surface

    SciTech Connect

    Park, Jeong Young; Ogletree, D. Frank; Salmeron, Miquel; Ribeiro,R.A.; Canfield, P.C.; Jenks, C.J.; Thiel, P.A.

    2005-11-14

    Decagonal quasicrystals are made of pairs of atomic planes with pentagonal symmetry periodically stacked along a 10-fold axis. We have investigated the atomic structure of the 2-fold surface of a decagonal Al-Ni-Co quasicrystal using scanning tunneling microscopy (STM). The surface consists of terraces separated by steps of heights 1.9, 4.7, 7.8, and 12.6{angstrom} containing rows of atoms parallel to the 10-fold direction with an internal periodicity of 4{angstrom}. The rows are arranged aperiodically, with separations that follow a Fibonacci sequence and inflation symmetry. The results indicate that the surfaces are preferentially Al-terminated and in general agreement with bulk models.

  6. Comparing the Effectiveness of Two Dance Game Interventions for Increasing Physical Movement and Intensity

    ERIC Educational Resources Information Center

    Tarbay, Joshua J.

    2011-01-01

    The problem addressed in this study was the increasing number of overweight and obese children and the increased demand for cost-effective methods of combating this epidemic. One method used to promote weight loss and to increase movement levels and cardiovascular endurance among school-aged children, is the Konami [R] brand dancing game, Dance…

  7. Comparing Two Classwide Interventions: Implications of Using Technology for Increasing Multiplication Fact Fluency

    ERIC Educational Resources Information Center

    Musti-Rao, Shobana; Plati, Erin

    2015-01-01

    An adapted alternating treatments design with initial baseline and final best treatment phase was used to evaluate and compare the effects of two classwide interventions, detect--practice--repair (DPR), and self-mediated iPad instruction, on the multiplication math facts fluency in an inclusive third-grade classroom. Twelve students participated…

  8. Comparing Different Classes of Reinforcement to Increase Expressive Language for Individuals with Autism

    ERIC Educational Resources Information Center

    Leaf, Justin B.; Dale, Stephanie; Kassardjian, Alyne; Tsuji, Kathleen H.; Taubman, Mitchell; McEachin, John J.; Leaf, Ronald B.; Oppenheim-Leaf, Misty L.

    2014-01-01

    One of the basic principles of applied behavior analysis is that behavior change is largely due to that behavior being reinforced. Therefore the use of positive reinforcement is a key component of most behavioral programs for individuals diagnosed with autism. In this study we compared four different classes of reinforcers (i.e., food, praise,…

  9. O-2 Substituted pyranosyl oxacarbenium ions are C-2-O-2 2-fold rotors with a strong syn preference.

    PubMed

    Ionescu, Andrei R; Whitfield, Dennis M; Zgierski, Marek Z

    2007-12-28

    The substituent at O-2 of glycopyranosides is known to have a pronounced effect on both the formation and the cleavage of glycosides at C-1. This is primarily attributed to stereoelectronic effects on the formation and stability of the related glycopyranosyl oxacarbenium ions. Previous QM studies of 2-O-methyl substituted manno and gluco configured pyranosyl oxacarbenium ions found a preference for the methyl carbon to be syn to the CH-2 methine. This study examines the conformational preference of variously substituted O-2 tetrahydropyranosyl oxacarbenium ions and confirms this syn preference. Neutral analogues are shown to have the expected 3-fold rotation whereas the charged species exhibit 2-fold rotation about C-2-O-2. Natural bond order (NBO) calculations suggest that the dominant stabilizing interaction is a unimodal O-2 lone pair to C-1-O-5 pi-bond hyperconjugative interaction. This syn conformational preference has important implications for mimics of glycopyranosyl oxacarbenium ion transition states. It also suggests a conformational based mechanism that can be exploited to tune the reactivity of glycopyranosyl donors in the glycosylation reaction.

  10. Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease

    PubMed Central

    Ellingford, Jamie M.; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G.; Sergouniotis, Panagiotis I.; O'Sullivan, James; Lamb, Janine A.; Perveen, Rahat; Hall, Georgina; Newman, William G.; Bishop, Paul N.; Roberts, Stephen A.; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C.; Nemeth, Andrea H.; Black, Graeme C.M.

    2016-01-01

    Purpose To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Design Case series. Participants A total of 562 patients diagnosed with IRD. Methods We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Main Outcome Measures Diagnostic yield of genomic testing. Results Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15–45) uplift in diagnostic yield. Conclusions We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. PMID:26872967

  11. 3-way Networks: Application of Hypergraphs for Modelling Increased Complexity in Comparative Genomics

    DOE PAGES

    Weighill, Deborah A.; Jacobson, Daniel A.

    2015-03-27

    Herein we present and develop the theory of 3-way networks, a type of hypergraph in which each edge models relationships between triplets of objects as opposed to pairs of objects as done by standard network models. We explore approaches of how to prune these 3-way networks, illustrate their utility in comparative genomics and demonstrate how they find relationships which would be missed by standard 2-way network models using a phylogenomic dataset of 211 bacterial genomes.

  12. Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens.

    PubMed

    Cappelletti, Maurand; Wallen, Kim

    2016-02-01

    Both estradiol and testosterone have been implicated as the steroid critical for modulating women's sexual desire. By contrast, in all other female mammals only estradiol has been shown to be critical for female sexual motivation and behavior. Pharmaceutical companies have invested heavily in the development of androgen therapies for female sexual desire disorders, but today there are still no FDA approved androgen therapies for women. Nonetheless, testosterone is currently, and frequently, prescribed off-label for the treatment of low sexual desire in women, and the idea of testosterone as a possible cure-all for female sexual dysfunction remains popular. This paper places the ongoing debate concerning the hormonal modulation of women's sexual desire within a historical context, and reviews controlled trials of estrogen and/or androgen therapies for low sexual desire in postmenopausal women. These studies demonstrate that estrogen-only therapies that produce periovulatory levels of circulating estradiol increase sexual desire in postmenopausal women. Testosterone at supraphysiological, but not at physiological, levels enhances the effectiveness of low-dose estrogen therapies at increasing women's sexual desire; however, the mechanism by which supraphysiological testosterone increases women's sexual desire in combination with an estrogen remains unknown. Because effective therapies require supraphysiological amounts of testosterone, it remains unclear whether endogenous testosterone contributes to the modulation of women's sexual desire. The likelihood that an androgen-only clinical treatment will meaningfully increase women's sexual desire is minimal, and the focus of pharmaceutical companies on the development of androgen therapies for the treatment of female sexual desire disorders is likely misplaced. PMID:26589379

  13. Does Axillary Boost Increase Lymphedema Compared With Supraclavicular Radiation Alone After Breast Conservation?

    SciTech Connect

    Hayes, Shelly B. Freedman, Gary M.; Li Tianyu; Anderson, Penny R.; Ross, Eric

    2008-12-01

    Purpose: To determine independent predictors of lymphedema (LE) after breast radiotherapy and to quantify added risks of LE from regional node irradiation (RNI). Materials and Methods: A total of 2,579 women with T1-2, N 0-3, M0 breast cancer treated with breast conservation between 1970 and 2005 were studied. A total of 2,169 patients (84%) received radiation to the breast (B), 226 (8.8%) to the breast and supraclavicular LNs (B+SC), and 184 (7.1%) to the breast, supraclavicular LNs, and a posterior axillary boost (B+SC+PAB). Median follow-up was 81 months (range, 3-271). Results: Eighteen percent of patients developed LE. LE risks were as follows: 16% (B), 23% (B+SC), and 31% (B+SC+PAB) (p < 0.0001). LE severity was greater in patients who had RNI (p = 0.0002). On multivariate analysis, RT field (p < 0.0001), obesity index (p = 0.0157), systemic therapy (p = 0.0013), and number of LNs dissected (p < 0.0001) independently predicted for LE. In N1 patients, the addition of a SC to tangents (p < 0.0001) and the addition of a PAB to tangents (p = 0.0017) conferred greater risks of LE, but adding a PAB to B+SC RT did not (p = 0.8002). In the N2 patients, adding a PAB increased the risk of LE 4.5-fold over B+SC RT (p = 0.0011). Conclusions: LE predictors included number of LNs dissected, RNI, obesity index, and systemic therapy. LE risk increased when a SC or PAB were added in the N1 subgroup. In the N2 patients, a PAB increased the risk over B+SC. The decision to boost the axilla must be weighed against the increased risk of LE that it imposes.

  14. Increased amplitude of cutaneous reflexes during human running as compared to standing.

    PubMed

    Duysens, J; Tax, A A; Trippel, M; Dietz, V

    1993-06-11

    The amplitude of H-reflexes is decreased during walking as compared to standing and a further reduction is seen during running as compared to walking. Does a similar reduction occur for reflexes elicited by cutaneous stimulation? To answer this question, the electromyographic (EMG) responses in biceps femoris (BF) and tibialis anterior (TA) to a 20 ms train of 5 electrical pulses, were recorded. This stimulus was applied to the sural nerve at the ankle, either at 16 different phases of the step cycle in human volunteers running on a treadmill at 8 km/h or at different isometric contraction levels of TA and BF in the same subjects during standing, imitating the postures of different phases of the step cycle. The mean latency of the main responses in BF of all subjects was 76 ms. Similar responses (P2), with a latency of 79 ms were seen in TA in 6 of the 10 subjects. For a constant strength of stimulation (2 times perception threshold) during isometric contractions at different levels in early stance imitation, the mean reflex ratio's (reflex/background) of BF and TA responses were 1.07 and 0.53, respectively, while the ratio's for these 2 muscles during running were 1.78 and 1.1. The higher reflex ratio's in running were primarily due to the large facilitatory responses, which were present during most of the step cycle but rarely during voluntary contractions in the subjects during standing. At the end of the swing phase, however, the responses in BF and TA were predominantly suppressive, as were most of the responses to stimulation applied to the standing subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Deep sequencing increases hepatitis C virus phylogenetic cluster detection compared to Sanger sequencing.

    PubMed

    Montoya, Vincent; Olmstead, Andrea; Tang, Patrick; Cook, Darrel; Janjua, Naveed; Grebely, Jason; Jacka, Brendan; Poon, Art F Y; Krajden, Mel

    2016-09-01

    Effective surveillance and treatment strategies are required to control the hepatitis C virus (HCV) epidemic. Phylogenetic analyses are powerful tools for reconstructing the evolutionary history of viral outbreaks and identifying transmission clusters. These studies often rely on Sanger sequencing which typically generates a single consensus sequence for each infected individual. For rapidly mutating viruses such as HCV, consensus sequencing underestimates the complexity of the viral quasispecies population and could therefore generate different phylogenetic tree topologies. Although deep sequencing provides a more detailed quasispecies characterization, in-depth phylogenetic analyses are challenging due to dataset complexity and computational limitations. Here, we apply deep sequencing to a characterized population to assess its ability to identify phylogenetic clusters compared with consensus Sanger sequencing. For deep sequencing, a sample specific threshold determined by the 50th percentile of the patristic distance distribution for all variants within each individual was used to identify clusters. Among seven patristic distance thresholds tested for the Sanger sequence phylogeny ranging from 0.005-0.06, a threshold of 0.03 was found to provide the maximum balance between positive agreement (samples in a cluster) and negative agreement (samples not in a cluster) relative to the deep sequencing dataset. From 77 HCV seroconverters, 10 individuals were identified in phylogenetic clusters using both methods. Deep sequencing analysis identified an additional 4 individuals and excluded 8 other individuals relative to Sanger sequencing. The application of this deep sequencing approach could be a more effective tool to understand onward HCV transmission dynamics compared with Sanger sequencing, since the incorporation of minority sequence variants improves the discrimination of phylogenetically linked clusters.

  16. Mapping of sequences with 2-fold symmetry on the simian virus 40 genome: a photochemical crosslinking approach.

    PubMed Central

    Shen, C K; Hearst, J E

    1977-01-01

    Sequences with 2-fold axes of symmetry have been detected and mapped on the simian virus 40 (SV40) genome by their ability to form hairpin turns in single-stranded SV40 DNA. Supercoiled SV40 DNA (SV40 I) was digested with restriction enzymes EcoRI and HpaII. The resulting linear DNA molecules with lengths of the complete SV40 genome were then denatured and photochemically reacted with 4,5',8-trimethylpsoralen (trioxsalen) at 16.0 +/- 0.5 degrees and different ionic strengths. Secondary structures on the single-stranded SV40 DNA were crosslinked and their positions analyzed by electron microscopy. There were no observable hairpin turns on the denatured SV40 DNA when it was photoreacted in 1 mM Tris-HCl/0.1 mM EDTA at pH 7.0. In 20 mM NaCl, one specific hairpin turn was detected at 0.17 +/- 0.02 map units on the map of EcoRI-digested SV40 DNA, where the 3' ends of early 19S mRNA, late 19S mRNA, and 16S mRNA of SV40 have been mapped. In 30 mM NaCl there are five more major hairpin turns besides the most stable one. The centers of four of these specific hairpin turns were mapped at 0.26 +/- 0.02, 0.68 +/- 0.03, 0.84 +/- 0.02, and 0.94 +/- 0.01 units on the map of EcoRI-digested SV40. The fifth one is at or near the unique EcoRI cleavage site on SV40 DNA. The possible functions of these sequences are discussed in terms of the nature of the promoter sites, the replication origin, the processing of RNA precursors, and regulation at the translational level. Images PMID:193097

  17. A comparative study of actinide complexation in three ligand systems with increasing complexity

    NASA Astrophysics Data System (ADS)

    Jeanson, A.; Dahou, S.; Guillaumont, D.; Moisy, P.; Den Auwer, C.; Scheinost, A.; Hennig, C.; Vidaud, C.; Subra, G.; Solari, P. L.

    2009-11-01

    The complexation of thorium, neptunium and plutonium at oxidation state +IV with three ligands of increasing complexity has been investigated. These ligands are relevant for bio inorganic systems. The first ligand is the small nitrilotriacetic acid that often play the role of protecting ligands against hydrolysis. EXAFS results for the Th to Pu series have been correlated to quantum chemical calculations and show an homogeneous behavior of the actinide at oxidation state +IV. For larger ligands, steric effects may become significant and one can ask how the ligand may accommodate the large actinide cation coordination sphere. Model pentapeptides have been synthesized and tested as complexing agents. Comparison with NTA shows that the molecular arrangements are radically different. The third ligand system is transferrin, a diferric metalloptrotein that is well known to coordinate a large variety of cations from transition metals of f-elements. Metalloproteins bear primary, secondary and tertiary structures that all play a crucial role in bonding. At a given oxidation state (+IV), but for various atomic numbers (Th, Np, Pu) EXAFS data at the cation LIII edge exhibit significant coordination discrepancies that are related to a changes in protein geometry. In that sense, the metalloprotein may be viewed as a complex system.

  18. Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

    PubMed Central

    Bruijn, Sjoerd M.; Van Dieën, Jaap H.; Daffertshofer, Andreas

    2015-01-01

    Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG) during stabilized and normal walking. Subjects walked on a treadmill in two conditions, each lasting 10 min; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG) of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component (IC) analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e., lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability. PMID:26578937

  19. Pivot task increases knee frontal plane loading compared with sidestep and drop-jump

    PubMed Central

    CORTES, NELSON; ONATE, JAMES; LUNEN, BONNIE VAN

    2013-01-01

    The purpose of this study was to assess kinematic and kinetic differences between three tasks (drop-jump, sidestep cutting, and pivot tasks) commonly used to evaluate anterior cruciate ligament risk factors. Nineteen female collegiate soccer athletes from a Division I institution participated in this study. Participants performed a drop-jump task, and two unanticipated tasks, sidestep cutting and pivot. Repeated-measures analyses of variance were conducted to assess differences in the kinematic and kinetic parameters between tasks. The pivot task had lower knee flexion (−41.2 ± 8.8°) and a higher valgus angle (−7.6 ± 10.1°) than the sidestep (−53.9 ± 9.4° and −2.9 ± 10.0°, respectively) at maximum vertical ground reaction force. The pivot task (0.8 ± 0.3 multiples of body weight) had higher peak posterior ground reaction force than the drop-jump (0.3 ± 0.06 multiples of body weight) and sidestep cutting (0.3 ± 0.1 multiples of body weight), as well as higher internal varus moments (0.72 ± 0.3 N · m/kg · m) than the drop-jump (0.14 ± 0.07 N · m/kg · m) and sidestep (0.17 ± 0.5 N · m/kg · m) at peak stance. During the pivot task, the athletes presented a more erect posture and adopted strategies that may place higher loads on the knee joint and increase the strain on the anterior cruciate ligament. PMID:21086213

  20. Multicenter comparison of the ISO standard 20776-1 and the serial 2-fold dilution procedures to dilute hydrophilic and hydrophobic antifungal agents for susceptibility testing.

    PubMed

    Gomez-Lopez, Alicia; Arendrup, Maiken Cavling; Lass-Floerl, Cornelia; Rodriguez-Tudela, Juan-Luis; Cuenca-Estrella, Manuel

    2010-05-01

    A multicenter study was conducted to assess the accuracy of the ISO standard 20776-1 and the serial 2-fold dilution procedures for antifungal susceptibility testing. Fluconazole trays can be accurately prepared by following ISO and serial dilution schemes. However, itraconazole trays showed a significant lack of reproducibility that was independent of which method was followed.

  1. How to Inform: Comparing Written and Video Education Interventions to Increase Human Papillomavirus Knowledge and Vaccination Intentions in Young Adults

    ERIC Educational Resources Information Center

    Krawczyk, Andrea; Lau, Elsa; Perez, Samara; Delisle, Vanessa; Amsel, Rhonda; Rosberger, Zeev

    2012-01-01

    Objective: To compare the efficacy of 2 human papillomavirus (HPV) educational interventions on increasing HPV knowledge and vaccination intentions in college students. Participants: Male (n = 60) and female (n = 140) undergraduates (M[subscript age] = 20.4, SD = 2.3) recruited from a university in Montreal, Quebec, Canada, from October 2009 to…

  2. Serum cytokines are increased and circulating micronutrients are not altered in subjects with early compared to advanced knee osteoarthritis.

    PubMed

    Barker, Tyler; Rogers, Victoria E; Henriksen, Vanessa T; Aguirre, Dale; Trawick, Roy H; Rasmussen, G Lynn; Momberger, Nathan G

    2014-08-01

    Knee osteoarthritis (OA) is a leading cause of physical disability. At the early stage of knee OA, the increase in synovial fluid cytokine concentrations could contribute to the pathogenesis of OA by degrading articular cartilage. It is unknown, however, if inflammatory cytokines increase systemically at the early or advanced stage of knee OA. The systemic increase of inflammatory cytokines could be detrimental to the endogenous status of micronutrients that protect against excessive inflammation and cytokine-mediated events. The purpose of this study was to test the hypothesis that an increase in serum cytokines associate with a decrease in circulating micronutrients in subjects with early compared to advanced knee OA. Advanced knee OA subjects (n=14) displayed radiographic, pain, and muscular weakness symptoms of knee OA. Early knee OA subjects (n=14) were matched (age, gender, and body mass index) to the advanced OA group and displayed one or two of the aforementioned symptoms of knee OA. Inflammatory cytokines, vitamins C (ascorbic acid), D (25-hydroxyvitamin D), and E (α- and γ-tocopherols), and β-carotene were measured in fasting blood samples. In the early OA group, serum tumor necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-12, and IL-13 concentrations were significantly (all p<0.05) increased. Circulating ascorbic acid, 25-hydroxyvitamin D, α- and γ-tocopherol's, and β-carotene concentrations were not significantly different between groups. Based on these preliminary results, we conclude that the systemic increase of inflammatory cytokines is not associated with a decrease in circulating micronutrients in subjects with early compared to advanced knee OA.

  3. Increased chromosome aberration frequencies in the Bowen's patients compared to non-cancerous skin lesions individuals exposed to arsenic.

    PubMed

    Ghosh, Pritha; Banerjee, Mayukh; De Chaudhuri, Sujata; Das, Jayanta K; Sarma, Nilendu; Basu, Arindam; Giri, Ashok K

    2007-08-15

    Cytogenetic biomarkers are essential for assessing environmental exposure that can predict adverse human health effects such as cellular damage. Chromosomal aberrations are the most important cytogenetic end-points successfully used for the cancer risk assessment of populations occupationally or environmentally exposed to different toxic chemicals. Previous reports suggest that, increased frequency of chromosomal aberration (CA), in peripheral blood lymphocytes, is a predictor of cancer. Arsenic is a paradoxical human carcinogen, clastogen and aneugen. Despite of exposure at similar extent, only 15-20% of individuals show arsenic induced skin lesions including Bowen's disease (BD). Previously we have reported the significant increase in CA in the individuals with arsenic induced skin lesions when compared to individuals without any skin lesions, drinking arsenic contaminated water at similar extent. Presently, a matched case-control study was performed to examine whether biomarkers such as chromosomal aberrations can predict the development of arsenic induced Bowen's (in situ carcinoma) diseases. Chromosomal aberrations (both chromosome and chromatid types) and mitotic index were analyzed from the lymphocytes of 25 cases of Bowen's patient which was compared to matched control from the individuals with arsenic induced non-cancerous skin lesions such as raindrop pigmentation, keratosis of palm and sole, hypo and hyper pigmentation. Chromosomal aberrations/cell, chromosome type aberrations and total percentage of aberrant cells were significantly higher in cases compared to control (p<0.01). These results suggest that chromosomal aberrations can be used for cancer risk assessment of the population exposed to arsenic through drinking water.

  4. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    PubMed

    Elwood, J Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia.

  5. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10

    PubMed Central

    Elwood, J. Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000–05 and 2006–10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia. PMID:26938056

  6. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    PubMed

    Elwood, J Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia. PMID:26938056

  7. Increased occurrence of pesticide residues on crops grown in protected environments compared to crops grown in open field conditions.

    PubMed

    Allen, Gina; Halsall, Crispin J; Ukpebor, Justina; Paul, Nigel D; Ridall, Gareth; Wargent, Jason J

    2015-01-01

    Crops grown under plastic-clad structures or in greenhouses may be prone to an increased frequency of pesticide residue detections and higher concentrations of pesticides relative to equivalent crops grown in the open field. To test this we examined pesticide data for crops selected from the quarterly reports (2004-2009) of the UK's Pesticide Residue Committee. Five comparison crop pairs were identified whereby one crop of each pair was assumed to have been grown primarily under some form of physical protection ('protected') and the other grown primarily in open field conditions ('open'). For each pair, the number of detectable pesticide residues and the proportion of crop samples containing pesticides were statistically compared (n=100 s samples for each crop). The mean concentrations of selected photolabile pesticides were also compared. For the crop pairings of cabbage ('open') vs. lettuce ('protected') and 'berries' ('open') vs. strawberries ('protected') there was a significantly higher number of pesticides and proportion of samples with multiple residues for the protected crops. Statistically higher concentrations of pesticides, including cypermethrin, cyprodinil, fenhexamid, boscalid and iprodione were also found in the protected crops compared to the open crops. The evidence here demonstrates that, in general, the protected crops possess a higher number of detectable pesticides compared to analogous crops grown in the open. This may be due to different pesticide-use regimes, but also due to slower rates of pesticide removal in protected systems. The findings of this study raise implications for pesticide management in protected-crop systems.

  8. Increased occurrence of pesticide residues on crops grown in protected environments compared to crops grown in open field conditions.

    PubMed

    Allen, Gina; Halsall, Crispin J; Ukpebor, Justina; Paul, Nigel D; Ridall, Gareth; Wargent, Jason J

    2015-01-01

    Crops grown under plastic-clad structures or in greenhouses may be prone to an increased frequency of pesticide residue detections and higher concentrations of pesticides relative to equivalent crops grown in the open field. To test this we examined pesticide data for crops selected from the quarterly reports (2004-2009) of the UK's Pesticide Residue Committee. Five comparison crop pairs were identified whereby one crop of each pair was assumed to have been grown primarily under some form of physical protection ('protected') and the other grown primarily in open field conditions ('open'). For each pair, the number of detectable pesticide residues and the proportion of crop samples containing pesticides were statistically compared (n=100 s samples for each crop). The mean concentrations of selected photolabile pesticides were also compared. For the crop pairings of cabbage ('open') vs. lettuce ('protected') and 'berries' ('open') vs. strawberries ('protected') there was a significantly higher number of pesticides and proportion of samples with multiple residues for the protected crops. Statistically higher concentrations of pesticides, including cypermethrin, cyprodinil, fenhexamid, boscalid and iprodione were also found in the protected crops compared to the open crops. The evidence here demonstrates that, in general, the protected crops possess a higher number of detectable pesticides compared to analogous crops grown in the open. This may be due to different pesticide-use regimes, but also due to slower rates of pesticide removal in protected systems. The findings of this study raise implications for pesticide management in protected-crop systems. PMID:25465948

  9. Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum

    PubMed Central

    de Villiers, Sabina H.L.; Cornish, Katherine E.; Troska, Andrew J.; Pravetoni, Marco; Pentel, Paul R.

    2014-01-01

    Vaccination against nicotine is a potential treatment for tobacco smoking. Clinical trials show effect only in high antibody responders; therefore it is necessary to increase the effectiveness of nicotine vaccines. The use of a multivalent vaccine that activates several B cell populations is a possible approach to increase antibody response. The aim of this study was to investigate whether three different nicotine immunogens could be mixed to generate independent responses resulting in additive antibody titers, and whether this would alter nicotine distribution to a greater extent than antibodies generated by a monovalent vaccine. When immunogens were administered s.c. with alum adjuvant, the trivalent vaccine generated significantly higher titers and prevented the distribution of an i.v. nicotine dose to brain to a greater extent than an equivalent dose of a monovalent vaccine. The number of rats with antibody titers >1:10,000 was significantly increased in the trivalent group compared to the monovalent group. There were no correlations between the titers generated by the different nicotine immunogens in the trivalent vaccine, supporting the hypothesis that the immunogens generated independent responses from distinct populations of B cells. In contrast, when administered i.p. in Freund’s adjuvant, the trivalent nicotine vaccine was not more immunogenic than its component monovalent vaccine. Vaccine immunogenicity was suppressed if unconjugated protein was added to the monovalent vaccine formulated in Freund’s adjuvant, compared to monovalent vaccine alone. These data suggest a protein–protein interaction that affects titers negatively and is apparent when the vaccines are formulated with Freund’s adjuvant. In summary, a trivalent nicotine vaccine formulated with alum showed significantly higher efficacy than a dose-matched monovalent vaccine and may offer a strategy for increasing nicotine vaccine immunogenicity. This approach may be generalizable to other

  10. Ribosomal DNA transcription in dorsal raphe nucleus neurons is increased in residual schizophrenia compared to depressed patients with affective disorders.

    PubMed

    Krzyżanowska, Marta; Steiner, Johann; Brisch, Ralf; Mawrin, Christian; Busse, Stefan; Braun, Katharina; Jankowski, Zbigniew; Bernstein, Hans-Gert; Bogerts, Bernhard; Gos, Tomasz

    2015-12-15

    The central serotonergic system is implicated differentially in the pathogenesis of depression and schizophrenia. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in both disorders. The study was carried out on paraffin-embedded brains from 27 depressed (15 major depressive disorder, MDD and 12 bipolar disorder, BD) and 17 schizophrenia (9 residual and 8 paranoid) patients and 28 matched controls without mental disorders. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons was evaluated by the AgNOR silver staining method. A significant effect of diagnosis on rDNA activity was found in the cumulative analysis of all DRN subnuclei. Further analysis revealed an increase in this activity in residual (but not paranoid) schizophrenia compared to depressed (both MDD and BD) patients. The effect was most probably neither confounded by suicide nor related to antidepressant and antipsychotic medication. Our findings suggest that increased activity of rDNA in DRN neurons is a distinct phenomenon in residual schizophrenia, related presumably to differentially disturbed inputs to the DRN and/or their local transformation compared with depressive episodes in patients with affective disorders.

  11. Comparing tailored and narrative worksite interventions at increasing colonoscopy adherence in adults 50-75: a randomized controlled trial.

    PubMed

    Jensen, Jakob D; King, Andy J; Carcioppolo, Nick; Krakow, Melinda; Samadder, N Jewel; Morgan, Susan

    2014-03-01

    Research has identified several communication strategies that could increase adherence to colorectal cancer screening recommendations. Two promising strategies are tailoring and narrative-based approaches. Tailoring is the personalization of information based on individual characteristics. Narrative-based approaches use stories about similar others to counter perceived barriers and cultivate self-efficacy. To compare these two approaches, a randomized controlled trial was carried out at 8 worksites in Indiana. Adults 50-75 (N = 209) received one of four messages about colorectal cancer screening: stock, narrative, tailored, tailored narrative. The primary outcome was whether participants filed a colonoscopy claim in the 18 months following the intervention. Individuals receiving narrative messages were 4 times more likely to screen than those not receiving narrative messages. Tailoring did not increase screening behavior overall. However, individuals with higher cancer information overload were 8 times more likely to screen if they received tailored messages. The results suggest that narrative-based approaches are more effective than tailoring at increasing colorectal cancer screening in worksite interventions. Tailoring may be valuable as a strategy for reaching individuals with high overload, perhaps as a follow-up effort to a larger communication campaign.

  12. Increased serum concentrations of circulating glycocalyx components in HELLP syndrome compared to healthy pregnancy: an observational study.

    PubMed

    Hofmann-Kiefer, Klaus F; Knabl, J; Martinoff, N; Schiessl, B; Conzen, P; Rehm, M; Becker, B F; Chappell, D

    2013-03-01

    Severe inflammation has been shown to induce a shedding of the endothelial glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor α (TNF-α), impede the thickness of the EGX. While a controlled inflammatory reaction occurs already in normal pregnancy, women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory response. This study investigates the shedding of the glycocalyx during normal pregnancy and in women with HELLP syndrome. Glycocalyx components (syndecan 1, heparan sulfate, and hyaluronic acid) were measured in serum of healthy women throughout pregnancy (4 time points, n = 26), in women with HELLP syndrome (n = 17) before delivery and in nonpregnant volunteers (n = 10). Serum concentrations of TNF-α and soluble TNF-α receptors (sTNF-Rs) were assessed once in all 3 groups. Syndecan 1 serum concentrations constantly rose throughout normal pregnancy. Immediately before delivery, a 159-fold increase was measured compared to nonpregnant controls (P < .01). Even higher amounts were observed in patients with HELLP prior to delivery (median 12 252 ng/mL) compared to healthy women matched by gestational age (median 5943 ng/mL; P < .01). Relevantly, increased serum levels of heparan sulfate, hyaluronic acid, and sTNF-Rs were only detected in patients with HELLP (P < .01). These findings suggest that considerable amounts of syndecan 1 are released into maternal blood during uncomplicated pregnancy. The HELLP syndrome is associated with an even more pronounced shedding of glycocalyx components. The maternal vasculature as well as the placenta has to be discussed as a possible origin of circulating glycocalyx components.

  13. Moderate Glucose Control Is Associated With Increased Mortality Compared With Tight Glucose Control in Critically Ill Patients Without Diabetes

    PubMed Central

    Hirshberg, Eliotte L.; Phillips, Gregory D.; Holmen, John; Stoddard, Gregory; Orme, James

    2013-01-01

    Background: Optimal glucose management in the ICU remains unclear. In 2009, many clinicians at Intermountain Healthcare selected a moderate glucose control (90-140 mg/dL) instead of tight glucose control (80-110 mg/dL). We hypothesized that moderate glucose control would affect patients with and without preexisting diabetes differently. Methods: We performed a retrospective cohort analysis of all patients treated with eProtocol-insulin from November 2006 to March 2011, stratifying for diabetes. We performed multivariate logistic regression for 30-day mortality with covariates of age, modified APACHE (Acute Physiology and Chronic Health Evaluation) II score, Charlson Comorbidity score, and target glucose. Results: We studied 3,529 patients in 12 different ICUs in eight different hospitals. Patients with diabetes had higher mean glucose (132 mg/dL vs 124 mg/dL) and greater glycemic variability (SD = 41 mg/dL vs 29 mg/dL) than did patients without diabetes (P < .01 for both comparisons). Tight glucose control was associated with increased frequency of moderate and severe hypoglycemia (30.3% and 3.6%) compared with moderate glucose control (14.3% and 2.0%, P < .01 for both). Multivariate analysis demonstrated that the moderate glucose target was independently associated with increased risk of mortality in patients without diabetes (OR, 1.36; 95% CI, 1.01-1.84; P = .05) but decreased risk of mortality in patients with diabetes (OR, 0.65; 95% CI, 0.45-0.93; P = .01). Conclusions: Moderate glucose control (90-140 mg/dL) may confer greater mortality in critically ill patients without diabetes compared with tight glucose control (80-110 mg/dL). A single glucose target does not appear optimal for all critically ill patients. These data have important implications for the design of future interventional trials as well as for the glycemic management of critically ill patients. PMID:23238456

  14. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones

    PubMed Central

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones. PMID:27555864

  15. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones.

    PubMed

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones. PMID:27555864

  16. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones.

    PubMed

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones.

  17. Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

    PubMed

    Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

    2015-06-01

    Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

  18. Increasing fruit and vegetable intake among children: comparing long-term effects of a free distribution and a multicomponent program.

    PubMed

    Reinaerts, E; Crutzen, R; Candel, M; De Vries, N K; De Nooijer, J

    2008-12-01

    The aim of this study was to evaluate and compare the effectiveness of two primary school-based interventions on children's fruit and vegetable (F&V) consumption on the long term (2 years after the start of the interventions). Six primary schools were recruited and randomly assigned to (i) a daily free distribution program for the whole school or (ii) a multicomponent program consisting of a classroom curriculum and parental involvement (without free F&V), and six schools served as controls. Follow-up measurements were conducted at the end of the intervention (Follow-up I) and 1 year later (Follow-up II). Random coefficient analyses for longitudinal data showed that the effects of both interventions did not differ between the two follow-up measurements. The results showed similar effects for the free distribution program and the multicomponent program in increasing children's fruit consumption over time (respectively, 7.2 and 15.2 g day(-1)). The distribution program also increased children's vegetable consumption over time (3.25 g day(-1)), even after repeating the analyses using a pessimistic scenario. Despite the large dropout and its consequences for generalizability of our results, the distribution program is considered as the preferred intervention of the two, and implementation on a larger scale should be investigated.

  19. Increased brain response to appetitive tastes in the insula and amygdala in obese compared to healthy weight children when sated

    PubMed Central

    Boutelle, Kerri; Wierenga, Christina E; Bischoff-Grethe, Amanda; Melrose, Andrew James; Grenesko-Stevens, Emily; Paulus, Martin P; Kaye, Walter H

    2015-01-01

    Objective There is evidence of altered neural taste response in female adolescents who are obese, and in adolescents who are at risk for obesity. To further understand risk factors for the development of overeating and obesity, we investigated response to tastes of sucrose and water in 23 obese and healthy weight children. Methods and design Thirteen healthy weight (HW) and 10 obese (OB) 8–12 year old children underwent functional magnetic resonance imaging while tasting sucrose and water. Additionally, children completed an eating in the absence of hunger paradigm and a sucrose liking task. Results A region of interest analysis revealed an elevated BOLD response to taste (sucrose and water) within the bilateral insula and amygdala in OB children relative to HW children. Whole brain analyses revealed a group by condition interaction within the paracingulate, medial frontal, middle frontal gyri, and right amygdala: post hoc analyses suggested an increased response to sucrose for OB relative to HW children, whereas HW children responded more strongly to water relative to sucrose. In addition, OB children, relative to HW, tended to recruit the right putamen as well as medial and lateral frontal and temporal regions bilaterally. Conclusion This study showed increased reactivity in the amygdala and insula in the OB compared to HW children, but no functional differentiation in the striatum, despite differences in the striatum previously seen in older samples. These findings support the concept of the association between increased neural processing of food reward in the development of obesity, and raise the possibility that emotional and interoceptive sensitivity could be an early vulnerability in obesity. PMID:25582522

  20. Daily irrigation attenuates xylem abscisic acid concentration and increases leaf water potential of Pelargonium × hortorum compared with infrequent irrigation.

    PubMed

    Boyle, Richard K A; McAinsh, Martin; Dodd, Ian C

    2016-09-01

    The physiological response of plants to different irrigation frequencies may affect plant growth and water use efficiency (WUE; defined as shoot biomass/cumulative irrigation). Glasshouse-grown, containerized Pelargonium × hortorum BullsEye plants were irrigated either daily at 100% of plant evapotranspiration (ET) (well-watered; WW), or at 50% ET applied either daily [frequent deficit irrigation (FDI)] or cumulatively every 4 days [infrequent deficit irrigation (IDI)], for 24 days. Both FDI and IDI applied the same irrigation volume. Xylem sap was collected from the leaves, and stomatal conductance (gs ) and leaf water potential (Ψleaf ) measured every 2 days. As soil moisture decreased, gs decreased similarly under both FDI and IDI throughout the experiment. Ψleaf was maintained under IDI and increased under FDI. Leaf xylem abscisic acid (ABA) concentrations ([X-ABA]leaf ) increased as soil moisture decreased under both IDI and FDI, and was strongly correlated with decreased gs , but [X-ABA]leaf was attenuated under FDI throughout the experiment (at the same level of soil moisture as IDI plants). These physiological changes corresponded with differences in plant production. Both FDI and IDI decreased growth compared with WW plants, and by the end of the experiment, FDI plants also had a greater shoot fresh weight (18%) than IDI plants. Although both IDI and FDI had higher WUE than WW plants during the first 10 days of the experiment (when biomass did not differ between treatments), the deficit irrigation treatments had lower WUE than WW plants in the latter stages when growth was limited. Thus, ABA-induced stomatal closure may not always translate to increased WUE (at the whole plant level) if vegetative growth shows a similar sensitivity to soil drying, and growers must adapt their irrigation scheduling according to crop requirements.

  1. Daily irrigation attenuates xylem abscisic acid concentration and increases leaf water potential of Pelargonium × hortorum compared with infrequent irrigation.

    PubMed

    Boyle, Richard K A; McAinsh, Martin; Dodd, Ian C

    2016-09-01

    The physiological response of plants to different irrigation frequencies may affect plant growth and water use efficiency (WUE; defined as shoot biomass/cumulative irrigation). Glasshouse-grown, containerized Pelargonium × hortorum BullsEye plants were irrigated either daily at 100% of plant evapotranspiration (ET) (well-watered; WW), or at 50% ET applied either daily [frequent deficit irrigation (FDI)] or cumulatively every 4 days [infrequent deficit irrigation (IDI)], for 24 days. Both FDI and IDI applied the same irrigation volume. Xylem sap was collected from the leaves, and stomatal conductance (gs ) and leaf water potential (Ψleaf ) measured every 2 days. As soil moisture decreased, gs decreased similarly under both FDI and IDI throughout the experiment. Ψleaf was maintained under IDI and increased under FDI. Leaf xylem abscisic acid (ABA) concentrations ([X-ABA]leaf ) increased as soil moisture decreased under both IDI and FDI, and was strongly correlated with decreased gs , but [X-ABA]leaf was attenuated under FDI throughout the experiment (at the same level of soil moisture as IDI plants). These physiological changes corresponded with differences in plant production. Both FDI and IDI decreased growth compared with WW plants, and by the end of the experiment, FDI plants also had a greater shoot fresh weight (18%) than IDI plants. Although both IDI and FDI had higher WUE than WW plants during the first 10 days of the experiment (when biomass did not differ between treatments), the deficit irrigation treatments had lower WUE than WW plants in the latter stages when growth was limited. Thus, ABA-induced stomatal closure may not always translate to increased WUE (at the whole plant level) if vegetative growth shows a similar sensitivity to soil drying, and growers must adapt their irrigation scheduling according to crop requirements. PMID:26910008

  2. Decreased blood antioxidant capacity and increased lipid peroxidation in young cigarette smokers compared to nonsmokers: Impact of dietary intake

    PubMed Central

    Bloomer, Richard J

    2007-01-01

    Background Blood of cigarette smokers routinely displays decreased antioxidant capacity and increased oxidized lipids compared to nonsmokers. This is thought to be due to both chronic exposure to cigarette smoke in addition to low intake of dietary antioxidants, and is a routine finding in veteran smokers. No study to date has determined the independent and combined impact of dietary intake and cigarette smoking on blood antioxidant capacity and oxidative stress in a sample of young, novice smokers. Methods We compared resting plasma antioxidant reducing capacity (ARC; expressed in uric acid equivalents), serum trolox-equivalent antioxidant capacity (TEAC), whole blood total glutathione, plasma malondialdehyde (MDA), and plasma oxidized low density lipoprotein (oxLDL) between 15 young (24 ± 4 years), novice smokers (pack-year history: 3 ± 2) and 13 nonsmokers of similar age (24 ± 5 years). Detailed dietary records were maintained during a seven-day period for analysis of total energy, macro- and micronutrient intake. Results ARC (0.0676 ± 0.0352 vs. 0.1257 ± 0.0542 mmol·L-1; mean ± SD, p = 0.019), TEAC (0.721 ± 0.120 vs. 0.765 ± 0.130 mmol·L-1, p = 0.24) and glutathione (835 ± 143 vs. 898 ± 168 μmol·L-1, p = 0.28) were lower in smokers compared to nonsmokers, with only the former being statistically significant. MDA (0.919 ± 0.32 vs. 0.647 ± 0.16 μmol·L-1, p = 0.05) and oxLDL were both higher in smokers compared to nonsmokers (229 ± 94 vs. 110 ± 62 ng·mL-1, p = 0.12), although only the MDA comparison was of statistical significance. Interestingly, these findings existed despite no differences in dietary intake, including antioxidant micronutrient consumption, between both smokers and nonsmokers. Conclusion These data, with specificity to young, novice cigarette smokers, underscore the importance of smoking abstinence. Future studies with larger sample sizes, inclusive of smokers of different ages and smoking histories, are needed to extend

  3. Comparable Cerebral Oxygenation Patterns in Younger and Older Adults during Dual-Task Walking with Increasing Load

    PubMed Central

    Fraser, Sarah A.; Dupuy, Olivier; Pouliot, Philippe; Lesage, Frédéric; Bherer, Louis

    2016-01-01

    The neuroimaging literature on dual-task gait clearly demonstrates increased prefrontal cortex (PFC) involvement when performing a cognitive task while walking. However, findings from direct comparisons of the cerebral oxygenation patterns of younger (YA) and older (OA) adults during dual-task walking are mixed and it is unclear how YA and OA respond to increasing cognitive load (difficulty) while walking. This functional near infra-red (fNIRS) study examined cerebral oxygenation of YA and OA during self-paced dual-task treadmill walking at two different levels of cognitive load (auditory n-back). Changes in accuracy (%) as well as oxygenated (HbO) and deoxygenated (HbR) hemoglobin were examined. For the HbO and HbR measures, eight regions of interest (ROIs) were assessed: the anterior and posterior dorsolateral and ventrolateral PFC (aDLPFC, pDLPFC, aVLPFC, pVLPFC) in each hemisphere. Nineteen YA (M = 21.83 years) and 14 OA (M = 66.85 years) walked at a self-selected pace while performing auditory 1-back and 2-back tasks. Walking alone (single motor: SM) and performing the cognitive tasks alone (single cognitive: SC) were compared to dual-task walking (DT = SM + SC). In the behavioural data, participants were more accurate in the lowest level of load (1-back) compared to the highest (2-back; p < 0.001). YA were more accurate than OA overall (p = 0.009), and particularly in the 2-back task (p = 0.048). In the fNIRS data, both younger and older adults had task effects (SM < DT) in specific ROIs for ΔHbO (three YA, one OA) and ΔHbR (seven YA, eight OA). After controlling for walk speed differences, direct comparisons between YA and OA did not reveal significant age differences, but did reveal a difficulty effect in HbO in the left aDLPFC (p = 0.028) and significant task effects (SM < DT) in HbR for six of the eight ROIs. Findings suggest that YA and OA respond similarly to manipulations of cognitive load when walking on a treadmill at a self-selected pace. PMID

  4. Selenium-Enriched Foods Are More Effective at Increasing Glutathione Peroxidase (GPx) Activity Compared with Selenomethionine: A Meta-Analysis

    PubMed Central

    Bermingham, Emma N.; Hesketh, John E.; Sinclair, Bruce R.; Koolaard, John P.; Roy, Nicole C.

    2014-01-01

    Selenium may play a beneficial role in multi-factorial illnesses with genetic and environmental linkages via epigenetic regulation in part via glutathione peroxidase (GPx) activity. A meta-analysis was undertaken to quantify the effects of dietary selenium supplementation on the activity of overall GPx activity in different tissues and animal species and to compare the effectiveness of different forms of dietary selenium. GPx activity response was affected by both the dose and form of selenium (p < 0.001). There were differences between tissues on the effects of selenium supplementation on GPx activity (p < 0.001); however, there was no evidence in the data of differences between animal species (p = 0.95). The interactions between dose and tissue, animal species and form were significant (p < 0.001). Tissues particularly sensitive to changes in selenium supply include red blood cells, kidney and muscle. The meta-analysis identified that for animal species selenium-enriched foods were more effective than selenomethionine at increasing GPx activity. PMID:25268836

  5. Has increased clinical experience with methotrexate reduced the direct costs of medical management of ectopic pregnancy compared to surgery?

    PubMed Central

    2012-01-01

    Background There is a debate about the cost-efficiency of methotrexate for the management of ectopic pregnancy (EP), especially for patients presenting with serum human chorionic gonadotrophin levels of >1500 IU/L. We hypothesised that further experience with methotrexate, and increased use of guideline-based protocols, has reduced the direct costs of management with methotrexate. Methods We conducted a retrospective cost analysis on women treated for EP in a large UK teaching hospital to (1) investigate whether the cost of medical management is less expensive than surgical management for those patients eligible for both treatments and (2) to compare the cost of medical management for women with hCG concentrations 1500–3000 IU/L against those with similar hCG concentrations that elected for surgery. Three distinct treatment groups were identified: (1) those who had initial medical management with methotrexate, (2) those who were eligible for initial medical management but chose surgery (‘elected’ surgery) and (3) those who initially ‘required’ surgery and did not meet the eligibility criteria for methotrexate. We calculated the costs from the point of view of the National Health Service (NHS) in the UK. We summarised the cost per study group using the mean, standard deviation, median and range and, to account for the skewed nature of the data, we calculated 95% confidence intervals for differential costs using the nonparametric bootstrap method. Results Methotrexate was £1179 (CI 819–1550) per patient cheaper than surgery but there were no significant savings with methotrexate in women with hCG >1500 IU/L due to treatment failures. Conclusions Our data support an ongoing unmet economic need for better medical treatments for EP with hCG >1500 IU/L. PMID:22985126

  6. Comparative proteomics and glycoproteomics reveal increased N-linked glycosylation and relaxed sequon specificity in Campylobacter jejuni NCTC11168 O.

    PubMed

    Scott, Nichollas E; Marzook, N Bishara; Cain, Joel A; Solis, Nestor; Thaysen-Andersen, Morten; Djordjevic, Steven P; Packer, Nicolle H; Larsen, Martin R; Cordwell, Stuart J

    2014-11-01

    Campylobacter jejuni is a major cause of bacterial gastroenteritis. C. jejuni encodes a protein glycosylation (Pgl) locus responsible for the N-glycosylation of membrane-associated proteins. We examined two variants of the genome sequenced strain NCTC11168: O, a representative of the original clinical isolate, and GS, a laboratory-adapted relative of O. Comparative proteomics by iTRAQ and two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D-LC-MS/MS) allowed the confident identification of 1214 proteins (73.9% of the predicted C. jejuni proteome), of which 187 were present at statistically significant altered levels of abundance between variants. Proteins associated with the O variant included adhesins (CadF and FlpA), proteases, capsule biosynthesis, and cell shape determinants as well as six proteins encoded by the Pgl system, including the PglK flippase and PglB oligosaccharyltransferase. Lectin blotting highlighted specific glycoproteins more abundant in NCTC11168 O, whereas others remained unaltered. Hydrophilic interaction liquid chromatography (HILIC) and LC-MS/MS identified 30 completely novel glycosites from 15 proteins. A novel glycopeptide from a 14 kDa membrane protein (Cj0455c) was identified that did not contain the C. jejuni N-linked sequon D/E-X-N-X-S/T (X ≠ Pro) but that instead contained a sequon with leucine at the -2 position. Occupied atypical sequons were also observed in Cj0958c (OxaA; Gln at the -2 position) and Cj0152c (Ala at the +2 position). The relative O and GS abundances of 30 glycopeptides were determined by label-free quantitation, which revealed a >100-fold increase in the atypical glycopeptide from Cj0455c in isolate O. Our data provide further evidence for the importance of the Pgl system in C. jejuni.

  7. Gymnosperms have increased capacity for electron leakage to oxygen (Mehler and PTOX reactions) in photosynthesis compared with angiosperms.

    PubMed

    Shirao, Masayoshi; Kuroki, Shu; Kaneko, Kaoru; Kinjo, Yuriko; Tsuyama, Michito; Förster, Britta; Takahashi, Shunichi; Badger, Murray R

    2013-07-01

    Oxygen plays an important role in photosynthesis by participating in a number of O2-consuming reactions. O2 inhibits CO2 fixation by stimulating photorespiration, thus reducing plant production. O2 interacts with photosynthetic electron transport in the chloroplasts' thylakoids in two main ways: by accepting electrons from PSI (Mehler reaction); and by accepting electrons from reduced plastoquinone (PQ) mediated by the plastid terminal oxidase (PTOX). In this study, we show, using 101 plant species, that there is a difference in the potential for photosynthetic electron flow to O2 between angiosperms and gymnosperms. We found, from measurements of Chl fluorescence and leaf absorbance at 830 nm, (i) that electron outflow from PSII, as determined by decay kinetics of Chl fluorescence after application of a saturating light pulse, is more rapid in gymnosperms than in angiosperms; (ii) that the reaction center Chl of PSI (P700) is rapidly and highly oxidized in gymnosperms during induction of photosynthesis; and (iii) that these differences are dependent on oxygen. Finally, rates of O2 uptake measured by mass spectrometry in the absence of photorespiration were significantly promoted by illumination in dark-adapted leaves of gymnosperms, but not in those of angiosperms. The light-stimulated O2 uptake was around 10% of the maximum O2 evolution in gymnosperms and 1% in angiosperms. These results suggest that gymnosperms have increased capacity for electron leakage to oxygen in photosynthesis compared with angiosperms. The involvement of the Mehler reaction and PTOX in the electron flow to O2 is discussed.

  8. Increased platelet count and leucocyte–platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis

    PubMed Central

    McCabe, D; Harrison, P; Mackie, I; Sidhu, P; Purdy, G; Lawrie, A; Watt, H; Machin, S; Brown, M

    2005-01-01

    Objective: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. Methods: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte–platelet complexes in patients with acute (0–21 days, n = 19) and convalescent (79–365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (⩾70%) carotid stenosis. Most patients were treated with aspirin (37.5–300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. Results: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil–platelet (p = 0.004), monocyte–platelet (p = 0.046), and lymphocyte–platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil–platelet and monocyte–platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte–platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. Conclusion: Increased platelet count and leucocyte–platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis. PMID:16107361

  9. Mutants at the 2-Fold Interface of Adeno-associated Virus Type 2 (AAV2) Structural Proteins Suggest a Role in Viral Transcription for AAV Capsids

    PubMed Central

    Aydemir, Fikret; Salganik, Maxim; Resztak, Justyna; Singh, Jasbir; Bennett, Antonette; Agbandje-McKenna, Mavis

    2016-01-01

    ABSTRACT We previously reported that an amino acid substitution, Y704A, near the 2-fold interface of adeno-associated virus (AAV) was defective for transcription of the packaged genome (M. Salganik, F. Aydemir, H. J. Nam, R. McKenna, M. Agbandje-McKenna, and N. Muzyczka, J Virol 88:1071–1079, 2013, doi: http://dx.doi.org/10.1128/JVI.02093-13). In this report, we have characterized the defect in 6 additional capsid mutants located in a region ∼30 Å in diameter on the surface of the AAV type 2 (AAV2) capsid near the 2-fold interface. These mutants, which are highly conserved among primate serotypes, displayed a severe defect (3 to 6 logs) in infectivity. All of the mutants accumulated significant levels of uncoated DNA in the nucleus, but none of the mutants were able to accumulate significant amounts of genomic mRNA postinfection. In addition, wild-type (wt) capsids that were bound to the conformational antibody A20, which is known to bind the capsid surface in the region of the mutants, were also defective for transcription. In all cases, the mutant virus particles, as well as the antibody-bound wild-type capsids, were able to enter the cell, travel to the nucleus, uncoat, and synthesize a second strand but were unable to transcribe their genomes. Taken together, the phenotype of these mutants provides compelling evidence that the AAV capsid plays a role in the transcription of its genome, and the mutants map this functional region on the surface of the capsid near the 2-fold interface. This appears to be the first example of a viral structural protein that is also involved in the transcription of the viral genome that it delivers to the nucleus. IMPORTANCE Many viruses package enzymes within their capsids that assist in expressing their genomes postinfection, e.g., retroviruses. A number of nonenveloped viruses, including AAV, carry proteases that are needed for capsid maturation or for capsid modification during infection. We describe here what appears to

  10. Increased Neural Activation during Picture Encoding and Retrieval in 60-Year-Olds Compared to 20-Year-Olds

    ERIC Educational Resources Information Center

    Burgmans, S.; van Boxtel, M. P. J.; Vuurman, E. F. P. M.; Evers, E. A. T.; Jolles, J.

    2010-01-01

    Brain aging has been associated with both reduced and increased neural activity during task execution. The purpose of the present study was to investigate whether increased neural activation during memory encoding and retrieval is already present at the age of 60 as well as to obtain more insight into the mechanism behind increased activity.…

  11. An Analysis of Mathematics Interventions: Increased Time-on-Task Compared with Computer-Assisted Mathematics Instruction

    ERIC Educational Resources Information Center

    Calhoun, James M., Jr.

    2011-01-01

    Student achievement is not progressing on mathematics as measured by state, national, and international assessments. Much of the research points to mathematics curriculum and instruction as the root cause of student failure to achieve at levels comparable to other nations. Since mathematics is regarded as a gate keeper to many educational…

  12. Increasing Fruit and Vegetable Intake among Children: Comparing Long-Term Effects of a Free Distribution and a Multicomponent Program

    ERIC Educational Resources Information Center

    Reinaerts, E.; Crutzen, R.; Candel, M.; De Vries, N. K.; De Nooijer, J.

    2008-01-01

    The aim of this study was to evaluate and compare the effectiveness of two primary school-based interventions on children's fruit and vegetable (F&V) consumption on the long term (2 years after the start of the interventions). Six primary schools were recruited and randomly assigned to (i) a daily free distribution program for the whole school or…

  13. Increased Sleep Disturbances in Thai Children With Attention-Deficit Hyperactivity Disorder Compared With Typically Developing Children.

    PubMed

    Chiraphadhanakul, Kobrat; Jaimchariyatam, Nattapong; Pruksananonda, Chandhita; Chonchaiya, Weerasak

    2016-01-01

    This study compares sleep disturbances in Thai children aged 5-12 years with attention-deficit hyperactivity disorder (ADHD) and typically developing children using the Children's Sleep Habits Questionnaire (CSHQ)-Thai version. Fifty-five children with ADHD and 110 typically developing children were enrolled. Their parents completed the CSHQ, the ADHD rating scales, and the Strengths and Difficulties Questionnaire (SDQ). Children with ADHD had significantly higher scores in all subscales of the CSHQ compared to controls. Among children with ADHD, children with higher SDQ scores (> 15) appeared to have more sleep disturbances than those with relatively lower SDQ scores. Moreover, fewer sleep-related behavioral problems were observed in the medication treated group, which is particularly new to the field and for some perhaps not unexpected clinically. PMID:26629892

  14. High-Tech or Low-Tech? Comparing Self-Monitoring Systems to Increase Task Independence for Students with Autism

    ERIC Educational Resources Information Center

    Bouck, Emily C.; Savage, Melissa; Meyer, Nancy K.; Taber-Doughty, Teresa; Hunley, Megan

    2014-01-01

    Independence is the ultimate goal for students with disabilities, including secondary students with autism. One avenue targeted for increasing independence and decreasing prompt-dependency is through self-monitoring. In this study, investigators sought to determine whether a difference exists in levels of task independence when three students with…

  15. Wave reflection and central aortic pressure are increased in response to static and dynamic muscle contraction at comparable workloads.

    PubMed

    Edwards, David G; Mastin, Corey R; Kenefick, Robert W

    2008-02-01

    We determined the effects of static and dynamic muscle contraction at equivalent workloads on central aortic pressure and wave reflection. At random, 14 healthy men and women (23 +/- 5 yr of age) performed a static handgrip forearm contraction [90 s at 30% of maximal voluntary contraction (MVC)], dynamic handgrip contractions (1 contraction/s for 180 s at 30% MVC), and a control trial. During static and dynamic trials, tension-time index was controlled by holding peak tension constant. Measurements of brachial artery blood pressure and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were conducted at baseline, during each trial, and during 1 min of postexercise ischemia (PEI). Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. AI increased during both static and dynamic trials (static, 5.2 +/- 3.1 to 11.8 +/- 3.4%; dynamic, 5.8 +/- 3.0 to 13.3 +/- 3.4%; P < 0.05) and further increased during PEI (static, 18.5 +/- 3.1%; dynamic, 18.6 +/- 2.9%; P < 0.05). Peripheral and central systolic and diastolic pressures increased (P < 0.05) during both static and dynamic trials and remained elevated during PEI. AI and pressure responses did not differ between static and dynamic trials. Peripheral and central pressures increased similarly during static and dynamic contraction; however, the rise in central systolic pressure during both conditions was augmented by increased wave reflection. The present data suggest that wave reflection is an important determinant of the central blood pressure response during forearm muscle contractions.

  16. Increasing CO[sub 2]: Comparative responses of the C[sub 4] grass Schizachyrium and grassland invader Prosopis

    SciTech Connect

    Polley, H.W.; Johnson, H.B.; Mayeux, H.S. )

    1994-06-01

    Woody C[sub 3] Prosopis glandulosa (honey mesquite) and C[sub 4] perennial grass Schizachyrium scoparium (little bluestem) were grown along a gradient of daytime carbon dioxide concentrations from near 340 to 200 [mu]mol/mol air in a 38 m long controlled environment chamber. The authors studied the effects of historical and prehistorical increases in atmospheric CO[sub 2] concentration on growth, resource use, and competitive interactions of a species representative of C[sub 4]-dominated grasslands in the SW United States and the invasive legume P. glandulosa. Increasing CO[sub 2] concentration stimulated N[sub 2] fixation by individually grown P. glandulosa and elicited in C[sub 3] seedlings a similar relative increase in leaf intercellular CO[sub 2] concentration, net assimilation rate, and intrinsic water use efficiency (leaf net assimilation rate/stomatal conductance). Aboveground biomass of P. glandulosa was not altered by CO[sub 2] concentration, but belowground biomass and whole-plant water and nitrogen use efficiencies increased linearly with CO[sub 2] concentration in seedlings that were grown alone. Biomass produced by P. glandulosa that was grown with S. scoparium was not affected by CO[sub 2] concentration. Stomatal conductance declined and leaf assimilation rates of S. scoparium at near maximum incident light increased at higher CO[sub 2] concentration, but there was no effect of CO[sub 2] concentration on biomass production or whole-plant water use efficiency of the C[sub 4] grass. Rising CO[sub 2] concentration, especially the 27% increase since the beginning of the 19th century, may have contributed to more abundant P. glandulosa on C[sub 4] grasslands by stimulating the shrub's growth or reducing the amount of resources that the C[sub 3] required. Much of the potential response of P. glandulosa to CO[sub 2] concentration, however, appears to be contingent on the shrub's escaping competition with neighboring grasses. 62 refs., 10 figs., 1 tab.

  17. Increased vital and total lung capacities in Tibetan compared to Han residents of Lhasa (3,658 m).

    PubMed

    Droma, T; McCullough, R G; McCullough, R E; Zhuang, J G; Cymerman, A; Sun, S F; Sutton, J R; Moore, L G

    1991-11-01

    Larger chest dimensions and lung volumes have been reported for Andean high-altitude natives compared with sea-level residents and implicated in raising lung diffusing capacity. Studies conducted in Nepal suggested that lifelong Himalayan residents did not have enlarged chest dimensions. To determine if high-altitude Himalayans (Tibetans) had larger lung volumes than acclimatized newcomers (Han "Chinese"), we studied 38 Tibetan and 43 Han residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m) matched for age, height, weight, and smoking history. The Tibetan compared with the Han subjects had a larger total lung capacity [6.80 +/- 0.19 (mean +/- SEM) vs 6.24 +/- 0.18 l BTPS, P less than 0.05], vital capacity (5.00 +/- 0.08 vs 4.51 +/- 0.10 1 BTPS, P less than 0.05), and tended to have a greater residual volume (1.86 +/- 0.12 vs 1.56 +/- 0.09 1 BTPS, P less than 0.06). Chest circumference was greater in the Tibetan than the Han subjects (85 +/- 1 vs 82 +/- 1 cm, P less than 0.05) and correlated with vital capacity in each group as well as in the two groups combined (r = 0.69, P less than 0.05). Han who had migrated to high altitude as children (less than or equal to 5 years old, n = 6) compared to Han adult migrants (greater than or equal to 18 years old, n = 26) were shorter but had similar lung volumes and capacities when normalized for body size. The Tibetans' vital capacity and total lung capacity in relation to body size were similar to values reported previously for lifelong residents of high altitude in South and North America. Thus, Tibetans, like North and South American high-altitude residents, have larger lung volumes. This may be important for raising lung diffusing capacity and preserving arterial oxygen saturation during exercise.

  18. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel.

    PubMed

    Payne, Christopher D; Li, Ying Grace; Small, David S; Ernest, C Steven; Farid, Nagy A; Jakubowski, Joseph A; Brandt, John T; Salazar, Daniel E; Winters, Kenneth J

    2007-11-01

    Prasugrel pharmacodynamics and pharmacokinetics after a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MD) were compared in a 3-way crossover study to clopidogrel 600-mg/75-mg and 300-mg/75-mg LD/MD in 41 healthy, aspirin-free subjects. Each LD was followed by 7 days of daily MD and a 14-day washout period. Inhibition of platelet aggregation (IPA) was assessed by turbidometric aggregometry (20 and 5 microM ADP). Prasugrel 60-mg achieved higher mean IPA (54%) 30 minutes post-LD than clopidogrel 300-mg (3%) or 600-mg (6%) (P < 0.001) and greater IPA by 1 hour (82%) and 2 hours (91%) than the 6-hour IPA for clopidogrel 300-mg (51%) or 600-mg (69%) (P < 0.01). During MD, IPA for prasugrel 10-mg (78%) exceeded that of clopidogrel (300-mg/75-mg, 56%; 600-mg/75-mg, 52%; P < 0.001). Active metabolite area under the concentration-time curve (AUC0-tlast) after prasugrel 60-mg (594 ng.hr/mL) was 2.2 times that after clopidogrel 600-mg. Prasugrel active metabolite AUC0-tlast was consistent with dose-proportionality from 10-mg to 60-mg, while clopidogrel active metabolite AUC0-tlast exhibited saturable absorption and/or metabolism. In conclusion, greater exposure to prasugrel's active metabolite results in faster onset, higher levels, and less variability of platelet inhibition compared with high-dose clopidogrel in healthy subjects. PMID:18030066

  19. Increased susceptibility to oxidation of vitamin E in mitochondrial fractions compared with synaptosomal fractions from rat brains.

    PubMed

    Vatassery, G T; Smith, W E; Quach, H T

    1994-01-01

    The in vitro oxidation of vitamin E (alpha tocopherol) in rat brain synaptosomes and mitochondria by 2,2'-azo-bis-(2'-amidinopropane) dihydrochloride (ABAPH), a free radical generator, was studied. Subcellular fractions (300 micrograms total protein) were suspended in different buffers at pH 7.4 and incubated at 37 degrees C. In the presence of 0.5 mM ABAPH the mitochondrial alpha tocopherol began to get oxidized after a lag time or induction time of 15 min compared with a lag time of 30 min for the synaptosomal fraction. Thus the reserve of reducing compounds that are responsible for delaying tocopherol oxidation is less in mitochondria than in synaptosomes. More tocopherolquinone was produced during incubations without ABAPH compared with incubations in the presence of ABAPH suggesting that the mechanism of oxidation of tocopherol differs under these two conditions. When mitochondria were incubated in buffer without oxidants the production of tocopherolquinone preceded that of thiobarbituric acid reactive substances, an indicator of peroxidation of fatty acids. Therefore, alpha tocopherol is active as an anti-oxidant in mitochondrial membranes and the production of alpha tocopherolquinone could be a monitor of mild membrane oxidation under in vitro conditions. The ease of oxidation of mitochondrial tocopherol suggests a general vulnerability of the mitochondrial membranes to oxidation. Adding vitamin E or its water soluble analogs during in vitro experiments may improve the stability and viability of mitochondria. Furthermore, antioxidant protection by vitamin E may be crucial for the maintenance of tissues, such as brain, whose function is critically dependent upon the availability of high energy phosphates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8130733

  20. Near-infrared spectroscopy based neurofeedback training increases specific motor imagery related cortical activation compared to sham feedback.

    PubMed

    Kober, S E; Wood, G; Kurzmann, J; Friedrich, E V C; Stangl, M; Wippel, T; Väljamäe, A; Neuper, C

    2014-01-01

    In the present study we implemented a real-time feedback system based on multichannel near-infrared spectroscopy (NIRS). Prior studies indicated that NIRS-based neurofeedback can enhance motor imagery related cortical activation. To specify these prior results and to confirm the efficacy of NIRS-based neurofeedback, we examined changes in blood oxygenation level collected in eight training sessions. One group got real feedback about their own brain activity (N=9) and one group saw a playback of another person's feedback recording (N=8). All participants performed motor imagery of a right hand movement. Real neurofeedback induced specific and focused brain activation over left motor areas. This focal brain activation became even more specific over the eight training sessions. In contrast, sham feedback led to diffuse brain activation patterns over the whole cortex. These findings can be useful when training patients with focal brain lesions to increase activity of specific brain areas for rehabilitation purpose.

  1. Children's Increased Emotional Egocentricity Compared to Adults Is Mediated by Age-Related Differences in Conflict Processing.

    PubMed

    Hoffmann, Ferdinand; Singer, Tania; Steinbeis, Nikolaus

    2015-01-01

    This study investigated the cognitive mechanisms underlying age-related differences in emotional egocentricity bias (EEB) between children (aged 7-12 years, n = 30) and adults (aged 20-30 years, n = 30) using a novel paradigm of visuogustatory stimulation to induce pleasant and unpleasant emotions. Both children and adults showed an EBB, but that of children was larger. The EEB did not correlate with other measures of egocentricity. Crucially, the developmental differences in EEB were mediated by age-related changes in conflict processing and not visual perspective taking, response inhibition, or processing speed. This indicates that different types of egocentricity develop independently of one another and that the increased ability to overcome EEB can be explained by age-related improvements in conflict processing.

  2. Comparative biology and expression of TENP, an egg protein related to the bacterial permeability-increasing family of proteins.

    PubMed

    Whenham, Natasha; Wilson, Peter W; Bain, Maureen M; Stevenson, Lynn; Dunn, Ian C

    2014-03-15

    The 'transiently expressed in neural precursors' (TENP) gene product is a member of the bacterial/permeability-increasing (BPI) family of antimicrobial proteins but was first identified as having a role in an early neurological event occurring in post-mitotic cells. However, recent characterisation of the egg white proteome has shown that TENP is an important egg component constituting ~0.1-0.5% of the total protein and suggesting it is expressed in the adult oviduct. In this study we confirmed quantitatively that the expression of TENP is largely confined to the tubular glands of the magnum of the oviduct, where egg white synthesis occurs, with around 10,000 times more expression than in the embryo where TENP was first identified. TENP expression is significantly increased with the administration of oestrogen or progesterone (P<0.001) and is reduced in regressed oviducts (P<0.001) demonstrating gonadal steroid control, typical of an oviduct and egg specific gene. A putative translational start site for TENP has been characterised and the evidence indicates that it is expressed as one predominant transcript. In comparison with the published sequence, insertion and deletion events have been identified causing a partial frame-shift that results in an altered amino acid sequence to that previously documented. TENP is conserved across divergent avian species being found in chicken, turkey, duck and zebra finch and its expression profile confirmed in both chicken and duck. Similarity searches have shown homology with the BPI-like family of innate immune genes, particularly with palate, lung and nasal epithelial clone (PLUNC) members of this family. We therefore believe that at least in adults the role of TENP is as a major component of egg, particularly the white and it is probable that it contributes to its antimicrobial function.

  3. Local inpatient units may increase patients’ utilization of outpatient services: a comparative cohort-study in Nordland County, Norway

    PubMed Central

    Myklebust, Lars Henrik; Sørgaard, Knut; Wynn, Rolf

    2015-01-01

    Objectives In the last few decades, there has been a restructuring of the psychiatric services in many countries. The complexity of these systems may represent a challenge to patients that suffer from serious psychiatric disorders. We examined whether local integration of inpatient and outpatient services in contrast to centralized institutions strengthened continuity of care. Methods Two different service-systems were compared. Service-utilization over a 4-year period for 690 inpatients was extracted from the patient registries. The results were controlled for demographic variables, model of service-system, central inpatient admission or local inpatient admission, diagnoses, and duration of inpatient stays. Results The majority of inpatients in the area with local integration of inpatient and outpatient services used both types of care. In the area that did not have beds locally, many patients that had been hospitalized did not receive outpatient follow-up. Predictors of inpatients’ use of outpatient psychiatric care were: Model of service-system (centralized vs decentralized), a diagnosis of affective disorder, central inpatient admission only, and duration of inpatient stays. Conclusion Psychiatric centers with local inpatient units may positively affect continuity of care for patients with severe psychiatric disorders, probably because of a high functional integration of inpatient and outpatient care. PMID:26604843

  4. Neuronal Populations in the Basolateral Nuclei of the Amygdala Are Differentially Increased in Humans Compared With Apes: A Stereological Study

    PubMed Central

    Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M.; Sherwood, Chet C.; Annese, Jacopo; Allman, John M.; Buckwalter, Joseph A.; Hof, Patrick R.; Semendeferi, Katerina

    2016-01-01

    In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. PMID:22473387

  5. Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules.

    PubMed

    Egert, Sarah; Wolffram, Siegfried; Schulze, Beate; Langguth, Peter; Hubbermann, Eva Maria; Schwarz, Karin; Adolphi, Berit; Bosy-Westphal, Anja; Rimbach, Gerald; Müller, Manfred James

    2012-02-01

    The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22-28 years took a single oral dose of approximately 130 mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3 % quercetin aglycone plus 6·7 % quercetin-4'-glucoside) or quercetin powder-filled hard capsules (100 % quercetin aglycone). Blood samples were drawn before and after quercetin administration over a 24 h period. The concentrations of quercetin and its monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin) and tamarixetin (4'-O-methyl quercetin), were measured by HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability as determined by comparing the plasma concentration-time curves of quercetin was found to be five times and the cmax values six times higher after ingestion of 130 mg quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In contrast, tmax did not differ significantly between the two treatments. The cmax values for isorhamnetin and tamarixetin were four and nine times higher after ingestion of quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In conclusion, quercetin from quercetin-enriched cereal bars is significantly more bioavailable than from quercetin powder-filled hard capsules. PMID:21774840

  6. Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity.

    PubMed

    Mendanha, Sebastião A; Moura, Soraia S; Anjos, Jorge L V; Valadares, Marize C; Alonso, Antonio

    2013-02-01

    Terpenes are considered potent skin permeation enhancers with low toxicity. Electron paramagnetic resonance (EPR) spectroscopy of the spin label 5-doxyl stearic acid (5-DSA) was used to monitor the effect of sesquiterpene nerolidol and various monoterpenes on membrane fluidity in erythrocyte and fibroblast cells. In addition, the hemolytic levels and cytotoxic effects on cultured fibroblast cells were also measured to investigate possible relationships between the cellular irritation potentials of terpenes and the ability to modify membrane fluidity. All terpenes increased cell membrane fluidity with no significant differences between the monoterpenes, but the effect of sesquiterpene was significantly greater than that of the monoterpenes. The IC(50) values for the terpenes in the cytotoxicity assay indicated that 1,8-cineole showed lower cytotoxicity and α-terpineol and nerolidol showed higher cytotoxicity. The correlation between the hemolytic effect and the IC(50) values for fibroblast viability was low (R=0.61); however, in both tests, nerolidol was among the most aggressive of terpenes and 1,8-cineole was among the least aggressive. Obtaining information concerning the toxicity and potency of terpenes could aid in the design of topical formulations optimized to facilitate drug absorption for the treatment of many skin diseases.

  7. Increased muscular volume and cuticular specialisations enhance jump velocity in solitarious compared with gregarious desert locusts, Schistocerca gregaria.

    PubMed

    Rogers, Stephen M; Riley, Joanna; Brighton, Caroline; Sutton, Gregory P; Cullen, Darron A; Burrows, Malcolm

    2016-03-01

    The desert locust, Schistocerca gregaria, shows a strong phenotypic plasticity. It can develop, depending upon population density, into either a solitarious or gregarious phase that differs in many aspects of behaviour, physiology and morphology. Prominent amongst these differences is that solitarious locusts have proportionately longer hind femora than gregarious locusts. The hind femora contain the muscles and energy-storing cuticular structures that propel powerful jumps using a catapult-like mechanism. We show that solitarious locusts jump on average 23% faster and 27% further than gregarious locusts, and attribute this improved performance to three sources: first, a 17.5% increase in the relative volume of their hind femur, and hence muscle volume; second, a 24.3% decrease in the stiffness of the energy-storing semi-lunar processes of the distal femur; and third, a 4.5% decrease in the stiffness of the tendon of the extensor tibiae muscle. These differences mean that solitarious locusts can generate more power and store more energy in preparation for a jump than can gregarious locusts. This improved performance comes at a cost: solitarious locusts expend nearly twice the energy of gregarious locusts during a single jump and the muscular co-contraction that energises the cuticular springs takes twice as long. There is thus a trade-off between achieving maximum jump velocity in the solitarious phase against the ability to engage jumping rapidly and repeatedly in the gregarious phase. PMID:26936638

  8. Increased muscular volume and cuticular specialisations enhance jump velocity in solitarious compared with gregarious desert locusts, Schistocerca gregaria.

    PubMed

    Rogers, Stephen M; Riley, Joanna; Brighton, Caroline; Sutton, Gregory P; Cullen, Darron A; Burrows, Malcolm

    2016-03-01

    The desert locust, Schistocerca gregaria, shows a strong phenotypic plasticity. It can develop, depending upon population density, into either a solitarious or gregarious phase that differs in many aspects of behaviour, physiology and morphology. Prominent amongst these differences is that solitarious locusts have proportionately longer hind femora than gregarious locusts. The hind femora contain the muscles and energy-storing cuticular structures that propel powerful jumps using a catapult-like mechanism. We show that solitarious locusts jump on average 23% faster and 27% further than gregarious locusts, and attribute this improved performance to three sources: first, a 17.5% increase in the relative volume of their hind femur, and hence muscle volume; second, a 24.3% decrease in the stiffness of the energy-storing semi-lunar processes of the distal femur; and third, a 4.5% decrease in the stiffness of the tendon of the extensor tibiae muscle. These differences mean that solitarious locusts can generate more power and store more energy in preparation for a jump than can gregarious locusts. This improved performance comes at a cost: solitarious locusts expend nearly twice the energy of gregarious locusts during a single jump and the muscular co-contraction that energises the cuticular springs takes twice as long. There is thus a trade-off between achieving maximum jump velocity in the solitarious phase against the ability to engage jumping rapidly and repeatedly in the gregarious phase.

  9. Infections Are Not Increased in Scleroderma Compared to Non-Inflammatory Musculoskeletal Disorders Prior to Disease Onset

    PubMed Central

    Pope, Janet E; Goodwin, Jodi L; Ouimet, Janine M; Krizova, Adriana; Laskin, Matthew

    2007-01-01

    The etiology of scleroderma (SSc) is unknown; immunogenic stimuli such as infections and vaccinations could theoretically be risk factors for scleroderma. Our objective was to assess the relationship between viral and bacterial infec-tions, and vaccinations, prior to diagnosis of SSc compared to non-inflammatory controls. Methods: A questionnaire was sent to individuals with SSc (n =83) and controls (n=351) with non-inflammatory musculoskeletal (MSK) disorders (os-teoarthritis, n = 204; tendonitis, n = 58; fibromyalgia, n= 89) from a rheumatology practice. Questions ascertained past in-fections, exposure to infectious agents and vaccination history. Results: The response rate was 78% (SSc) and 56% (MSK controls). The mean age was 56 ± 1.6 (SSc) and 58 ± 0.9 (MSK); 88% (SSc) and 82% (MSK) were female. No association between prior infections and SSc was observed. In fact, controls were more likely than SSc subjects to report any infec-tion within 1-year prior to disease diagnosis (35% vs. 16%, p<0.006), or to have suffered a trauma to affected joints prior to diagnosis (44% vs. 19%, p<0.0002). Within the 1-year prior to disease diagnosis, controls reported slightly more strep-tococcal infections (p<0.2), infections with diarrhea and vomiting (p<0.3), and antibiotic use (p<0.09), although none of these results were statistically significant. Histories of any hepatitis, rubella, any bacterial infection, and having had a pre-vious positive tuberculosis skin test were not significantly different between groups and were actually more often reported by the control subjects. SSc reported slightly more hepatitis B (p<0.08), more rheumatic fever (p<0.8) in past, and herpes zoster (p<0.4), although no differences reached significance. Conclusion: This study does not support that self-report of symptomatic infections are more likely to occur ever (prior to diagnosis) or within 1-year prior to symptom onset of SSc, or that vaccinations in adulthood trigger SSc. PMID:19088895

  10. A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

    PubMed Central

    Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

    2012-01-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

  11. Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates.

    PubMed

    Fishbourne, Emma; Hutet, Evelyne; Abrams, Charles; Cariolet, Roland; Le Potier, Marie-Frédérique; Takamatsu, Haru-H; Dixon, Linda K

    2013-10-01

    Modulation of the expression of chemokines and chemokine receptors in whole blood was compared following infection of pigs with high and low virulence isolates of African swine fever virus. Levels of mRNAs for CCL2, CCL3L1, CCL4, CXCL10, CCR1 and CCR5 were significantly increased in at least one time point following infection in two experiments and CCL5, CCR9 and CXCR4 mRNA were significantly increased in one of the experiments. The results showed that greatest fold increases in mRNAs for CXCL10 and CCL2 were observed following infection of pigs. CXCL10 mRNA was increased by up to 15 fold in infected compared to uninfected pigs. CXCL10 protein was also detected in serum from pigs infected with the high virulence Benin 97/1 isolate. Levels of CCL2 mRNA were increased in pigs infected with high virulence Benin 97/1 isolate compared to low virulence OURT88/3 isolate and this correlated with an increase of greater than 30 fold in levels of CCL2 protein detected in serum from pigs infected with this isolate. An increase in overall chemotaxis active compounds in defibrinated plasma samples from Benin 97/1 infected pigs was observed at 3 days post-infection (dpi) and a decrease by 7 dpi as measured by chemotaxis assay using normal pig leucocytes in vitro. Increased levels of CXCL10 may either contribute to the activation of lymphocyte priming toward the Th1 phenotype or induction of T lymphocyte apoptosis. Increased levels of CCL2, a chemoattractant for macrophages, may result in increased recruitment of monocytes from bone marrow thus increasing the pool of cells susceptible to infection.

  12. Modification of antisense phosphodiester oligodeoxynucleotides by a 5' cholesteryl moiety increases cellular association and improves efficacy.

    PubMed Central

    Krieg, A M; Tonkinson, J; Matson, S; Zhao, Q; Saxon, M; Zhang, L M; Bhanja, U; Yakubov, L; Stein, C A

    1993-01-01

    Phosphodiester oligodeoxynucleotides bearing a 5' cholesteryl (chol) modification bind to low density lipoprotein (LDL), apparently by partitioning the chol-modified oligonucleotides into the lipid layer. Both HL60 cells and primary mouse spleen T and B cells incubated with fluorescently labeled chol-modified oligonucleotide showed substantially increased cellular association by flow cytometry and increased internalization by confocal microscopy compared to an identical molecule not bearing the chol group. Cellular internalization of chol-modified oligonucleotide occurred at least partially through the LDL receptor; it was increased in mouse spleen cells by cell culture in lipoprotein-deficient medium and/or lovastatin, and it was decreased by culture in high serum medium. To determine whether chol-modified oligonucleotides are more potent antisense agents, we titered antisense unmodified phosphodiester and chol-modified oligonucleotides targeted against a mouse immunosuppressive protein. Murine spleen cells cultured with 20 microM phosphodiester antisense oligonucleotides had a 2-fold increase in RNA synthesis, indicating the expected lymphocyte activation. Antisense chol-modified oligonucleotides showed an 8-fold increase in relative potency: they caused a 2-fold increase in RNA synthesis at just 2.5 microM. The increased efficacy was blocked by heparin and was further increased by cell culture in 1% (vs. 10%) fetal bovine serum, suggesting that the effect may, at least in part, be mediated via the LDL receptor. Antisense chol-modified oligonucleotides are sequence specific and have increased potency as compared to unmodified oligonucleotides. Images PMID:8430072

  13. Comparing the impact of increasing condom use or HIV pre-exposure prophylaxis (PrEP) use among female sex workers.

    PubMed

    Mukandavire, Zindoga; Mitchell, Kate M; Vickerman, Peter

    2016-03-01

    In many settings, interventions targeting female sex workers (FSWs) could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP) could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use-one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed 'pimps') was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used.

  14. Keratinocyte growth factor in inflammatory bowel disease. Increased mRNA transcripts in ulcerative colitis compared with Crohn's disease in biopsies and isolated mucosal myofibroblasts.

    PubMed Central

    Bajaj-Elliott, M.; Breese, E.; Poulsom, R.; Fairclough, P. D.; MacDonald, T. T.

    1997-01-01

    Inflammation in the gastrointestinal tract is associated with increased epithelial cell proliferation. Keratinocyte growth factor (KGF) is an epithelial cell mitogen widely expressed by mesenchymal cells subjacent to the epithelial cells. In this study, we have investigated the expression and distribution of KGF in normal and diseased (Crohn's disease and ulcerative colitis(UC)) intestine by quantitative competitive reverse-transcriptase polymerase chain reaction in whole biopsies and purified lamina propria myofibroblasts and by in situ hybridization. Analysis of whole mucosal biopsies reveals significantly higher numbers of KGF mRNA transcripts in UC compared with Crohn's colitis and control colon (P < 0.001). KGF transcripts were also elevated in Crohn's ileitis compared with normal ileum. In situ hybridization showed a marked increase in cells expressing KGF mRNA throughout the lamina propria in both UC and Crohn's tissue. In Crohn's disease, positively hybridizing cells were only rarely seen in the submucosa but were abundant around the bases of the crypts and were not associated with lymphoid aggregates. In purified mucosal myofibroblasts, increased (15- to 20-fold) KGF mRNA expression was seen in UC compared with control and Crohn's tissue. These results confirm and extend earlier studies showing that KGF transcripts are elevated in inflammatory bowel disease, but they show for the first time that transcripts are higher in UC than Crohn's disease because of increased production by mucosal mesenchymal cells. Images Figure 2 Figure 3 PMID:9358773

  15. The Effect of Omega-3 Docosahexaenoic Acid Supplementation on Gestational Length: Randomized Trial of Supplementation Compared to Nutrition Education for Increasing n-3 Intake from Foods

    PubMed Central

    Harris, Mary A.; Reece, Melanie S.; McGregor, James A.; Wilson, John W.; Burke, Shannon M.; Wheeler, Marsha; Anderson, Jennifer E.; Auld, Garry W.; French, Janice I.; Allen, Kenneth G. D.

    2015-01-01

    Objective. DHA supplementation was compared to nutrition education to increase DHA consumption from fish and DHA fortified foods. Design. This two-part intervention included a randomized double-blind placebo controlled DHA supplementation arm and a nutrition education arm designed to increase intake of DHA from dietary sources by 300 mg per day. Setting. Denver Health Hospitals and Clinics, Denver, Colorado, USA. Population. 871 pregnant women aged 18–40 were recruited between16 and 20 weeks of gestation of whom 564 completed the study and complete delivery data was available in 505 women and infants. Methods. Subjects received either 300 or 600 mg DHA or olive oil placebo or nutrition education. Main Outcome Variable. Gestational length. Results. Gestational length was significantly increased by 4.0–4.5 days in women supplemented with 600 mg DHA per day or provided with nutrition education. Each 1% increase in RBC DHA at delivery was associated with a 1.6-day increase in gestational length. No significant effects on birth weight, birth length, or head circumference were demonstrated. The rate of early preterm birth (1.7%) in those supplemented with DHA (combined 300 and 600 mg/day) was significantly lower than in controls. Conclusion. Nutrition education or supplementation with DHA can be effective in increasing gestational length. PMID:26413500

  16. Increased expression of the sodium transporter BSC-1 in spontaneously hypertensive rats.

    PubMed

    Sonalker, Prajakta A; Tofovic, Stevan P; Jackson, Edwin K

    2004-12-01

    The purpose of this study was to compare the expression of BSC-1 (bumetanide-sensitive Na+-K+-2Cl- cotransporter) in kidneys of spontaneously hypertensive rats (SHR) versus Wistar-Kyoto (WKY) rats by immunoblotting and reverse transcription-polymerase chain reaction. To determine the specificity of any observed changes in BSC-1 expression, we also compared expression of the thiazide sensitive Na+-Cl- cotransporter (TSC), the type-3 Na+-H+ exchanger (NHE-3), Na+-K+-ATPase-alpha1, the inwardly rectifying K+ channel (ROMK-1), the type-1 Na+-HCO3- cotransporter (NBC-1), aquaporin-1, and aquaporin-2. Analyses were performed on outer cortex, outer medulla, and inner medulla. BSC-1 protein was detected in outer medulla and was markedly (6-fold) higher in SHR. TSC protein was detected in the cortex and was not overexpressed in SHR. Aquaporin-1 protein was detected in all three regions and was not overexpressed in SHR. Aquaporin-2 and ROMK-1 proteins were detected in all three regions, but were moderately elevated (2-fold) only in the SHR inner medulla. Na+-K+-ATPase and NHE-3 proteins were detected in all three regions. Na+-K+-ATPase-alpha1 was modestly (25%) increased in SHR outer and inner medulla, whereas NHE-3 was moderately (2-fold) increased in the SHR cortex and inner medulla. NBC-1 protein was detected only in the cortex and was higher (2-fold) in SHR. mRNA levels of BSC-1, aquaporin-2, and ROMK-1 were not elevated in SHR, indicating a post-translational mechanism of protein overexpression. High-dose furosemide increased fractional sodium excretion more in SHR than WKY (3-fold). We conclude that increased expression of BSC-1, and to a lesser extent, aquaporin-2, ROMK-1, NHE-3, and NBC-1 may contribute to the pathogenesis of hypertension in the SHR.

  17. Increasing of Food and Bioenergy Potato Resources by Microbial Influence on Tubers Phytohormonal Status

    NASA Astrophysics Data System (ADS)

    Kiprushkina, Elena I.; Baranenko, Denis A.

    2014-12-01

    Potato and its by-products became a promising both food and bioenergy resource. The determination of the bacteriaantagonists influence on phytohormone status and productivity of potato tubers was studied. The indole-3-acetic acid content during the dormancy end and germinating in the tubers treated with Bacillus subtilis Ch-13 was fewer than in the control samples. L-tryptophan significant quantity compared to the control was found in the treated tubers in a state of physiological dormancy (more than 2-fold) and especially during active germination (43 times greater). Average potato yield increase at treated fields was of 18.8 %.

  18. Compared with stearic acid, palmitic acid increased the yield of milk fat and improved feed efficiency across production level of cows.

    PubMed

    Rico, J E; Allen, M S; Lock, A L

    2014-02-01

    The effects of dietary palmitic and stearic acids on feed intake, yields of milk and milk components, and feed efficiency of dairy cows were evaluated in an experiment with a crossover arrangement of treatments with a covariate period. Cows with a wide range of milk production (38 to 65 kg/d) were used to determine if response to fat supplementation varied according to production level. Thirty-two Holstein cows (143 ± 61 d in milk) were assigned randomly to a treatment sequence within level of milk production. Treatments were diets supplemented (2% of diet dry matter) with palmitic acid (PA; 97.9% C16:0) or stearic acid (SA; 97.4% C18:0). Treatment periods were 21 d and cows were fed a nonfat supplemented diet for 14 d immediately before the first treatment period. The final 4d of each period were used for sample and data collection. Milk production measured during the covariate period (preliminary milk yield) was used as the covariate. No interactions were detected between treatment and preliminary milk yield for the production response variables measured. Compared with SA, the PA treatment increased milk fat concentration (3.66 vs. 3.55%) and yield (1.68 vs. 1.59 kg/d), and 3.5% fat-corrected milk yield (47.5 vs. 45.6 kg/d). Treatment did not affect dry matter intake, milk yield, milk protein yield, body weight, or body condition score. Milk protein concentration was lower for PA compared with SA treatment (3.24 vs. 3.29%). The PA treatment increased feed efficiency (3.5% fat-corrected milk yield/dry matter intake) compared with SA (1.48 vs. 1.40). The increase in milk fat yield by PA was entirely accounted for by a 24% increase in 16-carbon fatty acid output into milk. Yields of de novo (3.2%) and preformed fatty acids (2.9%) were only slightly decreased by PA relative to SA. The PA treatment increased plasma concentration of nonesterified fatty acids (96.3 vs. 88.2 μEq/L) and glucose (56.6 vs. 55.7 mg/dL) compared with SA, but insulin and

  19. Repetition counts: repeated exposure increases intake of a novel vegetable in UK pre-school children compared to flavour-flavour and flavour-nutrient learning.

    PubMed

    Caton, Samantha J; Ahern, Sara M; Remy, Eloise; Nicklaus, Sophie; Blundell, Pam; Hetherington, Marion M

    2013-06-01

    Children are not consuming sufficient amounts of fruits and vegetables in their habitual diet. Methods derived from associative learning theories could be effective at promoting vegetable intake in pre-school children. The objective of the present study was to compare the effectiveness of different learning strategies in promoting the intake of a novel vegetable. Children aged between 9 and 38 months were recruited from UK nurseries. The children (n 72) were randomly assigned to one of three conditions (repeated exposure, flavour-flavour learning or flavour-nutrient learning). Each child was offered ten exposures to their respective version of a novel vegetable (artichoke). Pre- and post-intervention measures of artichoke purée and carrot purée (control vegetable) intake were taken. At pre-intervention, carrot intake was significantly higher than artichoke intake (P<0·05). Intake of both vegetables increased over time (P<0·001); however, when changes in intake were investigated, artichoke intake increased significantly more than carrot intake (P<0·001). Artichoke intake increased to the same extent in all three conditions, and this effect was persistent up to 5 weeks post-intervention. Five exposures were sufficient to increase intake compared to the first exposure (P<0·001). Repeated exposure to three variants of a novel vegetable was sufficient to increase intake of this vegetable, regardless of the addition of a familiar taste or energy. Repetition is therefore a critical factor for promoting novel vegetable intake in pre-school children. PMID:23110783

  20. Increasing metabolic stability via the deuterium kinetic isotope effect: An example from a proline-amide-urea aminothiazole series of phosphatidylinositol-3 kinase alpha inhibitors.

    PubMed

    Fairhurst, Robin A; Caravatti, Giorgio; Guagnano, Vito; Aichholz, Reiner; Blanz, Joachim; Blasco, Francesca; Wipfli, Peter; Fritsch, Christine; Maira, Sauveur-Michel; Schnell, Christian; Seiler, Frank H

    2016-10-01

    In vitro metabolic identification studies with a PI3K-α inhibitor lead molecule 1 identified a single predominant site of oxidative metabolism to be occurring within a tert.butyl moiety. Modification of the tert.butyl group within the lead molecule 1, to the corresponding d9-tert.butyl analogue 2, led to an increase in both the in vitro and in vivo metabolic stability. This increase in metabolic stability resulted in a 2-fold increase in the oral bioavailability measured in the rat, and a 3-fold increase in potency in a chronic in vivo study in the mouse, for 2 when compared to 1.

  1. Increasing metabolic stability via the deuterium kinetic isotope effect: An example from a proline-amide-urea aminothiazole series of phosphatidylinositol-3 kinase alpha inhibitors.

    PubMed

    Fairhurst, Robin A; Caravatti, Giorgio; Guagnano, Vito; Aichholz, Reiner; Blanz, Joachim; Blasco, Francesca; Wipfli, Peter; Fritsch, Christine; Maira, Sauveur-Michel; Schnell, Christian; Seiler, Frank H

    2016-10-01

    In vitro metabolic identification studies with a PI3K-α inhibitor lead molecule 1 identified a single predominant site of oxidative metabolism to be occurring within a tert.butyl moiety. Modification of the tert.butyl group within the lead molecule 1, to the corresponding d9-tert.butyl analogue 2, led to an increase in both the in vitro and in vivo metabolic stability. This increase in metabolic stability resulted in a 2-fold increase in the oral bioavailability measured in the rat, and a 3-fold increase in potency in a chronic in vivo study in the mouse, for 2 when compared to 1. PMID:27575470

  2. Analysis of syncytial nuclear aggregates in preeclampsia shows increased sectioning artefacts and decreased inter-villous bridges compared to healthy placentas.

    PubMed

    Calvert, S J; Jones, C J P; Sibley, C P; Aplin, J D; Heazell, A E P

    2013-12-01

    Syncytial nuclear aggregates (SNAs) are increased in pregnancy complications and include 'true' syncytial knots and inter-villous bridges. Apparent nuclear overlay caused by sectioning artefacts are frequently counted from single sections. Haematoxylin and eosin stained serial sections were assessed for frequency of SNA subtypes in placentas from normal, preeclamptic and fetal growth restricted (FGR) pregnancies. There were more sectioning artefacts and syncytial knots and fewer bridges in samples from preeclampsia compared to controls. There were no significant differences between FGR and control samples. This suggests the villous tree in preeclampsia has less inherent structural support and trophoblast cell dynamics are different.

  3. Transcriptomic analysis of Clostridium thermocellum Populus hydrolysate-tolerant mutant strain shows increased cellular efficiency in response to Populus hydrolysate compared to the wild type strain

    PubMed Central

    2014-01-01

    Background The thermophilic, anaerobic bacterium, Clostridium thermocellum is a model organism for consolidated processing due to its efficient fermentation of cellulose. Constituents of dilute acid pretreatment hydrolysate are known to inhibit C. thermocellum and other microorganisms. To evaluate the biological impact of this type of hydrolysate, a transcriptomic analysis of growth in hydrolysate-containing medium was conducted on 17.5% v/v Populus hydrolysate-tolerant mutant (PM) and wild type (WT) strains of C. thermocellum. Results In two levels of Populus hydrolysate medium (0% and 10% v/v), the PM showed both gene specific increases and decreases of gene expression compared to the wild-type strain. The PM had increased expression of genes in energy production and conversion, and amino acid transport and metabolism in both standard and 10% v/v Populus hydrolysate media. In particular, expression of the histidine metabolism increased up to 100 fold. In contrast, the PM decreased gene expression in cell division and sporulation (standard medium only), cell defense mechanisms, cell envelope, cell motility, and cellulosome in both media. The PM downregulated inorganic ion transport and metabolism in standard medium but upregulated it in the hydrolysate media when compared to the WT. The WT differentially expressed 1072 genes in response to the hydrolysate medium which included increased transcription of cell defense mechanisms, cell motility, and cellulosome, and decreased expression in cell envelope, amino acid transport and metabolism, inorganic ion transport and metabolism, and lipid metabolism, while the PM only differentially expressed 92 genes. The PM tolerates up to 17.5% v/v Populus hydrolysate and growth in it elicited 489 genes with differential expression, which included increased expression in energy production and conversion, cellulosome production, and inorganic ion transport and metabolism and decreased expression in transcription and cell

  4. d-Dimer Levels are Significantly Increased in Blood Taken From Varicose Veins Compared With Antecubital Blood From the Same Patient.

    PubMed

    Lattimer, Christopher R; Kalodiki, Evi; Geroulakos, George; Syed, Daneyal; Hoppensteadt, Debra; Fareed, Jawed

    2015-10-01

    d-Dimer is a prothrombotic biomarker and a very sensitive measure of endogenous fibrinolysis. It is used as a screening test for suspected deep vein thrombosis. This study investigated whether d-dimer levels were increased in the varicose veins of patients in comparison to their own arm samples. Patients, n = 24, 17 male, age 45 (25-91), C2-6, awaiting saphenous laser ablation were compared to matched controls, n = 24, 17 male, age 42 (24-89). Concurrent venous blood samples were taken from the arm and a lower calf/ankle (varicose) vein. The median (interquartile range) d-dimer (ng/mL) level was significantly greater in the ankle than in the arm blood of the same patient at 319 (164-631) versus 281 (167-562), P = .003, Wilcoxon. This did not occur in the controls at 269 (80-564) versus 262 (106-526), P = .361, Wilcoxon. The results indicate increased endogenous fibrinolysis in varicose veins compared with arm blood. This suggests there is more thrombotic activity or dissolution of formed subclinical fibrin thrombus which may explain the association of varicose veins with superficial vein thrombosis. This contrasts with earlier studies reporting a local reduction in fibrinolysis in venous disease.

  5. Increased inflammation and decreased insulin sensitivity indicate metabolic disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros bicornis).

    PubMed

    Schook, Mandi W; Wildt, David E; Raghanti, Mary Ann; Wolfe, Barbara A; Dennis, Patricia M

    2015-01-01

    Black rhinoceros (rhinos) living in zoos express a host of unusual disease syndromes that are associated with increased morbidity and mortality, including hemolytic anemia, rhabdomyolysis, hepatopathy and ulcerative skin disease, hypophosphatemia and iron overload. We hypothesized that iron overload is a consequence and indicator of disturbances related to inflammation and insulin/glucose metabolism. The objectives of this study were to: (1) generate the first baseline information on biomarkers of inflammation (tumor necrosis factor alpha [TNFα], serum amyloid A [SAA]), insulin sensitivity (insulin, glucose and proxy calculations of insulin sensitivity), phosphate and iron stores (ferritin) using banked serum from free-ranging black rhinos; and (2) then compare serum biomarkers between zoo-managed (n=86 individuals) and free-ranging (n=120) animals. Enzyme immunoassays were validated for serum and then biomarker levels analyzed using mixed models while controlling for sex, age and year of sample collection. Concentrations of TNFα, SAA, insulin and insulin-to glucose ratio were higher (P<0.05) in black rhinos managed in ex situ conditions compared to free-living counterparts. Findings indicate that the captive environment is contributing to increased inflammation and decreased insulin sensitivity in this endangered species.

  6. Instant Oatmeal Increases Satiety and Reduces Energy Intake Compared to a Ready-to-Eat Oat-Based Breakfast Cereal: A Randomized Crossover Trial

    PubMed Central

    Rebello, Candida J.; Johnson, William D.; Martin, Corby K.; Han, Hongmei; Chu, Yi-Fang; Bordenave, Nicolas; van Klinken, B. Jan Willem; O'Shea, Marianne; Greenway, Frank L.

    2016-01-01

    Background: Foods that enhance satiety can help consumers to resist environmental cues to eat and help adherence to calorie restriction. The objective of this study was to compare the effect of 2 oat-based breakfast cereals on appetite, satiety, and food intake. Methods: Forty-eight healthy individuals, 18 years of age or older, were enrolled in a randomized, crossover trial. Subjects consumed isocaloric servings of either oatmeal or an oat-based ready-to-eat breakfast cereal (RTEC) in random order at least a week apart. Visual analogue scales measuring appetite and satiety were completed before breakfast and throughout the morning. Lunch was served 4 hours after breakfast. The physicochemical properties of oat soluble fiber (β-glucan) were determined. Appetite and satiety responses were analyzed by area under the curve. Food intake and β-glucan properties were analyzed using t tests. Results: Oatmeal increased fullness (p = 0.001) and reduced hunger (p = 0.005), desire to eat (p = 0.001), and prospective intake (p = 0.006) more than the RTEC. Energy intake at lunch was lower after eating oatmeal compared to the RTEC (p = 0.012). Oatmeal had higher viscosity (p = 0.03), β-glucan content, molecular weight (p < 0.001), and radius of gyration (p < 0.001) than the RTEC. Conclusions: Oatmeal suppresses appetite, increases satiety, and reduces energy intake compared to the RTEC. The physicochemical properties of β-glucan and sufficient hydration of oats are important factors affecting satiety and subsequent energy intake. PMID:26273900

  7. Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content.

    PubMed

    Bach Kristensen, Mette; Hels, Ole; Morberg, Catrine; Marving, Jens; Bügel, Susanne; Tetens, Inge

    2005-07-01

    Meat increases absorption of non-haem iron in single-meal studies. The aim of the present study was to investigate, over a 5 d period, the potential increasing effect of consumption of pork meat in a whole diet on the fractional absorption of non-haem iron and the total absorption of iron, when compared to a vegetarian diet. A randomised cross-over design with 3 x 5 d whole-diet periods with diets containing Danish-produced meat, Polish-produced meat or a vegetarian diet was conducted. Nineteen healthy female subjects completed the study. All main meals in the meat diets contained 60 g of pork meat and all diets had high phytic acid content (1250 mumol/d). All main meals were extrinsically labelled with the radioactive isotope (59)Fe and absorption of iron was measured in a whole body counter. The non-haem iron absorption from the Danish meat diet was significantly higher compared to the vegetarian diet (P=0.031). The mean fractional absorption of non-haem iron was 7.9 (se1.1), 6.8 (se 1.0) and 5.3 (se 0.6) % for the Danish and Polish meat diets and vegetarian diet, respectively. Total absorption of iron was higher for both meat diets compared to the vegetarian diet (Danish meat diet: P=0.006, Polish meat diet: P=0.003). The absorption ratios of the present study were well in accordance with absorption ratios estimated using algorithms on iron bioavailability. Neither the meat diets nor the vegetarian diets fulfilled the estimated daily requirements of absorbed iron in spite of a meat intake of 180 g/d in the meat diets.

  8. Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).

    PubMed

    Nicholls, Stephen J; Brandrup-Wognsen, Gunnar; Palmer, Mike; Barter, Philip J

    2010-01-01

    Statins are the most commonly prescribed agents for lowering levels of low-density lipoprotein (LDL) cholesterol. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statins, the impact of increasing dose has not been fully elucidated. An individual patient data pooled analysis was performed of 32,258 patients in studies comparing the efficacy of rosuvastatin with that of atorvastatin or simvastatin. The impact of increasing dose on lowering LDL cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B was investigated. Doubling the dose of each statin was accompanied by a 4% to 7% greater degree of lowering of all atherogenic lipids. A stronger correlation was observed between changes in LDL cholesterol and non-HDL cholesterol (r = 0.92, p <0.001) or apolipoprotein B (r = 0.76, p <0.001) than triglycerides (r = 0.14, p <0.001). On multivariate analysis, baseline lipid level (p <0.0001) and increasing statin dose (p <0.0001) were strong predictors of achieving treatment goals in high-risk patients. Increasing age was a strong independent predictor of achieving goal for all atherogenic lipids (p <0.0001). Achieving LDL cholesterol goals was also more likely in women (p <0.0001), patients with diabetes (p <0.0001), and patients without atherosclerotic disease (p = 0.0002). In contrast, normal triglyceride levels were more often observed in men (p <0.0001) and patients without diabetes mellitus (p = 0.03). In conclusion, doubling statin dose was associated with greater lowering of LDL cholesterol by 4% to 6% and non-HDL cholesterol by 3% to 6%. Greater lipid goal achievement with increasing dose supports the use of high-dose statin therapy for more effective cardiovascular prevention.

  9. Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers

    PubMed Central

    2013-01-01

    Background Clinical studies have shown that radiotherapy increases the risk of cardiovascular disease at irradiated sites years after exposure. However, there is a lack of biological explanations in humans. We therefore examined human blood vessels exposed to radiotherapy and studied C-reactive protein (CRP) and pentraxin 3 (PTX3), a new marker for adverse cardiovascular outcome dependent on TNF- alpha (TNFα) or interleukin-1beta (IL-1β) expression. Methods Pairs of irradiated and non-irradiated human conduit arteries and veins were harvested from the same patient during autologous free tissue transfer for cancer-reconstruction at a median time of 48 weeks after radiotherapy. Differential gene expression was studied using qRT-PCR, confirmed by immunohistochemistry and cellular origins determined by immunofluorescence. Results Gene expression in irradiated arteries compared to non-irradiated showed a consistent up-regulation of PTX3 in all patients and in a majority of veins (p < 0.001). Both TNFα and IL-1β were increased in irradiated compared to non-irradiated arteries (p < 0.01) and IL-1β correlated to the PTX3 expression (p = 0.017). Immunohistochemical and immunofluorescence staining confirmed an increased expression of PTX3 in endothelial cells, macrophages and smooth muscle cells. Conclusions The sustained expression of PTX3 in arteries and veins tie biological evidence in humans to clinical studies and encourage further exploration of innate immunity in the pathogenesis of a radiation-induced vasculopathy. PMID:24060373

  10. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.

    PubMed

    Main, Penelope A E; Thomas, Philip; Esterman, Adrian; Fenech, Michael F

    2013-07-01

    Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally

  11. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress

    PubMed Central

    Fenech, Michael F.

    2013-01-01

    Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case–sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally

  12. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.

    PubMed

    Main, Penelope A E; Thomas, Philip; Esterman, Adrian; Fenech, Michael F

    2013-07-01

    Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally

  13. Increased Genomic Integrity of an Improved Protein-Based Mouse Induced Pluripotent Stem Cell Method Compared With Current Viral-Induced Strategies

    PubMed Central

    Park, Hansoo; Kim, Dohoon; Kim, Chun-Hyung; Mills, Ryan E.; Chang, Mi-Yoon; Iskow, Rebecca Cheryl; Ko, Sanghyeok; Moon, Jung-Il; Choi, Hyun Woo; Man Yoo, Paulo Sng; Do, Jeong Tae; Han, Min-Joon; Lee, Eun Gyo; Jung, Joon Ki; Zhang, Chengsheng; Lanza, Robert

    2014-01-01

    It has recently been shown that genomic integrity (with respect to copy number variants [CNVs]) is compromised in human induced pluripotent stem cells (iPSCs) generated by viral-based ectopic expression of specific transcription factors (e.g., Oct4, Sox2, Klf4, and c-Myc). However, it is unclear how different methods for iPSC generation compare with one another with respect to CNV formation. Because array-based methods remain the gold standard for detecting unbalanced structural variants (i.e., CNVs), we have used this approach to comprehensively identify CNVs in iPSC as a proxy for determining whether our modified protein-based method minimizes genomic instability compared with retro- and lentiviral methods. In this study, we established an improved method for protein reprogramming by using partially purified reprogramming proteins, resulting in more efficient generation of iPSCs from C57/BL6J mouse hepatocytes than using protein extracts. We also developed a robust and unbiased 1 M custom array CGH platform to identify novel CNVs and previously described hot spots for CNV formation, allowing us to detect CNVs down to the size of 1.9 kb. The genomic integrity of these protein-based mouse iPSCs (p-miPSCs) was compared with miPSCs developed from viral-based strategies (i.e., retroviral: retro-miPSCs or lentiviral: lenti-miPSCs). We identified an increased CNV content in lenti-miPSCs and retro-miPSCs (29∼53 CNVs) compared with p-miPSCs (9∼10 CNVs), indicating that our improved protein-based reprogramming method maintains genomic integrity better than current viral reprogramming methods. Thus, our study, for the first time to our knowledge, demonstrates that reprogramming methods significantly influence the genomic integrity of resulting iPSCs. PMID:24763686

  14. A comparative evaluation of root canal area increase using three different nickel-titanium rotary systems: An ex vivo cone-beam computed tomographic analysis

    PubMed Central

    Deka, Adrija; Bhuyan, A.C.; Bhuyan, Darpana

    2015-01-01

    Background and Objectives: The present study was undertaken to compare and evaluate the area increase of root canals with ProTaper, iRaCe and Revo-S systems using cone beam computed tomography for analysis. Materials and Methodology: Forty five extracted human mandibular premolars having single canal and straight root were collected. Teeth were randomly assigned to three groups (n=15). Samples were decoronized by maintaining root length at 14 mm. Pre-instrumentation cone beam computed tomography scan was done after stabilizing the samples on wax blocks. The working length was determined at 1 mm short from the apical foramen by using a ISO 15 K-file tip protruding at apical foramen. Preparation was carried out according to the manufacturer's instructions. Finally, canals were instrumented upto 30/.06 apically for each group. After each instrumentation, root canals were irrigated with 2ml of 3% sodium hypochlorite solution followed by 2 ml of 17% EDTA solution. Final irrigation was done with 5ml of saline. Post instrumentation cone beam computed tomography scans of all samples in the 3 groups were acquired. Results: Mean percentage of area increase in different thirds of the canal was highest for ProTaper followed by i-RaCe and Revo-s system which was statistically significant. Interpretation and Conclusion: Root canal area increase was highest for ProTaper followed by i-Race and Revo-S systems. PMID:25684917

  15. Lysogenic Streptococcus suis isolate SS2-4 containing prophage SMP showed increased mortality in zebra fish compared to the wild-type isolate.

    PubMed

    Tang, Fang; Zhang, Wei; Lu, Chengping

    2013-01-01

    Streptococcus suis (S. suis) infection is considered to be a major problem in the swine industry worldwide. Based on the capsular type, 33 serotypes of S. suis have been described, with serotype 2 (SS2) being the most frequently isolated from diseased piglets. Little is known, however, about the pathogenesis and virulence factors of S. suis. Research on bacteriophages highlights a new area in S. suis research. A S. suis serotype 2 bacteriophage, designated SMP, has been previously isolated in our laboratory. Here, we selected a lysogenic isolate in which the SMP phage was integrated into the chromosome of strain SS2-4. Compared to the wild-type isolate, the lysogenic strain showed increased mortality in zebra fish. Moreover the sensitivity of the lysogenic strain to lysozyme was seven times higher than that of the wild-type. PMID:23326601

  16. Older Thinopyrum intermedium (Poaceae) plants exhibit superior photosynthetic tolerance to cold stress and greater increases in two photosynthetic enzymes under freezing stress compared with young plants.

    PubMed

    Jaikumar, Nikhil S; Snapp, Sieglinde S; Sharkey, Thomas D

    2016-08-01

    Effects of plant age on resource acquisition and stress tolerance processes is a largely unstudied subject in herbaceous perennials. In a field experiment, we compared rates of photosynthesis (A), ribulose-1,5-bisphosphate (RuBP) carboxylation capacity (V Cmax), maximum electron transport rate (J max), and triose phosphate utilization (TPU), as well as concentrations of Rubisco and sucrose-phosphate synthase (SPS) in 5-year-old and 2-year-old intermediate wheatgrass (Thinopyrum intermedium) under both optimal growing conditions and cold stress in early spring and autumn. This species is a relative of wheat undergoing domestication. An additional experiment compared photosynthetic rates in different cohorts at mid-season and under colder conditions. We hypothesized that photosynthetic capacity in older plants would be lower under favorable conditions but higher under cold stress. Our hypothesis was generally supported. Under cold stress, 5-year-old plants exhibited higher A, TPU, and temperature-adjusted V Cmax than younger plants, as well as 50% more SPS and 37% more Rubisco. In contrast, at mid-season, photosynthetic capacities in older plants were lower than in younger plants in one experiment, and similar in the other, independent of differences in water status. Both cohorts increased A, temperature-adjusted TPU and J max, [Rubisco], and [SPS] under cold stress, but changes were greater in older plants. Photosynthetic differences were largest at 1.2 ºC in very early spring, where older plants had 200% higher A and maintained up to 17% of their peak photosynthetic capacity. We find evidence of increased cold tolerance in older cohorts of wheatgrass, consistent with a growing body of research in woody perennials.

  17. Older Thinopyrum intermedium (Poaceae) plants exhibit superior photosynthetic tolerance to cold stress and greater increases in two photosynthetic enzymes under freezing stress compared with young plants

    PubMed Central

    Jaikumar, Nikhil S.; Snapp, Sieglinde S.; Sharkey, Thomas D.

    2016-01-01

    Effects of plant age on resource acquisition and stress tolerance processes is a largely unstudied subject in herbaceous perennials. In a field experiment, we compared rates of photosynthesis (A), ribulose-1,5-bisphosphate (RuBP) carboxylation capacity (V Cmax), maximum electron transport rate (J max), and triose phosphate utilization (TPU), as well as concentrations of Rubisco and sucrose-phosphate synthase (SPS) in 5-year-old and 2-year-old intermediate wheatgrass (Thinopyrum intermedium) under both optimal growing conditions and cold stress in early spring and autumn. This species is a relative of wheat undergoing domestication. An additional experiment compared photosynthetic rates in different cohorts at mid-season and under colder conditions. We hypothesized that photosynthetic capacity in older plants would be lower under favorable conditions but higher under cold stress. Our hypothesis was generally supported. Under cold stress, 5-year-old plants exhibited higher A, TPU, and temperature-adjusted V Cmax than younger plants, as well as 50% more SPS and 37% more Rubisco. In contrast, at mid-season, photosynthetic capacities in older plants were lower than in younger plants in one experiment, and similar in the other, independent of differences in water status. Both cohorts increased A, temperature-adjusted TPU and J max, [Rubisco], and [SPS] under cold stress, but changes were greater in older plants. Photosynthetic differences were largest at 1.2 ºC in very early spring, where older plants had 200% higher A and maintained up to 17% of their peak photosynthetic capacity. We find evidence of increased cold tolerance in older cohorts of wheatgrass, consistent with a growing body of research in woody perennials. PMID:27401911

  18. Older Thinopyrum intermedium (Poaceae) plants exhibit superior photosynthetic tolerance to cold stress and greater increases in two photosynthetic enzymes under freezing stress compared with young plants.

    PubMed

    Jaikumar, Nikhil S; Snapp, Sieglinde S; Sharkey, Thomas D

    2016-08-01

    Effects of plant age on resource acquisition and stress tolerance processes is a largely unstudied subject in herbaceous perennials. In a field experiment, we compared rates of photosynthesis (A), ribulose-1,5-bisphosphate (RuBP) carboxylation capacity (V Cmax), maximum electron transport rate (J max), and triose phosphate utilization (TPU), as well as concentrations of Rubisco and sucrose-phosphate synthase (SPS) in 5-year-old and 2-year-old intermediate wheatgrass (Thinopyrum intermedium) under both optimal growing conditions and cold stress in early spring and autumn. This species is a relative of wheat undergoing domestication. An additional experiment compared photosynthetic rates in different cohorts at mid-season and under colder conditions. We hypothesized that photosynthetic capacity in older plants would be lower under favorable conditions but higher under cold stress. Our hypothesis was generally supported. Under cold stress, 5-year-old plants exhibited higher A, TPU, and temperature-adjusted V Cmax than younger plants, as well as 50% more SPS and 37% more Rubisco. In contrast, at mid-season, photosynthetic capacities in older plants were lower than in younger plants in one experiment, and similar in the other, independent of differences in water status. Both cohorts increased A, temperature-adjusted TPU and J max, [Rubisco], and [SPS] under cold stress, but changes were greater in older plants. Photosynthetic differences were largest at 1.2 ºC in very early spring, where older plants had 200% higher A and maintained up to 17% of their peak photosynthetic capacity. We find evidence of increased cold tolerance in older cohorts of wheatgrass, consistent with a growing body of research in woody perennials. PMID:27401911

  19. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow-derived counterparts.

    PubMed

    Blashki, Daniel; Murphy, Matthew B; Ferrari, Mauro; Simmons, Paul J; Tasciotti, Ennio

    2016-01-01

    In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit-fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit-fibroblasts. The composite phenotype Lin(-)/CD45(-)/CD31(-)/VLA-1(+)/Thy-1(+) enriched for clonogenic mesenchymal stem cells solely from cortical bone-derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone-derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies. PMID:27579159

  20. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow–derived counterparts

    PubMed Central

    Blashki, Daniel; Murphy, Matthew B; Ferrari, Mauro; Simmons, Paul J; Tasciotti, Ennio

    2016-01-01

    In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit–fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit–fibroblasts. The composite phenotype Lin−/CD45−/CD31−/VLA-1+/Thy-1+ enriched for clonogenic mesenchymal stem cells solely from cortical bone–derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone–derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies. PMID:27579159

  1. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    PubMed Central

    2011-01-01

    Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p < 0.05 for the overall physiologic state effect (lactation vs. control), and a within tissue pairwise comparison of p < 0.01. The proportion of false positives, an estimate of the ratio of false positives in the list of differentially expressed genes, was calculated for each tissue. The number of differentially expressed genes was 420 in the liver, 337 in the duodenum, 402 in the jejunum, and 523 in the ileum. The list of differentially expressed genes was in turn analyzed by Ingenuity Pathways Analysis (IPA) to detect biological pathways that were overrepresented. In all tissues, sterol regulatory element binding protein (Srebp)-regulated genes involved in cholesterol synthesis showed increased mRNA expression, with the fewest changes detected in the jejunum. We detected increased Scap mRNA in the liver only, suggesting an explanation for the difference in response to lactation between the liver and small intestine. Expression of Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In

  2. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1)*

    PubMed Central

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S.; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P.

    2015-01-01

    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted. PMID:26004777

  3. Comparative Proteomics of Ovarian Cancer Aggregate Formation Reveals an Increased Expression of Calcium-activated Chloride Channel Regulator 1 (CLCA1).

    PubMed

    Musrap, Natasha; Tuccitto, Alessandra; Karagiannis, George S; Saraon, Punit; Batruch, Ihor; Diamandis, Eleftherios P

    2015-07-10

    Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted.

  4. Increased risk of virologic failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: data from the ICONA cohort.

    PubMed

    Saracino, A; Lorenzini, P; Lo Caputo, S; Girardi, E; Castelli, F; Bonfanti, P; Rusconi, S; Caramello, P; Abrescia, N; Mussini, C; Monno, L; d'Arminio Monforte, A

    2016-03-01

    Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004-2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) >200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL >200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67-0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8-8.5) in migrants and 2.7 in natives (95% CI 2.2-3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25-2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01-1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor-based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives.

  5. One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients

    PubMed Central

    Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E.; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J.; Valdez, Herlindo; Fernandez, Maria Luz

    2015-01-01

    There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35–65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation. PMID:25970149

  6. One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients.

    PubMed

    Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J; Valdez, Herlindo; Fernandez, Maria Luz

    2015-05-01

    There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35-65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation. PMID:25970149

  7. Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion.

    PubMed

    Gautier, J F; Milner, M R; Elam, E; Chen, K; Ravussin, E; Pratley, R E

    1999-01-01

    Pima Indians are insulin resistant and hyperinsulinaemic compared with Caucasians. We investigated whether abdominal fat distribution was different between Pimas and Caucasians and whether differences in the amount of visceral fat explained metabolic differences between the groups. Total body fat (absorptiometry) and abdominal fat distribution at L4-L5 (magnetic resonance imaging) were compared in 20 Pima Indians (10 men/10 women) and 20 age-, sex- and BMI-matched Caucasians. Insulin action was measured as glucose disposal during a two-step hyperinsulinaemic-euglycaemic glucose clamp and insulin secretion was assessed in response to oral and intravenous glucose tolerance tests. By design, percent body fat was similar in Pimas and Caucasians. Abdominal visceral and subcutaneous adipose tissue areas were also similar in the two groups (151+/-16 vs 139+/-15 cm2 and 489+/-61 vs 441+/-7 cm2 respectively). Plasma insulin concentrations were higher in Pimas than Caucasians in the fasting state (27+/-6 vs 11+/-2 mU/ml; p < 0.01) and after a 75-g oral glucose load (area under the curve 19975+/-2626 vs 9293+/-1847 mU x l(-1) x 180 min(-1); p < 0.005). Glucose disposal was lower in Pimas than Caucasians during both steps of the clamp and negatively correlated (after adjustment for percent body fat and sex) with visceral adipose tissue in Caucasians (partial r = -0.51, p = 0.03), but not in Pima Indians (r = -0.03, p = 0.92). Insulin secretion was not related to visceral fat independently of percent body fat in either group. We conclude that a relative increase in visceral fat does not explain insulin resistance and hyperinsulinaemia in Pima Indians. PMID:10027574

  8. One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients.

    PubMed

    Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J; Valdez, Herlindo; Fernandez, Maria Luz

    2015-05-11

    There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35-65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation.

  9. Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter

    PubMed Central

    Giorgi Rossi, P; Fortunato, C; Barbarino, P; Boveri, S; Caroli, S; Del Mistro, A; Ferro, A; Giammaria, C; Manfredi, M; Moretto, T; Pasquini, A; Sideri, M; Tufi, M C; Cogo, C; Altobelli, E; Moretto, Tina; Barro, Carmen; Cinquetti, Sandro; Bittesini, Lucia; Fantin, Gianpiero; Ferro, Antonio; Penon, Gabriella; Bertazzo, Sandra; Toniolo, Laura; Farrugio, Angelo; Cocco, Patrizia; Gerace, Pierfrancesco; Capuzzo, Sonia; Vitaliani, Mariangela; Fioravanti, Milena; Benvegnù, Cristina; Del Mistro, Annarosa; Frayle, Helena; Rizzi, Martina; Trevisan, Rossana; Cogo, Carla; Zorzi, Manuel; Fedato, Chiara; Fortunato, Carmine; Scarselli, Giorgio; Altobelli, Emma; Lattanzi, Amedeo; Caroli, Stefania; Rossi, Paolo Giorgi; La Terra, Katiuscia; Barbarino, Paolo; Tufi, Maria Concetta; Gimmaria, Carla; Manfredi, Marilena; Pasquini, Adriana; Sideri, Mario; Boveri, Sara

    2015-01-01

    Background: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. Methods: Women aged 30–64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. Results: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60–1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86–1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I2, 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. Conclusions: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre. PMID:25633037

  10. Increased risk of virologic failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: data from the ICONA cohort.

    PubMed

    Saracino, A; Lorenzini, P; Lo Caputo, S; Girardi, E; Castelli, F; Bonfanti, P; Rusconi, S; Caramello, P; Abrescia, N; Mussini, C; Monno, L; d'Arminio Monforte, A

    2016-03-01

    Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004-2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) >200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL >200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67-0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8-8.5) in migrants and 2.7 in natives (95% CI 2.2-3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25-2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01-1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor-based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives. PMID:26551839

  11. Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis

    PubMed Central

    ZHANG, GUANGYUAN; WANG, DANDAN; MIAO, SHUAI; ZOU, XIANGYU; LIU, GUOHUA; ZHU, YINGJIAN

    2016-01-01

    The potential involvement of the endocrine/paracrine mechanisms in the mesenchymal stromal cells (MSCs) therapy for acute kidney injury (AKI) has been increasingly studied. The aim of the present meta-analysis was to systematically review the therapeutic role of MSC-conditioned medium (CM) or MSCs released by extracellular vesicles (Evs) for the treatment of AKI in rodent models. Studies were identified using PubMed and Scopus databases using a custom search strategy and eligibility criteria. Data regarding serum creatinine (SCr) concentration, CM or Evs, measurement time point, AKI model (toxic or non-toxic) and other parameters, including delivery route, animal type and animal numbers, were extracted. Pooled analysis and subgroup analysis as well as multivariable meta-regression were performed. Heterogeneity and publication bias were also investigated. A total of 13 studies were included and analyzed. Pooled analysis showed reduced SCr (0.93 [0.67, 1.20], mg/dl) in rodent models of AKI after CM/Evs therapy. The results of the subgroup analysis suggested that Evs induced an increased therapeutic effect, in the form of SCr reduction, as compared with CM (P=0.05). There were also other significant influential factors for SCr reduction including measurement time point (P=0.0004) and therapeutic time point (P<0.0001) after surgery. By contrast, parameters such as delivery route, injury type and cell type were not significant influential factors. Multivariable meta-regression analysis showed that measurement time point (P=0.041), therapeutic time point (P=0.03), Evs or CM (P=0.0003) and cell type (P<0.0001) were influential factors in the reduction of SCr. The present meta-analysis indicates that CM or Evs derived from MSCs are able to improve the impaired renal function in rodents modelling AKI. Compared with CM, Evs may produce a more marked therapeutic effect in recovery from renal failure. In addition, CM or Evs administration in early stages of AKI may result in

  12. Comparative evaluation of the relative efficacy of the free mucosal graft and periosteal fenestration for increasing the vestibular depth - A clinical study

    PubMed Central

    Yadav, Nisha; Khattak, Braham Prakash; Misra, Shobhana; Sharma, Anamika

    2014-01-01

    Purpose: The aim of the present study was to compare the periosteal fenestration (PF) and free mucosal graft (FMG) techniques in mandibular anterior region to increase the vestibular depth. Methodology: A total of 20 systemically healthy cases (10 patients in each group) with shallow vestibular depth and reduced width of attached gingiva in lower anterior region were included in the present study. Clinical parameters recorded included Gingival index (GI), Plaque index (PI), Oral hygiene index simplified (OHI S), Vestibular depth (VD), width of attached gingiva and post operative discomfort. Findings: The results at the end of 3 months showed that the mean GI, PI, OHI S decreased significantly and remained low throughout the study period. The mean gain in percentage of vestibular depth at the end of 3 months for group 1(PF) was 48.4% with relapse of 7.2% from the baseline. For group 2 (FMG), the mean gain in percentage of vestibular depth at the end of 3 months for was 50% with relapse of 6.2% from the baseline. The mean gain in percentage of attached gingiva at 3 months for group 1 and 2 was 65.9% and 74%, respectively. In comparison of group 1 and 2, group 2 showed better results in terms of increasing the vestibular depth and attached gingiva than group 1 although the intergroup comparison was not statistically significant. Conclusion: When aim of the clinician is to treat a patient with shallow vestibule together with reduced width of attached gingiva, the use of periosteal fenestration yields similar results to that of FMG. PMID:25191075

  13. The Alteration of Life History Traits and Increased Success of Halipegus eccentricus Through the Use of a Paratenic Host: A Comparative Study.

    PubMed

    Stigge, Heather A; Bolek, Matthew G

    2015-12-01

    Complex life cycles are a hallmark characteristic of many parasites; however, little is known about the process by which life cycles become more complex through the addition of hosts. Paratenic hosts are present in the life cycles of several phylogenetically distinct groups of helminths; this suggests that they may play a key role during this process. This study examined the development of metacercariae of Halipegus eccentricus within intermediate microcrustacean and odonate paratenic hosts. Then a comparative approach was used to evaluate how life history traits of H. eccentricus within the anuran definitive hosts differ between metacercariae of the same age that developed within an intermediate ostracod host or a paratenic odonate host. The results of this study indicate that metacercariae of H. eccentricus do not grow at the same rate in different intermediate hosts, and significant differences exist in growth within intermediate and paratenic hosts. Individuals from odonate paratenic hosts always had larger bodies and suckers than those of metacercariae of the same age that develop within microcrustacean intermediate hosts. Furthermore, metacercariae from odonates were more successful in establishing and migrating in definitive anuran hosts. Last, individuals from paratenic hosts began reproducing earlier within anuran definitive hosts than age-matched worms that develop within the intermediate hosts. Collectively these results suggest that the variation in body and sucker sizes within odonate and microcrustacean hosts may carry over to the definitive host and in the case of H. eccentricus using the paratenic host increases transmission and alters other life history traits within definitive hosts. These results indicate that using a paratenic host can affect the success of parasites in subsequent hosts, and therefore these hosts may provide benefits other than just increasing transmission by bridging an ecological gap. PMID:26301445

  14. The Alteration of Life History Traits and Increased Success of Halipegus eccentricus Through the Use of a Paratenic Host: A Comparative Study.

    PubMed

    Stigge, Heather A; Bolek, Matthew G

    2015-12-01

    Complex life cycles are a hallmark characteristic of many parasites; however, little is known about the process by which life cycles become more complex through the addition of hosts. Paratenic hosts are present in the life cycles of several phylogenetically distinct groups of helminths; this suggests that they may play a key role during this process. This study examined the development of metacercariae of Halipegus eccentricus within intermediate microcrustacean and odonate paratenic hosts. Then a comparative approach was used to evaluate how life history traits of H. eccentricus within the anuran definitive hosts differ between metacercariae of the same age that developed within an intermediate ostracod host or a paratenic odonate host. The results of this study indicate that metacercariae of H. eccentricus do not grow at the same rate in different intermediate hosts, and significant differences exist in growth within intermediate and paratenic hosts. Individuals from odonate paratenic hosts always had larger bodies and suckers than those of metacercariae of the same age that develop within microcrustacean intermediate hosts. Furthermore, metacercariae from odonates were more successful in establishing and migrating in definitive anuran hosts. Last, individuals from paratenic hosts began reproducing earlier within anuran definitive hosts than age-matched worms that develop within the intermediate hosts. Collectively these results suggest that the variation in body and sucker sizes within odonate and microcrustacean hosts may carry over to the definitive host and in the case of H. eccentricus using the paratenic host increases transmission and alters other life history traits within definitive hosts. These results indicate that using a paratenic host can affect the success of parasites in subsequent hosts, and therefore these hosts may provide benefits other than just increasing transmission by bridging an ecological gap.

  15. Tick-susceptible Bos taurus cattle display an increased cellular response at the site of larval Rhipicephalus (Boophilus) microplus attachment, compared with tick-resistant Bos indicus cattle.

    PubMed

    Piper, Emily K; Jackson, Louise A; Bielefeldt-Ohmann, Helle; Gondro, Cedric; Lew-Tabor, Ala E; Jonsson, Nicholas N

    2010-03-15

    Cattle demonstrate divergent and heritable phenotypes of resistance and susceptibility to infestation with the cattle tick Rhipicephalus (Boophilus) microplus. Bos indicus cattle are generally more resistant to tick infestation than Bos taurus breeds although large variations in resistance can occur within subspecies and within breed. Increased tick resistance has been previously associated with an intense hypersensitivity response in B. taurus breeds; however, the mechanism by which highly resistant B. indicus cattle acquire and sustain high levels of tick resistance remains to be elucidated. Using the commercially available Affymetrix microarray gene expression platform, together with histological examination of the larval attachment site, this study aimed to describe those processes responsible for high levels of tick resistance in Brahman (B. indicus) cattle that differ from those in low-resistance Holstein-Friesian (B. taurus) cattle. We found that genes involved in inflammatory processes and immune responsiveness to infestation by ticks, although up-regulated in tick-infested Holstein-Friesian cattle, were not up-regulated in Brahman cattle. In contrast, genes encoding constituents of the extracellular matrix were up-regulated in Brahmans. Furthermore, the susceptible Holstein-Friesian animals displayed a much greater cellular inflammatory response at the site of larval R. microplus attachment compared with the tick-resistant Brahman cattle. PMID:19852965

  16. Comparative genome-based identification of a cell wall-anchored protein from Lactobacillus plantarum increases adhesion of Lactococcus lactis to human epithelial cells

    PubMed Central

    Zhang, Bo; Zuo, Fanglei; Yu, Rui; Zeng, Zhu; Ma, Huiqin; Chen, Shangwu

    2015-01-01

    Adhesion to host cells is considered important for Lactobacillus plantarum as well as other lactic acid bacteria (LAB) to persist in human gut and thus exert probiotic effects. Here, we sequenced the genome of Lt. plantarum strain NL42 originating from a traditional Chinese dairy product, performed comparative genomic analysis and characterized a novel adhesion factor. The genome of NL42 was highly divergent from its closest neighbors, especially in six large genomic regions. NL42 harbors a total of 42 genes encoding adhesion-associated proteins; among them, cwaA encodes a protein containing multiple domains, including five cell wall surface anchor repeat domains and an LPxTG-like cell wall anchor motif. Expression of cwaA in Lactococcus lactis significantly increased its autoaggregation and hydrophobicity, and conferred the new ability to adhere to human colonic epithelial HT-29 cells by targeting cellular surface proteins, and not carbohydrate moieties, for CwaA adhesion. In addition, the recombinant Lc. lactis inhibited adhesion of Staphylococcus aureus and Escherichia coli to HT-29 cells, mainly by exclusion. We conclude that CwaA is a novel adhesion factor in Lt. plantarum and a potential candidate for improving the adhesion ability of probiotics or other bacteria of interest. PMID:26370773

  17. Comparative genome-based identification of a cell wall-anchored protein from Lactobacillus plantarum increases adhesion of Lactococcus lactis to human epithelial cells.

    PubMed

    Zhang, Bo; Zuo, Fanglei; Yu, Rui; Zeng, Zhu; Ma, Huiqin; Chen, Shangwu

    2015-01-01

    Adhesion to host cells is considered important for Lactobacillus plantarum as well as other lactic acid bacteria (LAB) to persist in human gut and thus exert probiotic effects. Here, we sequenced the genome of Lt. plantarum strain NL42 originating from a traditional Chinese dairy product, performed comparative genomic analysis and characterized a novel adhesion factor. The genome of NL42 was highly divergent from its closest neighbors, especially in six large genomic regions. NL42 harbors a total of 42 genes encoding adhesion-associated proteins; among them, cwaA encodes a protein containing multiple domains, including five cell wall surface anchor repeat domains and an LPxTG-like cell wall anchor motif. Expression of cwaA in Lactococcus lactis significantly increased its autoaggregation and hydrophobicity, and conferred the new ability to adhere to human colonic epithelial HT-29 cells by targeting cellular surface proteins, and not carbohydrate moieties, for CwaA adhesion. In addition, the recombinant Lc. lactis inhibited adhesion of Staphylococcus aureus and Escherichia coli to HT-29 cells, mainly by exclusion. We conclude that CwaA is a novel adhesion factor in Lt. plantarum and a potential candidate for improving the adhesion ability of probiotics or other bacteria of interest.

  18. Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women.

    PubMed

    Juntunen, K S; Mazur, W M; Liukkonen, K H; Uehara, M; Poutanen, K S; Adlercreutz, H C; Mykkänen, H M

    2000-12-01

    Rye is an important source of plant lignans in Finland. In the present crossover trial we wanted to study the effect of rye bread as part of the usual diet on serum and urine enterolactone (ENL) concentrations in healthy volunteers. Eighteen men aged 43 (sem 2.0) years and twenty-one women aged 43 (sem 1.6) years consumed wholemeal rye bread and white wheat bread in random order for 4 weeks. The bread periods were separated by a 4 week wash-out period. The breads provided at least 20% of the daily energy intake. The mean intakes of rye bread were 219 (sem 14.6) and 162 (sem 5.3) g/d and those of wheat bread were 200 (sem 9.6) and 153 (sem 5.8) g/d for men and women respectively. Blood samples were collected from all subjects and three 24 h urine samples were collected from ten men and twelve women at the end of both bread periods for the determination of serum concentration and urinary excretion of ENL. The mean serum ENL concentrations in both men and women at the beginning of baseline period and at the end of the rye-bread period remained constant and were significantly higher than those at the end of the wheat-bread period. Correspondingly, daily urinary ENL excretion increased significantly during the rye-bread period compared with the wheat-bread period and was 5- and 10-fold higher in men and women respectively in comparison with the amount of plant lignan precursors measured in the rye bread. These data indicate the presence of other precursors for ENL in rye which are not detected by the current method of measuring plant lignans in food. The possible role of fibre in enhancement of the formation of mammalian lignans from their plant precursors in the gut also remains to be determined.

  19. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

    PubMed

    Haffner, S M; D'Agostino, R; Saad, M F; Rewers, M; Mykkänen, L; Selby, J; Howard, G; Savage, P J; Hamman, R F; Wagenknecht, L E

    1996-06-01

    The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non

  20. More efficient mastication allows increasing intake without compromising digestibility or necessitating a larger gut: comparative feeding trials in banteng (Bos javanicus) and pygmy hippopotamus (Hexaprotodon liberiensis).

    PubMed

    Schwarm, Angela; Ortmann, Sylvia; Wolf, Christian; Streich, W Jürgen; Clauss, Marcus

    2009-04-01

    The digestion of plant material in mammalian herbivores basically depends on the chemical and structural composition of the diet, the mean particle size to which the forage is processed, and the ingesta retention time. These different factors can be influenced by the animal, and they can presumably compensate for each other. The pygmy hippopotamus, a non-ruminating foregut fermenter, has longer mean retention times than ruminants; however hippos do not achieve higher (fibre) digestibilities on comparable diets, which could be due to ineffective mastication. We performed feeding trials with six pygmy hippos (Hexaprotodon liberiensis) and six banteng cattle (Bos javanicus) on a grass diet. As predicted, both species achieved similar dry matter, organic matter, crude protein and gross energy digestibilities. However, neutral and acid detergent fibre digestibility was lower in pygmy hippos. Apparently, in these species, fibre digestibility was more influenced by particle size, which was larger in pygmy hippos compared to banteng, than by retention time. In spite of their higher relative food intake, the banteng in this study did not have greater relative gut fills than the hippos. Ruminants traditionally appear intake-limited when compared to equids, because feed particles above a certain size cannot leave the rumen. But when compared to nonruminating foregut fermenters, rumination seems to free foregut fermenters from an intrinsic food intake limitation. The higher energy intakes and metabolic rates in wild cattle compared to hippos could have life-history consequences, such as a higher relative reproductive rate.

  1. More efficient mastication allows increasing intake without compromising digestibility or necessitating a larger gut: comparative feeding trials in banteng (Bos javanicus) and pygmy hippopotamus (Hexaprotodon liberiensis).

    PubMed

    Schwarm, Angela; Ortmann, Sylvia; Wolf, Christian; Streich, W Jürgen; Clauss, Marcus

    2009-04-01

    The digestion of plant material in mammalian herbivores basically depends on the chemical and structural composition of the diet, the mean particle size to which the forage is processed, and the ingesta retention time. These different factors can be influenced by the animal, and they can presumably compensate for each other. The pygmy hippopotamus, a non-ruminating foregut fermenter, has longer mean retention times than ruminants; however hippos do not achieve higher (fibre) digestibilities on comparable diets, which could be due to ineffective mastication. We performed feeding trials with six pygmy hippos (Hexaprotodon liberiensis) and six banteng cattle (Bos javanicus) on a grass diet. As predicted, both species achieved similar dry matter, organic matter, crude protein and gross energy digestibilities. However, neutral and acid detergent fibre digestibility was lower in pygmy hippos. Apparently, in these species, fibre digestibility was more influenced by particle size, which was larger in pygmy hippos compared to banteng, than by retention time. In spite of their higher relative food intake, the banteng in this study did not have greater relative gut fills than the hippos. Ruminants traditionally appear intake-limited when compared to equids, because feed particles above a certain size cannot leave the rumen. But when compared to nonruminating foregut fermenters, rumination seems to free foregut fermenters from an intrinsic food intake limitation. The higher energy intakes and metabolic rates in wild cattle compared to hippos could have life-history consequences, such as a higher relative reproductive rate. PMID:19135544

  2. Increase in Periodontal Interleukin-1β Gene Expression Following Osseous Resective Surgery Using Conventional Rotary Instruments Compared with Piezosurgery: A Split-Mouth Randomized Clinical Trial.

    PubMed

    Aimetti, Mario; Ferrarotti, Francesco; Bergandi, Loredana; Saksing, Laura; Parducci, Francesca; Romano, Federica

    2016-01-01

    The purpose of this study was to evaluate the early inflammatory response following osseous resective surgery (ORS) with Piezosurgery compared to commonly used diamond burs. A sample was selected of 24 bilateral posterior sextants requiring ORS in 12 chronic periodontitis patients in a split-mouth design. In 12 sextants, bone recontouring was performed using a piezoelectric device. In the contralateral sextants, rotary instruments were used. Sextants treated with Piezosurgery obtained similar 12-month clinical results but lower postsurgical gene expression of interleukin-1β (IL-1β), a well-known proinflammatory cytokine, and lower patient morbidity compared with sextants treated with rotary instruments. In spite of the longer surgical time, the use of Piezosurgery for ORS seems to promote more favorable wound healing compared with rotary instruments, as the lower pain and the low levels of IL-1β mRNA at the surgical sites suggest a milder underlying inflammatory response. PMID:27333006

  3. Impaired fasting glucose is associated with increased severity of subclinical coronary artery disease compared to patients with diabetes and normal fasting glucose: evaluation by coronary computed tomographic angiography

    PubMed Central

    Gurudevan, Swaminatha; Garg, Pankaj; Malik, Shaista; Khattar, Ramni; Saremi, Farhood; Hecht, Harvey; DeMaria, Anthony; Narula, Jagat

    2016-01-01

    Objective This study was designed to evaluate the severity of subclinical atherosclerosis in patients with asymptomatic impaired fasting glucose (IFG) compared to those with diabetes mellitus (DM) and normal fasting glucose (NFG), as measured by coronary computed tomographic angiography (CCTA). Design Subjects were divided into three groups: NFG (<100 mg/dL), IFG (100–125 mg/dL) and DM. Coronary artery calcium on non-contrast CT and plaque analysis on CCTA were performed. Setting University hospital, single centre. Participants 216 asymptomatic participants prospectively underwent CCTA for the evaluation of coronary artery disease (CAD). Primary and secondary outcome measures Atherosclerotic plaque burden in IFG compared to NFG patients. Results 2664 segments were analysed in 120 NFG, 44 IFG and 52 DM participants. The mean calcium scores were 178±395, 259±510 and 414±836 for NFG, IFG and DM, respectively (p=0·037). The mean plaque burdens in the NFG, IFG and DM groups were 0.31±0.45, 0.50±0.69 and 0.68±0.69, respectively (p=0·0007). A greater proportion of patients with DM (19/52, 36.5%) and IFG (13/44, 29.5%) had obstructive CAD compared to those with NFG (16/120, 13.3%) (p=0.0015). The number of segments with severe disease was significantly higher in the DM (60/637, 9.4%) and IFG (42/539, 7.8%) groups compared to that in the NFG group (34/1488, 2.3%) (p=0.0001). Conclusions (1) IFG and DM have significantly higher, but comparable, calcium scores, plaque burden and obstructive CAD compared to NFG in asymptomatic individuals. (2) Pending corroboration by other reports, more intensive efforts may be devoted to the evaluation and treatment of patients with IFG. PMID:27531720

  4. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls.

    PubMed

    Heimark, Douglas; McAllister, Jan; Larner, Joseph

    2014-01-01

    Previous studies from our and other labs have shown that insulin resistance is associated with an inositol imbalance of excess myo-inositol and deficient chiro-inositol together with a deficiency of myo-inositol to chiro-inositol epimerase in vivo and in vitro. In this report, we utilized well characterized theca cells from normal cycling women, with normal insulin sensitivity, and theca cells from women with polycystic ovary syndrome (PCOS), with increased insulin sensitivity to examine the myo-inositol to chiro-inisitol (M/C) ratio and the myo-inositol to chiro-inositol epimerase activity. PCOS theca cells with increased insulin sensitivity were specifically used to investigate whether the inositol imbalance and myo-inositol to chiro-inositol epimerase are regulated in a similar or the opposite direction than that observed in insulin resistant cells. The results of these studies are the first to demonstrate that in insulin sensitive PCOS theca cells the inositol imbalance goes in the opposite direction to that observed in insulin resistant cells, and there is a decreased M/C ratio and an increased myo-inositol to chiro-inositol epimerase activity. Further biochemical and genetic studies will probe the mechanisms involved.

  5. Increased WD-repeat containing protein 1 in interstitial fluid from ovarian carcinomas shown by comparative proteomic analysis of malignant and healthy gynecological tissue.

    PubMed

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Wiig, Helge; Tenstad, Olav

    2013-11-01

    We aimed to identify differentially expressed proteins in interstitial fluid from ovarian cancer employing multiple fractioning and high resolution mass spectrometry-based proteomic analysis, and asked whether specific proteins that may serve as biomarker candidates or therapeutic targets could be identified. High throughput proteomics was conducted on immunodepleted and fractioned interstitial fluid from pooled samples of ovarian carcinomas, using endometrial carcinomas and healthy ovarian tissue as controls. Differential analysis revealed the up-regulation of extracellular proteasomes in tumor interstitial fluid compared to the healthy control. Moreover, a number of differentially expressed proteins in interstitial fluid from ovarian carcinomas compared with control tissues were identified. Detection of proteasome 20S related proteins in TIF compared to IF from healthy tissue indicates that the 20S proteasome can have a role in the tumor microenvironment. Six selected proteins, CEACAM5, FREM2, MUC5AC, TFF3, PYCARD and WDR1, were independently validated in individual tumor lysates from ovarian carcinomas by multiple reaction monitoring initiated detection and sequence analysis, Western blot and/or selected reaction monitoring. Quantification of specific proteins revealed substantial heterogeneity between individual samples. Nevertheless, WD repeat-containing protein 1 was confirmed as being significantly overexpressed in interstitial fluid from ovarian carcinomas compared to healthy ovarian tissue by Orbitrap analysis of individual native interstitial fluid from ovarian and endometrial carcinomas and healthy ovarian tissue. We suggest that this protein should be explored as a therapeutic target in ovarian carcinomas. This article is part of a Special Issue entitled: An Updated Secretome.

  6. Can we build the cowherd by increasing longevity of females?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing longevity of beef cows by decreasing proportion culled due to reproductive failure reduces number of replacements needed to sustain a constant herd size. Rate of reproductive failure varies with cow age, where failure in cows younger than 4 yr of age can be 2-fold greater than in cows 4 ...

  7. Comparative modeling of DszC, an enzyme in biodesulfurization, and performing in silico point mutation for increasing tendency to oil.

    PubMed

    Torktaz, Ibrahim; Etemadifar, Zahra; Derikvand, Peyman

    2012-01-01

    Desulfurization protein named DszC from Rhodococcus erythropolis is the key enzyme for biodesulforization of dibenzothiophene (DBT) in 4S pathway, which is a pathway with four enzymes. DszC enzyme biodesulfurizes DBT and its derivatives in oil components and biphasic systems. It functions well at the oil- water interface. In this study point mutation performed in DszC enzyme regarding to increase protein hydrophobicity and stability for application in immobilized form. 3D model of DszC predicted using Phyre2, SAM-T08 and M4t servers. I-Mutant 2 server used to determine potential spots for point mutation, and Molegro Virtual Docker (MVD) used for performing point mutation on 3D model. Hydrophobicity plots generated by Bioedit version 7.0.8.0 in Kyte-Doolittle scale indicated that protein hydrophobicity is increased after mutation. Also protein stability increased 26.11 units in scale of DDC2. PMID:22493530

  8. Increased water contamination and grow-out Pekin duck mortality when raised with water troughs compared to pin-metered water lines using a United States management system.

    PubMed

    Schenk, A; Porter, A L; Alenciks, E; Frazier, K; Best, A A; Fraley, S M; Fraley, G S

    2016-04-01

    Controversy has developed as to whether or not pin-metered water lines or water troughs are more appropriate for Pekin ducks. We hypothesized that water troughs would show improved duck body conditions and environmental quality compared to pin-metered water lines. To test this hypothesis, we housed ducks in 2 barns, one with water lines and one with water troughs. Water troughs were constructed to meet RSPCA guidelines for number and density of ducks and with recently described verandas. Ducks were divided into 4 pens per barn (n=1,000 ducks/pen). The study was then repeated (n=8 pens per water source) in a cross-over design so the barns each contained the opposite water source to the first experiment. We scored the ducks' body condition using an established scoring rubric and analyzed using SAS Proc GLM-Mix as binomial data. Ducks housed with water troughs showed higher (thus worse condition; P<0.001) scores for eyes, nostrils, feather quality, feather cleanliness, and foot pads. We also compared water condition, water quality, and duck mortality using a Student t test for both water sources each week. We found that the water troughs showed higher iron (P<0.001), nitrites (P<0.001), pH (P<0.01), and bacterial growth (P<0.001). The bacterial growth was shown to have higher (P<0.001)E. coli, coliforms, and Staphylococcusin the water troughs. Water lines typically showed no bacterial growth in culture-based assays. Ducks housed with water troughs used greater (P=0.001) volumes of water compared to ducks housed with water lines. Ducks with water troughs also showed a greater percent (P=0.008) mortality at all ages compared to ducks with water lines. These data suggest that water troughs may not be beneficial for duck welfare and could adversely impact both environment and duck or human health. PMID:26769272

  9. Increased water contamination and grow-out Pekin duck mortality when raised with water troughs compared to pin-metered water lines using a United States management system.

    PubMed

    Schenk, A; Porter, A L; Alenciks, E; Frazier, K; Best, A A; Fraley, S M; Fraley, G S

    2016-04-01

    Controversy has developed as to whether or not pin-metered water lines or water troughs are more appropriate for Pekin ducks. We hypothesized that water troughs would show improved duck body conditions and environmental quality compared to pin-metered water lines. To test this hypothesis, we housed ducks in 2 barns, one with water lines and one with water troughs. Water troughs were constructed to meet RSPCA guidelines for number and density of ducks and with recently described verandas. Ducks were divided into 4 pens per barn (n=1,000 ducks/pen). The study was then repeated (n=8 pens per water source) in a cross-over design so the barns each contained the opposite water source to the first experiment. We scored the ducks' body condition using an established scoring rubric and analyzed using SAS Proc GLM-Mix as binomial data. Ducks housed with water troughs showed higher (thus worse condition; P<0.001) scores for eyes, nostrils, feather quality, feather cleanliness, and foot pads. We also compared water condition, water quality, and duck mortality using a Student t test for both water sources each week. We found that the water troughs showed higher iron (P<0.001), nitrites (P<0.001), pH (P<0.01), and bacterial growth (P<0.001). The bacterial growth was shown to have higher (P<0.001)E. coli, coliforms, and Staphylococcusin the water troughs. Water lines typically showed no bacterial growth in culture-based assays. Ducks housed with water troughs used greater (P=0.001) volumes of water compared to ducks housed with water lines. Ducks with water troughs also showed a greater percent (P=0.008) mortality at all ages compared to ducks with water lines. These data suggest that water troughs may not be beneficial for duck welfare and could adversely impact both environment and duck or human health.

  10. Increased water contamination and grow-out Pekin duck mortality when raised with water troughs compared to pin-metered water lines using a United States management system

    PubMed Central

    Schenk, A.; Porter, A. L.; Alenciks, E.; Frazier, K.; Best, A. A.; Fraley, S. M.; Fraley, G. S.

    2016-01-01

    Controversy has developed as to whether or not pin-metered water lines or water troughs are more appropriate for Pekin ducks. We hypothesized that water troughs would show improved duck body conditions and environmental quality compared to pin-metered water lines. To test this hypothesis, we housed ducks in 2 barns, one with water lines and one with water troughs. Water troughs were constructed to meet RSPCA guidelines for number and density of ducks and with recently described verandas. Ducks were divided into 4 pens per barn (n = 1,000 ducks/pen). The study was then repeated (n = 8 pens per water source) in a cross-over design so the barns each contained the opposite water source to the first experiment. We scored the ducks’ body condition using an established scoring rubric and analyzed using SAS Proc GLM-Mix as binomial data. Ducks housed with water troughs showed higher (thus worse condition; P < 0.001) scores for eyes, nostrils, feather quality, feather cleanliness, and foot pads. We also compared water condition, water quality, and duck mortality using a Student t test for both water sources each week. We found that the water troughs showed higher iron (P < 0.001), nitrites (P < 0.001), pH (P < 0.01), and bacterial growth (P < 0.001). The bacterial growth was shown to have higher (P < 0.001) E. coli, coliforms, and Staphylococcus in the water troughs. Water lines typically showed no bacterial growth in culture-based assays. Ducks housed with water troughs used greater (P = 0.001) volumes of water compared to ducks housed with water lines. Ducks with water troughs also showed a greater percent (P = 0.008) mortality at all ages compared to ducks with water lines. These data suggest that water troughs may not be beneficial for duck welfare and could adversely impact both environment and duck or human health. PMID:26769272

  11. Increasing organizational energy conservation behaviors: Comparing the theory of planned behavior and reasons theory for identifying specific motivational factors to target for change

    NASA Astrophysics Data System (ADS)

    Finlinson, Scott Michael

    Social scientists frequently assess factors thought to underlie behavior for the purpose of designing behavioral change interventions. Researchers commonly identify these factors by examining relationships between specific variables and the focal behaviors being investigated. Variables with the strongest relationships to the focal behavior are then assumed to be the most influential determinants of that behavior, and therefore often become the targets for change in a behavioral change intervention. In the current proposal, multiple methods are used to compare the effectiveness of two theoretical frameworks for identifying influential motivational factors. Assessing the relative influence of all factors and sets of factors for driving behavior should clarify which framework and methodology is the most promising for identifying effective change targets. Results indicated each methodology adequately predicted the three focal behaviors examined. However, the reasons theory approach was superior for predicting factor influence ratings compared to the TpB approach. While common method variance contamination had minimal impact on the results or conclusions derived from the present study's findings, there were substantial differences in conclusions depending on the questionnaire design used to collect the data. Examples of applied uses of the present study are discussed.

  12. CELL RESPIRATION STUDIES : II. A COMPARATIVE STUDY OF THE OXYGEN CONSUMPTION OF BLOOD FROM NORMAL INDIVIDUALS AND PATIENTS WITH INCREASED LEUCOCYTE COUNTS (SEPSIS; CHRONIC MYELOGENOUS LEUCEMIA).

    PubMed

    Daland, G A; Isaacs, R

    1927-06-30

    1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used. 2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood. 3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air. 5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature. 6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg's reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells.

  13. Human-specific increase of dopaminergic innervation in a striatal region associated with speech and language: A comparative analysis of the primate basal ganglia.

    PubMed

    Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R; Wilson, Lakaléa J; Hopkins, William D; Ely, John J; Erwin, Joseph M; Jacobs, Bob; Hof, Patrick R; Sherwood, Chet C

    2016-07-01

    The dopaminergic innervation of the striatum has been implicated in learning processes and in the development of human speech and language. Several lines of evidence suggest that evolutionary changes in dopaminergic afferents of the striatum may be associated with uniquely human cognitive and behavioral abilities, including the association of the human-specific sequence of the FOXP2 gene with decreased dopamine in the dorsomedial striatum of mice. To examine this possibility, we quantified the density of tyrosine hydroxylase-immunoreactive axons as a measure of dopaminergic innervation within five basal ganglia regions in humans, great apes, and New and Old World monkeys. Our results indicate that humans differ from nonhuman primate species in having a significant increase in dopaminergic innervation selectively localized to the medial caudate nucleus. This region of the striatum is highly interconnected, receiving afferents from multiple neocortical regions, and supports behavioral and cognitive flexibility. The medial caudate nucleus also shows hyperactivity in humans lacking a functional FOXP2 allele and exhibits altered dopamine concentrations in humanized Foxp2 mice. Additionally, striatal dopaminergic input was not altered in chimpanzees that used socially learned attention-getting sounds versus those that did not. This evidence indicates that the increase in dopamine innervation of the medial caudate nucleus in humans is a species-typical characteristic not associated with experience-dependent plasticity. The specificity of this increase may be related to the degree of convergence from cortical areas within this region of the striatum and may also be involved in human speech and language. J. Comp. Neurol. 524:2117-2129, 2016. © 2015 Wiley Periodicals, Inc. PMID:26715195

  14. An estuarine species of the alga Vaucheria (Xanthophyceae) displays an increased capacity for turgor regulation when compared to a freshwater species.

    PubMed

    Muralidhar, Abishek; Novis, Phil M; Broady, Paul A; Collings, David A; Garrill, Ashley

    2013-10-01

    Turgor regulation is the process by which walled organisms alter their internal osmotic potential to adapt to osmotic changes in the environment. Apart from a few studies on freshwater oomycetes, the ability of stramenopiles to turgor regulate has not been investigated. In this study, turgor regulation and growth were compared in two species of the stramenopile alga Vaucheria, Vaucheria erythrospora isolated from an estuarine habitat, and Vaucheria repens isolated from a freshwater habitat. Species were identified using their rbcL sequences and respective morphologies. Using a single cell pressure probe to directly measure turgor in Vaucheria after hyperosmotic shock, V. erythrospora was found to recover turgor after a larger shock than V. repens. Threshold shock values for this ability were >0.5 MPa for V. erythrospora and <0.5 MPa for V. repens. Recovery was more rapid in V. erythrospora than V. repens after comparable shocks. Turgor recovery in V. erythrospora was inhibited by Gd(3+) and TEA, suggesting a role for mechanosensitive channels, nonselective cation channels, and K(+) channels in the process. Growth studies showed that V. erythrospora was able to grow over a wider range of NaCl concentrations. These responses may underlie the ability of V. erythrospora to survive in an estuarine habitat and restrict V. repens to freshwater. The fact that both species can turgor regulate may indicate a fundamental difference between members of the Stramenopila, as research to date on oomycetes suggests they are unable to turgor regulate.

  15. Carbohydrate Intake in Form of Gel Is Associated With Increased Gastrointestinal Distress but Not With Performance Differences Compared With Liquid Carbohydrate Ingestion During Simulated Long-Distance Triathlon.

    PubMed

    Sareban, Mahdi; Zügel, David; Koehler, Karsten; Hartveg, Paul; Zügel, Martina; Schumann, Uwe; Steinacker, Jürgen Michael; Treff, Gunnar

    2016-04-01

    The ingestion of exogenous carbohydrates (CHO) during prolonged endurance exercise, such as long-distance triathlon, is considered beneficial with regard to performance. However, little is known about whether this performance benefit differs among different forms of CHO administration. To this end, the purpose of our study was to determine the impact of CHO ingestion from a semisolid source (GEL) on measures of performance and gastrointestinal (GI) comfort compared with CHO ingestion from a liquid source (LIQ). Nine well-trained triathletes participated in this randomized crossover study. Each participant completed a 60-min swim, 180-min bike exercise, and a 60-min all-out run in a laboratory environment under 2 conditions, once while receiving 67.2 ± 7.2 g · h-1 (M ± SD) of CHO from GEL and once while receiving 67.8 ± 4.2 g · h-1 of CHO from LIQ. The amount of fluid provided was matched among conditions. Respiratory exchange ratio (RER), blood glucose, and lactate as well as GI discomfort were assessed at regular intervals during the experiment. The distance covered during the final all-out run was not significantly different among participants ingesting GEL (11.81 ± 1.38 km) and LIQ (11.91 ± 1.53 km; p = .89). RER, blood glucose, and lactate did not differ significantly at any time during the experiment. Seven participants reported GI discomfort with GEL, and no athlete reported GI discomfort with LIQ (p = .016). This study suggests that administration of GEL does not alter long-distance triathlon performance when compared with LIQ, but GEL seems to be associated with reduced GI tolerance. Athletes should consider this a potential disadvantage of GEL administration during long-distance triathlon.

  16. Increased epithelial expression of HLA-DQ and HLA-DP molecules in salivary glands from patients with Sjögren's syndrome compared with obstructive sialadenitis.

    PubMed Central

    Thrane, P S; Halstensen, T S; Haanaes, H R; Brandtzaeg, P

    1993-01-01

    Salivary gland specimens from 10 patients with primary Sjögren's syndrome (pSS) were examined by two-colour immunofluorescence with various combinations of monoclonal and polyclonal antibody reagents of the following specificities: human leucocyte antigen (HLA) class I and II (DR, DP and DQ), CD3, CD45 (leucocyte common antigen), various cytokeratins, and factor VIII-related antigen. Tissue specimens from 10 normal glands and 10 glands with obstructive sialadenitis (no known autoimmunity) served as controls. Only some intercalated ducts and scattered acini of the normal major glands expressed HLA class II determinants (< 5% of total epithelial area); the relative proportion of positive elements indicated differential expression (DR > DP > DQ). SS glands contained substantial T cell infiltrates and increased numbers of activated (DR+) T cells; adjacent epithelium showed extensive differential expression of HLA class II determinants (DR > DP > DQ). Glands with obstructive sialadenitis showed similarly increased epithelial expression of HLA-DR but with surprisingly small amounts of concomitant HLA-DP and -DQ expression. Epithelial HLA class II expression probably depends on cytokines as an inductive event, which is not unique for SS but particularly prominent in this disorder. Our results suggest that epithelial expression of HLA-DP or -DQ, rather than -DR, might be a prerequisite for the autoimmune process of SS to develop in genetically susceptible individuals. Images Fig. 2 PMID:8485911

  17. Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

    SciTech Connect

    Nagy, Edit; Caidahl, Kenneth; Franco-Cereceda, Anders; Baeck, Magnus

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. Black-Right-Pointing-Pointer We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. Black-Right-Pointing-Pointer Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. Black-Right-Pointing-Pointer The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. Black-Right-Pointing-Pointer Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C{sub 4} (LTC{sub 4}) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = -0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = -0.498; P = 0.0298) only in tricuspid aortic valves

  18. The aluminum content of bone increases with age, but is not higher in hip fracture cases with and without dementia compared to controls.

    PubMed

    Hellström, Hans-Olov; Mjöberg, Bengt; Mallmin, Hans; Michaëlsson, Karl

    2005-12-01

    Aluminum is considered a potentially toxic metal, and aluminum poisoning may lead to three types of disorders: aluminum-induced bone disease, microcytic anemia and encephalopathy. This is well known in patients with chronic renal failure, but since healthy subjects with normal renal function retain 4% of the aluminum consumed, they are also at risk of long-term low-grade aluminum intoxication. Included in this study were a total of 172 patients (age range 16-98 years) with the aim of examining whether aluminum accumulates in bone with increasing age. Additionally, we aimed to investigate whether the aluminum content of bone differs between controls and hip fracture cases with and without dementia, in particular in those with Alzheimer's disease. During operations for all cases, bone biopsies were taken with an aluminum-free instrument from the trabecular bone. The samples were measured for their content of aluminum using an inductively coupled mass spectrometer. We found an exponential increase in aluminum content of bone with age. The average aluminum values, adjusted for age, were similar in men and women (P=0.46). No significant differences in sex- and age-adjusted mean aluminum values between the controls and the hip fracture cases with (P=0.72) and without (P=0.33) dementia could be detected. The average aluminum concentration among cases with Alzheimer's disease was also similar to the values of hip fracture patients with other types of dementia (P=0.47). Odds ratios of hip fracture for each quartile of aluminum content in bone were also estimated to detect non-linear effects, but we did not find any statistically significant association remaining after age and sex adjustment. Thus, our results indicate that we accumulate aluminum in bone over our life span, but this does not seem to be of major pathogenetic significance for the occurrence of hip fracture or dementia.

  19. Further increased production of free fatty acids by overexpressing a predicted transketolase gene of the pentose phosphate pathway in Aspergillus oryzae faaA disruptant.

    PubMed

    Tamano, Koichi; Miura, Ai

    2016-09-01

    Free fatty acids are useful as source materials for the production of biodiesel fuel and various chemicals such as pharmaceuticals and dietary supplements. Previously, we attained a 9.2-fold increase in free fatty acid productivity by disrupting a predicted acyl-CoA synthetase gene (faaA, AO090011000642) in Aspergillus oryzae. In this study, we achieved further increase in the productivity by overexpressing a predicted transketolase gene of the pentose phosphate pathway in the faaA disruptant. The A. oryzae genome is predicted to have three transketolase genes and overexpression of AO090023000345, one of the three genes, resulted in phenotypic change and further increase (corresponding to an increased production of 0.38 mmol/g dry cell weight) in free fatty acids at 1.4-fold compared to the faaA disruptant. Additionally, the biomass of hyphae increased at 1.2-fold by the overexpression. As a result, free fatty acid production yield per liter of liquid culture increased at 1.7-fold by the overexpression.

  20. The 5XFAD Mouse Model of Alzheimer's Disease Exhibits an Age-Dependent Increase in Anti-Ceramide IgG and Exogenous Administration of Ceramide Further Increases Anti-Ceramide Titers and Amyloid Plaque Burden.

    PubMed

    Dinkins, Michael B; Dasgupta, Somsankar; Wang, Guanghu; Zhu, Gu; He, Qian; Kong, Ji Na; Bieberich, Erhard

    2015-01-01

    We present evidence that 5XFAD Alzheimer's disease model mice develop an age-dependent increase in antibodies against ceramide, suggesting involvement of autoimmunity against ceramide in Alzheimer's disease pathology. To test this, we increased serum anti-ceramide IgG (2-fold) by ceramide administration and analyzed amyloid plaque formation in 5XFAD mice. There were no differences in soluble or total amyloid-β levels. However, females receiving ceramide had increased plaque burden (number, area, and size) compared to controls. Ceramide-treated mice showed an increase of serum exosomes (up to 3-fold using Alix as marker), suggesting that systemic anti-ceramide IgG and exosome levels are correlated with enhanced plaque formation. PMID:25720409

  1. Increasing 3D Supramolecular Order by Decreasing Molecular Order. A Comparative Study of Helical Assemblies of Dendronized Nonchlorinated and Tetrachlorinated Perylene Bisimides.

    PubMed

    Partridge, Benjamin E; Leowanawat, Pawaret; Aqad, Emad; Imam, Mohammad R; Sun, Hao-Jan; Peterca, Mihai; Heiney, Paul A; Graf, Robert; Spiess, Hans W; Zeng, Xiangbing; Ungar, Goran; Percec, Virgil

    2015-04-22

    A nonplanar, twisted, and flexible tetrachlorinated perylene bisimide (Cl4PBI) was functionalized with two AB3 minidendrons containing hydrogenated or semifluorinated dodecyl groups. The hydrogenated dendron was attached to the imide groups of Cl4PBI via m = 0, 1, and 2 methylenic units, whereas the dendron containing semifluorinated groups was attached via m = 3 or a di(ethylene oxide) linker (m = 2EO). The supramolecular structures of these compounds, determined by a combination of differential scanning calorimetry, X-ray diffraction, and solid-state NMR, were compared with those of nonchlorinated planar and rigid PBI reported previously, which demonstrated the thermodynamically controlled formation of 2D periodic arrays at high temperatures and 3D arrays at low temperatures. The molecularly less ordered Cl4PBI containing hydrogenated dendrons self-organize into exclusively 3D crystalline periodic arrays under thermodynamic control for m = 0 and 2, while the more highly molecularly ordered PBI produced less stable and ordered 3D crystals and also 2D assemblies. This induction of a higher degree of 3D order in supramolecular assemblies of the less well-ordered molecular building blocks was unanticipated. The semifluorinated dendronized Cl4PBI with m = 3 formed a 2D columnar hexagonal array under kinetic control, whereas the compound with m = 2EO formed an unusual 2D honeycomb-like hexagonal phase under thermodynamic control. These Cl4PBI compounds provide a new route to stable crystalline assemblies via thermodynamic control at lower temperatures than previously obtained with PBI, thus generating 3D order in an accessible range of temperature of interest for structural analysis and for technological applications. PMID:25830346

  2. Increased expression of CD146 and microvessel density (MVD) in invasive micropapillary carcinoma of the breast: Comparative study with invasive ductal carcinoma-not otherwise specified.

    PubMed

    Li, Weidong; Yang, Dongling; Wang, Shuling; Guo, Xiaojing; Lang, Ronggang; Fan, Yu; Gu, Feng; Zhang, Xinmin; Niu, Yun; Yan, Xiyun; Fu, Li

    2011-12-15

    Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast, and is characterized by a high metastatic potential and an aggressive clinical course. Studies of CD146 expression and function in breast cancer remain scarce. The aim of this study was to evaluate the role of CD146 and microvessel density (MVD) in breast IMPC. CD146 mRNA expression and immunohistochemistry for CD146 and MVD measured by CD31 were assessed in 82 cases of IMPC and 137 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The mRNA level of CD146 in cancer specimens was higher in IMPC than in IDC-NOS. CD146 expression in tumor cells was up-regulated in IMPC as compared with that in IDC-NOS, and was positively correlated with histological grade, ER, PR status, and P53 expression in IMPC and IDC-NOS. CD146 expression in vascular endothelial cells was significantly higher than that in IDC, and was positively correlated with tumor progression in IMPC and IDC-NOS. MVD in IMPC was significantly higher than that in IDC. CD146 expression in tumor cells was positively correlated with that in vascular endothelial cells of IMPC and IDC-NOS. The association of CD146 expression with MVD and its correlation with progression in breast carcinoma indicated that CD146 is a potentially useful prognostic marker for breast cancer. CD146 could be a new drug target in the treatment of breast cancer.

  3. Increased susceptibility to liver injury after hemorrhagic shock in rats chronically fed ethanol: role of nuclear factor-kappa B, interleukin-6, and granulocyte colony-stimulating factor.

    PubMed

    Ono, Masafumi; Yu, Bi; Hardison, Edith G; Mastrangelo, Mary-Ann A; Tweardy, David J

    2004-06-01

    Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is associated with an increased incidence of multiorgan failure (MOF) and death; however, the molecular basis for this increased susceptibility is unknown. We previously demonstrated that production of interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa B), each make essential contributions to organ injury and inflammation in a rodent model of controlled HS, and we proposed in this study to examine the hypothesis that the increased susceptibility to MOF after shock/trauma in the setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B and production of these proinflammatory cytokines. We observed increased HS-induced liver injury 4 h after resuscitation in rats fed the ethanol-containing Lieber-DeCarli liquid diet for 8 weeks compared with rats fed the control liquid diet (3-fold increase in serum alanine aminotransferase [ALT], P = 0.008, and 2-fold increase in focal liver necrosis, P = 0.005). The increased liver injury in the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats. Thus, increased susceptibility to HS-induced liver injury in the setting of chronic ethanol use may be mediated, at least in part, by increased NF-kappa B activation resulting in increased local production of IL-6 and G-CSF and increased infiltration of neutrophils, which can damage liver cells directly and contribute to impaired sinusoidal blood flow.

  4. Increase in ascorbate content of transgenic tobacco plants overexpressing the acerola (Malpighia glabra) phosphomannomutase gene.

    PubMed

    Badejo, Adebanjo A; Eltelib, Hani A; Fukunaga, Kazunari; Fujikawa, Yukichi; Esaka, Muneharu

    2009-02-01

    Phosphomannomutase (PMM; EC 5.4.2.8) catalyzes the interconversion of mannose-6-phosphate to mannose-1-phosphate in the Smirnoff-Wheeler pathway for the biosynthesis of l-ascorbic acid (AsA). We have cloned the PMM cDNA from acerola (Malpighia glabra), a plant containing an enormous amount of AsA. The AsA contents correlate with the PMM gene expression of the ripening fruits and leaves. The PMM activities in the leaves of acerola, tomato and Arabidopsis correlate with their respective AsA contents. Transgenic tobacco plants overexpressing the acerola PMM gene showed about a 2-fold increase in AsA contents compared with the wild type, with a corresponding correlation with the PMM transcript levels and activities.

  5. Limiting youth access to tobacco: comparing the long-term health impacts of increasing cigarette excise taxes and raising the legal smoking age to 21 in the United States.

    PubMed

    Ahmad, Sajjad; Billimek, John

    2007-03-01

    Although many states in the US have raised cigarette excise taxes in recent years, the size of these increases have been fairly modest (resulting in a 15% increase in the per pack purchase price), and their impact on adult smoking prevalence is likely insufficient to meet Healthy People 2010 objectives. This paper presents the results of a 75-year dynamic simulation model comparing the long-term health benefits to society of various levels of tax increase to a viable alternative: limiting youth access to cigarettes by raising the legal purchase age to 21. If youth smoking initiation is delayed as assumed in the model, increasing the smoking age would have a minimal immediate effect on adult smoking prevalence and population health, but would affect a large drop in youth smoking prevalence from 22% to under 9% for the 15-17-year-old age group in 7 years (by 2010)-better than the result of raising taxes to increase the purchase price of cigarettes by 100%. Reducing youth initiation by enforcing a higher smoking age would reduce adult smoking prevalence in the long-term (75 years in the future) to 13.6% (comparable to a 40% tax-induced price increase), and would produce a cumulative gain of 109 million QALYs (comparable to a 20% price increase). If the political climate continues to favor only moderate cigarette excise tax increases, raising the smoking age should be considered to reduce the health burden of smoking on society. The health benefits of large tax increases, however, would be greater and would accrue faster than raising the minimum legal purchase age for cigarettes.

  6. C57BL/KsJ-db/db-ApcMin/+ Mice Exhibit an Increased Incidence of Intestinal Neoplasms

    PubMed Central

    Hata, Kazuya; Kubota, Masaya; Shimizu, Masahito; Moriwaki, Hisataka; Kuno, Toshiya; Tanaka, Takuji; Hara, Akira; Hirose, Yoshinobu

    2011-01-01

    The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-ApcMin/+ (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-ApcMin/+ (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db- Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients. PMID:22174655

  7. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    PubMed

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

  8. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    PubMed

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects. PMID:21272402

  9. A comparative evaluation of the increase in root canal surface area and canal transportation in curved root canals by three rotary systems: A cone-beam computed tomographic study

    PubMed Central

    Prasanthi, Nalam NVD; Rambabu, Tanikonda; Sajjan, Girija S; Varma, K Madhu; Satish, R Kalyan; Padmaja, M

    2016-01-01

    Aim: The aim of this study was to measure the increase in root canal surface area and canal transportation after biomechanical preparation at 1, 3, and 5 mm short of the apex with three different rotary systems in both continuous rotary and reciprocating rotary motions. Materials and Methods: Sixty freshly extracted human mandibular molars with mesial root canal curvatures between 20° and 30° were included in the study. Teeth were randomly distributed into three groups (n = 20). Biomechanical preparations were done in all the mesial canals. In Group 1, instrumentation was done with ProTaper universal rotary files, Group 2, with K3XF rotary files, and Group 3, with LSX rotary files. Each group was further subdivided into subgroups A and B (n = 10) where instrumentation was done by continuous rotary and reciprocating rotary techniques, respectively. Increase in root canal surface area and canal transportation was measured using the preoperative and postoperative cone-beam computed tomography scans. Statistical Analysis: The data were analyzed by one-way ANOVA followed by Tukey pairwise multiple comparison tests. Results: Increase in root canal surface area was significantly more (P < 0.05) in ProTaper and K3XF groups when compared to LSX group. Canal transportation was significantly more (P < 0.05) in ProTaper group when compared to K3XF and LSX groups. There was no significant difference (P > 0.05) in increase of root canal surface area and canal transportation between continuous rotary and reciprocating rotary techniques for ProTaper Universal, K3XF and LSX groups. Conclusion: LSX rotary system showed minimal increase of root canal surface area and minimal canal transportation when compared to ProTaper and K3XF rotary systems.

  10. A comparative evaluation of the increase in root canal surface area and canal transportation in curved root canals by three rotary systems: A cone-beam computed tomographic study

    PubMed Central

    Prasanthi, Nalam NVD; Rambabu, Tanikonda; Sajjan, Girija S; Varma, K Madhu; Satish, R Kalyan; Padmaja, M

    2016-01-01

    Aim: The aim of this study was to measure the increase in root canal surface area and canal transportation after biomechanical preparation at 1, 3, and 5 mm short of the apex with three different rotary systems in both continuous rotary and reciprocating rotary motions. Materials and Methods: Sixty freshly extracted human mandibular molars with mesial root canal curvatures between 20° and 30° were included in the study. Teeth were randomly distributed into three groups (n = 20). Biomechanical preparations were done in all the mesial canals. In Group 1, instrumentation was done with ProTaper universal rotary files, Group 2, with K3XF rotary files, and Group 3, with LSX rotary files. Each group was further subdivided into subgroups A and B (n = 10) where instrumentation was done by continuous rotary and reciprocating rotary techniques, respectively. Increase in root canal surface area and canal transportation was measured using the preoperative and postoperative cone-beam computed tomography scans. Statistical Analysis: The data were analyzed by one-way ANOVA followed by Tukey pairwise multiple comparison tests. Results: Increase in root canal surface area was significantly more (P < 0.05) in ProTaper and K3XF groups when compared to LSX group. Canal transportation was significantly more (P < 0.05) in ProTaper group when compared to K3XF and LSX groups. There was no significant difference (P > 0.05) in increase of root canal surface area and canal transportation between continuous rotary and reciprocating rotary techniques for ProTaper Universal, K3XF and LSX groups. Conclusion: LSX rotary system showed minimal increase of root canal surface area and minimal canal transportation when compared to ProTaper and K3XF rotary systems. PMID:27656062

  11. Increased Risk of Locoregional Recurrence for Women With T1-2N0 Triple-Negative Breast Cancer Treated With Modified Radical Mastectomy Without Adjuvant Radiation Therapy Compared With Breast-Conserving Therapy

    PubMed Central

    Abdulkarim, Bassam S.; Cuartero, Julie; Hanson, John; Deschênes, Jean; Lesniak, David; Sabri, Siham

    2011-01-01

    Purpose To evaluate the risk of locoregional recurrence (LRR) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (triple-negative breast cancer [TNBC]). Patients and Methods Patients diagnosed with TNBC were identified from a cancer registry in a single institution (n=768). LRR-free survival was estimated using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to determine risk of LRR on the basis of locoregional management: breast-conserving therapy (BCT; ie, lumpectomy and adjuvant radiation therapy [RT]) and modified radical mastectomy (MRM) in the TNBC population and T1-2N0 subgroup. Results At a median follow-up of 7.2 years, 77 patients (10%) with TNBC developed LRR. Five-year LRR-free survival was 94%, 85%, and 87% in the BCT, MRM, and MRM + RT groups, respectively (P < .001). In multivariate analysis, MRM (compared with BCT), lymphovascular invasion and lymph node positivity were associated with increased LRR. Conversely, adjuvant chemotherapy was associated with decreased risk of LRR. For patients with T1-2N0 tumors, 5-year LRR-free survival was 96% and 90% in the BCT and MRM groups, respectively (P =.027), and MRM was the only independent prognostic factor associated with increased LRR compared with BCT (hazard ratio, 2.53; 95% CI, 1.12 to 5.75; P= .0264). Conclusion Women with T1-2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT. Prospective studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC. PMID:21670451

  12. Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice.

    PubMed

    Merkel, M; Velez-Carrasco, W; Hudgins, L C; Breslow, J L

    2001-11-01

    Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway. PMID:11606787

  13. Microbial phytase addition resulted in a greater increase in phosphorus digestibility in dry-fed compared with liquid-fed non-heat-treated wheat-barley-maize diets for pigs.

    PubMed

    Blaabjerg, K; Thomassen, A-M; Poulsen, H D

    2015-02-01

    The objective was to evaluate the effect of microbial phytase (1250 FTU/kg diet with 88% dry matter (DM)) on apparent total tract digestibility (ATTD) of phosphorus (P) in pigs fed a dry or soaked diet. Twenty-four pigs (65±3 kg) from six litters were used. Pigs were housed in metabolism crates and fed one of four diets for 12 days; 5 days for adaptation and 7 days for total, but separate collection of feces and urine. The basal diet was composed of wheat, barley, maize, soybean meal and no mineral phosphate. Dietary treatments were: basal dry-fed diet (BDD), BDD with microbial phytase (BDD+phy), BDD soaked for 24 h at 20°C before feeding (BDS) and BDS with microbial phytase (BDS+phy). Supplementation of microbial phytase increased ATTD of DM and crude protein (N×6.25) by 2 and 3 percentage units (P<0.0001; P<0.001), respectively. The ATTD of P was affected by the interaction between microbial phytase and soaking (P=0.02). This was due to a greater increase in ATTD of P by soaking of the diet containing solely plant phytase compared with the diet supplemented with microbial phytase: 35%, 65%, 44% and 68% for BDD, BDD+phy, BSD and BSD+phy, respectively. As such, supplementation of microbial phytase increased ATTD of P in the dry-fed diet, but not in the soaked diet. The higher ATTD of P for BDS compared with BDD resulted from the degradation of 54% of the phytate in BDS by wheat and barley phytases during soaking. On the other hand, soaking of BDS+phy did not increase ATTD of P significantly compared with BDD+phy despite that 76% of the phytate in BDS+phy was degraded before feeding. In conclusion, soaking of BDS containing solely plant phytase provided a great potential for increasing ATTD of P. However, this potential was not present when microbial phytase (1250 FTU/kg diet) was supplemented, most likely because soaking of BDS+phy for 24 h at 20°C did not result in a complete degradation of phytate before feeding.

  14. Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.

    PubMed

    Chang, Tammy T; Spurlock, Sandra M; Candelario, Tara Lynne T; Grenon, S Marlene; Hughes-Fulford, Millie

    2015-10-01

    The health risks of a dysregulated immune response during spaceflight are important to understand as plans emerge for humans to embark on long-term space travel to Mars. In this first-of-its-kind study, we used adoptive transfer of T-cell receptor transgenic OT-II CD4 T cells to track an in vivo antigen-specific immune response that was induced during the course of spaceflight. Experimental mice destined for spaceflight and mice that remained on the ground received transferred OT-II cells and cognate peptide stimulation with ovalbumin (OVA) 323-339 plus the inflammatory adjuvant, monophosphoryl lipid A. Control mice in both flight and ground cohorts received monophosphoryl lipid A alone without additional OVA stimulation. Numbers of OT-II cells in flight mice treated with OVA were significantly increased by 2-fold compared with ground mice treated with OVA, suggesting that tolerance induction was impaired by spaceflight. Production of proinflammatory cytokines were significantly increased in flight compared with ground mice, including a 5-fold increase in IFN-γ and a 10-fold increase in IL-17. This study is the first to show that immune tolerance may be impaired in spaceflight, leading to excessive inflammatory responses.

  15. Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current.

    PubMed

    Best, Tyler K; Siarey, Richard J; Galdzicki, Zygmunt

    2007-01-01

    Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase ( approximately 2-fold) in GABA(B)-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABA(B) receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

  16. Age-related arterial telomere uncapping and senescence is greater in women compared with men.

    PubMed

    Walker, Ashley E; Morgan, R Garrett; Ives, Stephen J; Cawthon, Richard M; Andtbacka, Robert H I; Noyes, Dirk; Lesniewski, Lisa A; Richardson, Russell S; Donato, Anthony J

    2016-01-01

    Telomere uncapping increases with advancing age in human arteries and this telomere uncapping is associated with increased markers of senescence, independent of mean telomere length. However, whether there are sex specific differences in arterial telomere uncapping is unknown. We found that telomere uncapping (serine 139 phosphorylated histone γ-H2A.X in telomeres) in arteries was ~2.5 fold greater in post-menopausal women (n=17, 63±2 years) compared with pre-menopausal women (n=11, 30±2 years, p=0.02), while there was only a trend towards greater telomere uncapping in older men (n=26, 66±2 years) compared with young men (n=11, 31±2, p=0.11). Senescence markers, p53 bound to the p21 gene promoter and p21 gene expression, were 3-4 fold greater in post-menopausal compared with pre-menopausal women (p=0.01-0.02), but only 1.5-2 fold greater in older compared with young men (p=0.02-0.08). Blood glucose was related to telomere uncapping in women, while systolic blood pressure, pulse pressure and serum creatinine were related to telomere uncapping in men. Mean arterial telomere length decreased similarly in women and men with age (p<0.01). Thus, the age-related increase in arterial telomere uncapping and senescence is greater in women than men, despite similar age-related reductions in mean telomere length in both sexes.

  17. Increasing discordant antioxidant protein levels and enzymatic activities contribute to increasing redox imbalance observed during human prostate cancer progression

    PubMed Central

    Chaiswing, Luksana; Zhong, Weixiong; Oberley, Terry D.

    2014-01-01

    A metabolomics study demonstrated a decrease in glutathione and an increase in cysteine (Cys) levels in human prostate cancer (PCa) tissues as Gleason scores increased, indicating redox imbalance with PCa progression. These results were extended in the present study by analyzing redox state of the protein thioredoxin 1 (Trx1) and sulfinylation (SO3) of peroxiredoxins (Prxs) (PrxsSO3) in PCa tissues and cell lines. Lysates of paired human PCa tissues with varying degree of aggressiveness and adjacent benign (BN) tissues were used for analysis. Redox western blot analysis of Trx1 demonstrated low levels of reduced and high levels of oxidized Trx1 (functional and non-functional, respectively) in high grade PCa (Gleason scores 4+4 to 4+5) in comparison to intermediate grade PCa (Gleason scores 3+3 to 3+4) or BN tissues. PrxsSO3 were increased in high grade PCa. Oxidized Trx1 and PrxsSO3 are indicators of oxidative stress. To study whether redox imbalance may potentially affect enzyme activities of antioxidant proteins (AP), we determined levels of selected AP in PCa tissues by western blot analysis and found that mitochondrial manganese superoxide dismutase (MnSOD), Prx 3, and Trx1 were increased in high grade PCa tissues when compared with BN tissues. Enzyme activities of MnSOD in high grade PCa tissues were significantly increased but at a lower magnitude when compared with the levels of MnSOD protein (0.5 folds vs. 2 folds increase). Trx1 activity was not changed in high grade PCa tissues despite a large increase in Trx1 protein expression. Further studies demonstrated a significant increase in posttranslational modifications of tyrosine and lysine residues in MnSOD protein and oxidation of Cys at active site (Cys 32 and Cys 35) and regulatory site (Cys 62 and Cys 69) of Trx1 in high grade PCa compared to BN tissues. These discordant changes between protein levels and enzyme activities are consistent with protein inactivation by redox imbalance and

  18. Landslides induced by heavy rainfall in July 2012 in Northern Kyushu District, Japan and the influence of long term rainfall increase comparing with the slope destabilization due to strong seismic shaking

    NASA Astrophysics Data System (ADS)

    Kubota, Tetsuya; Shinohara, Yoshinori; Aditian, Aril

    2013-04-01

    1. Objective We had a deluge in July 2012 in the northern Kyushu district with intense rainfall of 800mm and 108mm/hr. This intensity yielded countless traces of debris flow and landslides, slope failures that induced tremendous damage and causalities in the area. Hence, several field investigations and reconnaissance tasks were conducted to delve into this sediment-related disaster. The various results and the information obtained through this investigation were reported, mentioning the damage, the meteorological condition, geologic-geomorphologic features and hydraulic characteristics of the debris flows, vegetation effects, and the influence of the climate change. Increase in rainfall that may be induced by the global climate change is obvious in Kyushu district, Japan, according to the analysis of rain data observed in various locations including mountainside points that are not influenced by local warming due to urbanization. On this point of view, we are intrigued to elucidate the response of landslide to this increase in rainfall. Hence, its long term impact on this landslide disaster is also analyzed comparing with the slope destabilization due to strong seismic shaking. 2. Method and target areas Field investigation on landslides slopes, slope failures and torrents where debris flows occurred are conducted to obtain the geologic data, geo-structure, vegetation feature, soil samples and topographic data i.e. cross sections, then soil shear tests and soil permeability tests are also conducted. The rainfall data at the nearest rain observatory were obtained from the database of Japan meteorological agency. The long term impact on the slope stability at some slopes in the area is analyzed by the finite element method (FEM) combined with rain infiltration and seepage analysis with the long term rainfall fluctuation data, obtaining factor of safety ( Fs) on real landslide slopes. The results are compared with the destabilized influence on the slopes due to the

  19. [Increase in skin blood circulation and transcutaneous oxygen partial pressure of the top of the foot in lower leg immersion in water containing carbon dioxide in patients with arterial occlusive disease. Results of a controlled study compared with fresh water].

    PubMed

    Hartmann, B; Drews, B; Burnus, C; Bassenge, E

    1991-01-01

    Semi-quantitative Doppler laser flowmetry and measurement of transcutaneous oxygen partial pressure (TCPO2 in mmHg) are reliable, non-invasive methods of continuous measurement suitable for underwater use. We measured the effect of aqueous CO2 (succinate + sodium bicarbonate = Kao Bub; 1400 mg CO2 per kg water) compared with fresh water (both at 34 degrees C, depth of leg immersion 35 cm, immersion time 20 min) on circulation and TCPO2 in the feet of 15 patients with bilateral stage-II occlusion of the Aa. fem. superf. intraindividually in a randomised, crossover trial. Measurements were made at the same time of day on two consecutive days. No change in either cutaneous microcirculation or TCPO2 was observed during immersion in fresh water. During immersion in a CO2 bath both culaneous blood flow (as expressed by Doppler laser flux) and the amplitude of the Doppler laser vasomotion flux increased more than threefold (p less than 0.001, Wilcoxon), while sitting TCPO2 increased by over 10% (from 63 to 71 mmHg; p less than 0.001). The observed changes in oxygen dissociation and cutaneous microcirculation may help to provide an explanation for the well-known therapeutic effect of CO2 baths in all stages of occlusive arterial disease. PMID:1776351

  20. Increasing The Number of Embryos Transferred from Two to Three, Does not Increase Pregnancy Rates in Good Prognosis Patients

    PubMed Central

    Ashrafi, Mahnaz; Madani, Tahereh; Movahedi, Mina; Arabipoor, Arezoo; Karimian, Leili; Mirzaagha, Elaheh; Chehrazi, Mohammad

    2015-01-01

    Background To compare the pregnancy outcomes after two embryos versus three embryos transfers (ETs) in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Materials and Methods This retrospective study was performed on three hundred eighty seven women with primary infertility and with at least one fresh embryo in good quality in order to transfer at each IVF/ICSI cycle, from September 2006 to June 2010. Patients were categorized into two groups according to the number of ET as follows: ET2 and ET3 groups, indicating two and three embryos were respectively transferred. Pregnancy outcomes were compared between ET2 and ET3 groups. Chi square and student t tests were used for data analysis. Results Clinical pregnancy and live birth rates were similar between two groups. The rates of multiple pregnancies were 27 and 45.2% in ET2 and ET3 groups, respectively. The rate of multiple pregnancies in young women was significantly increased when triple instead of double embryos were transferred. Logistic regression analysis indicated two significant prognostic variables for live birth that included number and quality of transferred embryos; it means that the chance of live birth following ICSI treatment increased 3.2-fold when the embryo with top quality (grade A) was transferred, but the number of ET had an inverse relationship with live birth rate; it means that probability of live birth in women with transfer of two embryos was three times greater than those who had three ET. Conclusion Due to the difficulty of implementation of the elective single-ET technique in some infertility centers in the world, we suggest transfer of double instead of triple embryos when at least one good quality embryo is available for transfer in women aged 39 years or younger. However, to reduce the rate of multiple pregnancies, it is recommended to consider the elective single ET strategy. PMID:26644851

  1. Comorbidity increases the risk of hospitalizations in multiple sclerosis

    PubMed Central

    Elliott, Lawrence; Marriott, James; Cossoy, Michael; Tennakoon, Aruni; Yu, Nancy

    2015-01-01

    Objective: We aimed to evaluate the association between comorbidity and rates of hospitalization in the multiple sclerosis (MS) population as compared to a matched cohort from the general population. Methods: Using population-based administrative data from the Canadian province of Manitoba, we identified 4,875 persons with MS and a matched general population cohort of 24,533 persons. We identified all acute care hospitalizations in the period 2007–2011. Using general linear models, we evaluated the association between comorbidity status and hospitalization rates (all-cause, non-MS-related, MS-related) in the 2 populations, adjusting for age, sex, and socioeconomic status. Results: Comorbidity was common in both cohorts. Over the 5-year study period, the MS population had a 1.5-fold higher hospitalization rate (adjusted rate ratio [aRR] 1.56; 95% confidence interval [CI] 1.44–1.68) than the matched population. Any comorbidity was associated with a 2-fold increased risk of non-MS-related hospitalization rates (aRR 2.21; 95% CI 1.73–2.82) in the MS population, but a nearly 4-fold increase in hospitalization rates in the matched population (aRR 3.85; 95% CI 3.40–4.35). Comorbidity was not associated with rates of hospitalization for MS-related reasons, regardless of how comorbidity status was defined. Conclusions: In the MS population, comorbidity is associated with an increased risk of all-cause hospitalizations, suggesting that the prevention and management of comorbidity may reduce hospitalizations. PMID:25540309

  2. Increased heterosis in selfing populations of a perennial forb

    PubMed Central

    Oakley, Christopher G.; Spoelhof, Jonathan P.; Schemske, Douglas W.

    2015-01-01

    Quantifying the importance of random genetic drift in natural populations is central to understanding the potential limits to natural selection. One approach is to estimate the magnitude of heterosis, the increased fitness of progeny derived from crosses between populations relative to crosses within populations caused by the heterozygous masking of deleterious recessive or nearly recessive alleles that have been fixed by drift within populations. Self-fertilization is expected to reduce the effective population size by half relative to outcrossing, and population bottlenecks may be common during the transition to selfing. Therefore, chance fixation of deleterious alleles due to drift in selfing populations should increase heterosis between populations. Increased homozygosity due to fixation or loss of alleles should also decrease inbreeding depression within populations. Most populations of the perennial herb Arabidopsis lyrata ssp. lyrata are self-incompatible (SI), but several have evolved self-compatibility and are highly selfing. We quantified heterosis and inbreeding depression in two predominantly self-compatible (SC) and seven SI populations in a field common garden experiment within the species' native range and examined the correlation between these metrics to gauge the similarity in their genetic basis. We measured proportion germination in the lab, and survival and fecundity (flower and seed production) for 2 years in the field, and calculated estimates of cumulative fitness. We found 7.2-fold greater heterosis in SC compared with SI populations, despite substantial heterosis in SI populations (56 %). Inbreeding depression was >61 %, and not significantly different between SC and SI populations. There was no correlation between population estimates of heterosis and inbreeding depression, suggesting that they have somewhat different genetic bases. Combined with other sources of information, our results suggest a history of bottlenecks in all of these

  3. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

    PubMed Central

    Brown, D. M.; Williams, H.; Ryan, K. J. P.; Wilson, T. L.; Daniel, Z. C. T. R.; Mareko, M. H. D.; Emes, R. D.; Harris, D. W.; Jones, S.; Wattis, J. A. D.; Dryden, I. L.; Hodgman, T. C.; Brameld, J. M.; Parr, T.

    2016-01-01

    We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth. PMID:27350173

  4. Increasing Partner Attendance in Antenatal Care and HIV Testing Services: Comparable Outcomes Using Written versus Verbal Invitations in an Urban Facility-Based Controlled Intervention Trial in Mbeya, Tanzania

    PubMed Central

    Theuring, Stefanie; Jefferys, Laura F.; Nchimbi, Philo; Mbezi, Paulina; Sewangi, Julius

    2016-01-01

    In many Sub-Saharan African settings male partner involvement in antenatal care (ANC) remains low, although great benefits for maternal and infant health outcomes have been long recognised, in particular regarding the prevention of HIV transmission. Yet there is paucity on evidence regarding the effectiveness of strategies to increase male partner involvement. This controlled intervention trial in Ruanda Health Centre in Mbeya, Tanzania, assessed the effectiveness of invitation letters for male involvement in ANC. Pregnant women approaching ANC without partners received official letters inviting the partner to attend ANC. A control group was instructed to verbally invite partners. Partner attendance was recorded at two subsequent ANC visits. Rates for male partner return, couple voluntary counselling and testing (CVCT), and influencing factors were analysed. From 199 ANC clients in total, 97 were assigned to the invitation letter group; 30 of these (30.9%) returned with their male partners for ANC. In the control group of 102 women, 28 (27.5%) returned with their partner. In both groups CVCT rates among jointly returning couples were 100%. Partner return/CVCT rate was not statistically different in intervention and control group (OR 1.2, p = 0.59). Former partner attendance at ANC during a previous pregnancy was the only factor found to be significantly linked with partner return (p = 0.03). Our study demonstrates that rather simple measures to increase male partner attendance in ANC and CVCT can be effective, with written and verbal invitations having comparable outcomes. In terms of practicability in Sub-Saharan African settings, we recommend systematic coaching of ANC clients on how to verbally invite male partners in the first instance, followed by written invitation letters for partners in case of their non-attendance. Further studies covering both urban and rural settings will be more informative for effective translation into policy. PMID:27043707

  5. Spironolactone and colitis: Increased mortality in rodents and in humans

    PubMed Central

    Johnson, Laura A.; Govani, Shail M.; Joyce, Joel C.; Waljee, Akbar K.; Gillespie, Brenda W.; Higgins, Peter D. R.

    2011-01-01

    Background and Methods Crohn’s disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an anti-fibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is anti-fibrotic in the context of intestinal inflammation. In vitro, spironolactone repressed fibrogenesis in TGFβ-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since IBD patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n=390 deaths, p<0.0001). In patients without liver disease, the adjusted OR for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% CI: 1.51 – 2.63) In contrast to the main effect of spironolactone mortality, multivariable modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted odds ratio for mortality after CDI was 1.96 (95% CI: 1.50 – 2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82 – 2.00) for patients with liver disease on spironolactone, when compared to a reference group without liver disease or spironolactone use. Conclusions We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the US. PMID:22081497

  6. An energy-reduced dietary pattern, including moderate protein and increased nonfat dairy intake combined with walking promotes beneficial body composition and metabolic changes in women with excess adiposity: a randomized comparative trial

    PubMed Central

    Shlisky, Julie D; Durward, Carrie M; Zack, Melissa K; Gugger, Carolyn K; Campbell, Jessica K; Nickols-Richardson, Sharon M

    2015-01-01

    Moderate protein and nonfat dairy intake within an energy-reduced diet (ERD) may contribute to health benefits achieved with body weight (BW) loss. The current study examined the effectiveness of a weight-loss/weight-loss maintenance intervention using an ERD with moderate dietary protein (30% of kcals) and increased nonfat dairy intake (4–5 svg/d), including yogurt (INT group) and daily walking compared to an ERD with standard protein (16–17% of kcals) and standard nonfat dairy intake (3 svg/d) (COM group) with daily walking. A randomized comparative trial with 104 healthy premenopausal women with overweight/obesity was conducted in a university setting. Women were randomized to INT group or COM group. Anthropometric measurements, as well as dietary intake, selected vital signs, resting energy expenditure, blood lipids, glucose, insulin, and selected adipose-derived hormones were measured at baseline, and weeks 2, 12, and 24. Targets for dietary protein and nonfat dairy intake, while initially achieved, were not sustained in the INT group. There were no significant effects of diet group on anthropometric measurements. Women in the INT group and COM group, respectively, reduced BW (−4.9 ± 3.2 and −4.3 ± 3.3 kg, P < 0.001) and fat mass (−3.0 ± 2.2 and −2.3 ± 2.3 kg, P < 0.001) during the 12-week weight-loss phase and maintained these losses at 24 weeks. Both groups experienced significant decreases in body mass index, fat-free soft tissue mass, body fat percentage, waist and hip circumferences and serum triglycerides, total cholesterol, and leptin (all P < 0.001). Healthy premenopausal women with excess adiposity effectively lost BW and fat mass and improved some metabolic risk factors following an ERD with approximately 20% protein and 3 svg/d of nonfat dairy intake. PMID:26405524

  7. Increased hepatic functionality of the human hepatoma cell line HepaRG cultured in the AMC bioreactor.

    PubMed

    Nibourg, Geert A A; Hoekstra, Ruurdtje; van der Hoeven, Tessa V; Ackermans, Mariëtte T; Hakvoort, Theodorus B M; van Gulik, Thomas M; Chamuleau, Robert A F M

    2013-08-01

    The clinical application of a bioartificial liver (BAL) depends on the availability of a human cell source with high hepatic functionality, such as the human hepatoma cell line HepaRG. This cell line has demonstrated high hepatic functionality, but the effect of BAL culture on its functionality in time is not known. Therefore, we studied the characteristics of the HepaRG-AMC-BAL over time, and compared the functionality of the HepaRG-AMC-BAL with monolayer cultures of HepaRG cells, normalized for protein (bioactive mass) and DNA (cell number). Histological analysis of 14-day-old BALs demonstrated functional heterogeneity similar to that of monolayer cultures. Hepatic functionality of the HepaRG-AMC-BALs increased during 2-3 weeks of culture. The majority of the measured protein-normalized hepatic functions were already higher in day 14 BAL cultures compared to monolayer cultures, including ammonia elimination (3.2-fold), urea production (1.5-fold), conversion of (15)N-ammonia into (15)N-urea (1.4-fold), and cytochrome P450 3A4 activity (7.9-fold). Lactate production in monolayer cultures switched into lactate consumption in the BAL cultures, a hallmark of primary hepatocytes. When normalized for DNA, only cytochrome P450 3A4 activity was 2.5-fold higher in the BAL cultures compared to monolayer cultures and lactate production switched to consumption, whereas urea production and (15)N-urea production were 1.5- to 2-fold lower. The different outcomes for protein and DNA normalized functions probably relate to a smaller cell volume of HepaRG cells when cultured in the AMC-BAL. Cell damage was 4-fold lower in day 14 BAL cultures compared to monolayer cultures. Transcript levels of cytochrome P450 1A2, 2B6, 3A4 and 3A7 genes and of regulatory genes hepatic nuclear factor 4α and pregnane X receptor increased in time in BAL cultures and reached higher levels than in monolayer cultures. Lastly, metabolism of amino acids, particularly the alanine consumption and ornithine

  8. Ectopic expression of anthocyanin 5-o-glucosyltransferase in potato tuber causes increased resistance to bacteria.

    PubMed

    Lorenc-Kukuła, Katarzyna; Jafra, Sylwia; Oszmiański, Jan; Szopa, Jan

    2005-01-26

    The principal goal of this paper was to investigate the significance of anthocyanin 5-O-glucosyltransferase (5-UGT) for potato tuber metabolism. The ectopic expression of a 5-UGT cDNA in the tuber improved the plant's defense against pathogen infection. The resistance of transgenic lines against Erwinia carotovora subsp. carotovora was about 2-fold higher than for nontransformed plants. In most cases the pathogen resistance was accompanied by a significant increase in tuber yield. To investigate the molecular basis of transgenic potato resistance, metabolic profiling of the plant was performed. In tuber extracts, the anthocyanin 3,5-O-substituted level was significantly increased when compared to that of the control plant. Of six anthocyanin compounds identified, the highest quantity for pelargonidin 3-rutinoside-5-glucoside acylated with p-coumaric acid and peonidin 3-rutinoside-5-glucoside acylated with p-coumaric acid was detected. A significant increase in starch and a decrease in sucrose level in transgenic tubers have been detected. The level of all other metabolites (amino acids, organic acids, polyamines, and fatty acids) was quite the same as in nontransformants. The plant resistance to bacterial infection correlates with anthocyanin content and sucrose level. The properties of recombinant glucosyltransferase were analyzed in in vitro experiments. The enzyme kinetics and its biochemical properties were similar to those from other sources.

  9. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

    PubMed Central

    Shinn, Helen Ki; Yan, Chunri; Kim, Tae-Hwan; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Moon, Sung-Kwon; Kim, Nam-Hyung; Kim, Jayoung; Cha, Eun-Jong

    2016-01-01

    Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections. PMID:27377944

  10. An energy-dense complementary food is associated with a modest increase in weight gain when compared with a fortified porridge in Malawian children aged 6-18 months.

    PubMed

    Lin, Carol A; Manary, Mark J; Maleta, Ken; Briend, André; Ashorn, Per

    2008-03-01

    Poor complementary feeding practices are associated with stunting and growth faltering throughout the developing world. The objective was to compare the effect of using peanut-/soy-based fortified spread (FS) and corn porridge fortified with fish powder (FP) as complementary foods on growth in rural Malawian children. A total of 240 children were enrolled at the age of 6 mo and randomized to receive FS or FP. Both complementary foods provided 836 kJ/d from 6 to 9 mo of age and 1254 kJ/d from 9 to 18 mo of age. Children were followed monthly for anthropometry and fortnightly for the symptoms of fever, cough, or diarrhea until they were 18 mo old. Zn and Se status were assessed at 6 and 12 mo. The primary outcomes were the rates of weight and length gain from 6-12 mo and from 12-18 mo. Children who received FS gained 110 g more (95% CI 220 to 10) from 6-12 mo of age than children receiving FP. Weight gain did not differ between children receiving FS and FP between 12 and 18 mo of age, nor did statural growth from 6 to 12 mo or 12 to 18 mo. A total of 23% of all children were Zn deficient at 6 mo of age and this increased to 37% at 12 mo of age. Neither FS nor FP was associated with significantly improved Zn status. FS was associated with better weight gain from 6-12 mo of age and may be useful in conjunction with additional interventions to improve infant growth in the developing world.

  11. The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the proimmune effects of MenB OMVs on human macrophages, compared with NadA- OMVs, without further stimulating their proinflammatory activity on circulating monocytes.

    PubMed

    Tavano, Regina; Franzoso, Susanna; Cecchini, Paola; Cartocci, Elena; Oriente, Francesca; Aricò, Beatrice; Papini, Emanuele

    2009-07-01

    Hypervirulent MenB causing fatal human infections frequently display the oligomeric-coiled coil adhesin NadA, a 45-kDa intrinsic outer membrane protein implicated in binding to and invasion of respiratory epithelial cells. A recombinant soluble mutant lacking the 10-kDa COOH terminal membrane domain (NadA(Delta351-405)) also activates human monocytes/macrophages/DCs. As NadA is physiologically released during sepsis as part of OMVs, in this study, we tested the hypothesis that NadA(+) OMVs have an enhanced or modified proinflammatory/proimmune action compared with NadA(-) OMVs. To do this we investigated the activity of purified free NadA(Delta351-405) and of OMVs from MenB and Escherichia coli strains, expressing or not full-length NadA. NadA(Delta351-405) stimulated monocytes and macrophages to secrete cytokines (IL-1beta, TNF-alpha, IL-6, IL-12p40, IL-12p70, IL-10) and chemokines (IL-8, MIP-1alpha, MCP-1, RANTES), and full-length NadA improved MenB OMV activity, preferentially on macrophages, and only increased cytokine release. NadA(Delta351-405) induced the lymphocyte costimulant CD80 in monocytes and macrophages, and NadA(+) OMVs induced a wider set of molecules supporting antigen presentation (CD80, CD86, HLA-DR, and ICAM-1) more efficiently than NadA(-) OMVs only in macrophages. Moreover, membrane NadA effects, unlike NadA(Delta351-405) ones, were much less IFN-gamma-sensitive. The activity of NadA-positive E. coli OMVs was similar to that of control OMVs. NadA in MenB OMVs acted at adhesin concentrations approximately 10(6) times lower than those required to stimulate cells with free NadA(Delta351-405).

  12. Aldosterone increases the apical Na sup + permeability of toad bladder by two different mechanisms

    SciTech Connect

    Asher, C.; Garty, H. )

    1988-10-01

    The aldosterone-induced augmentation of Na{sup +} transport in toad bladder was analyzed by comparing the hormonal actions on the transepithelial short-circuit current and on the amiloride-sensitive {sup 22}Na{sup +} uptake in isolated membrane vesicles. Incubating bladders with 0.5 {mu}M aldosterone for 3 hr evoked more than a 2-fold increase of the short-circuit current but had no effect on the amiloride-sensitive Na{sup +} transport in apical vesicles derived from the treated tissue. A longer incubation produced an additional augmentation of the short-circuit current, which was accompanied by about a 3-fold increase of the channel activity in isolated membranes. The stimulatory effect of aldosterone sustained in vesicles was inhibited by the antagonist spironolactone and the protein synthesis inhibitor cycloheximide. It is suggested that aldosterone elevates the apical Na{sup +} permeability of target epithelia by two different mechanisms: a relatively fast effect which is insensitive to triiodothyronine or butyrate and is not sustained by the isolated membrane, and a slower or later response blocked by these reagents, which is preserved by the isolated membrane. The data also indicate that these processes are mediated by different nuclear receptors.

  13. Wood Formation in Trees Is Increased by Manipulating PXY-Regulated Cell Division.

    PubMed

    Etchells, J Peter; Mishra, Laxmi S; Kumar, Manoj; Campbell, Liam; Turner, Simon R

    2015-04-20

    The woody tissue of trees is composed of xylem cells that arise from divisions of stem cells within the cambial meristem. The rate of xylem cell formation is dependent upon the rate of cell division within the cambium and is controlled by both genetic and environmental factors. In the annual plant Arabidopsis, signaling between a peptide ligand CLE41 and a receptor kinase PXY controls cambial cell divisions; however, the pathway regulating secondary growth in trees has not been identified. Here, we show that an aspen receptor kinase PttPXY and its peptide ligand PttCLE41 are functional orthologs and act to control a multifunctional pathway that regulates both the rate of cambial cell division and woody tissue organization. Ectopic overexpression of PttPXY and PttCLE41 genes in hybrid aspen resulted in vascular tissue abnormalities and poor plant growth. In contrast, precise tissue-specific overexpression generated trees that exhibited a 2-fold increase in the rate of wood formation, were taller, and possessed larger leaves compared to the controls. Our results demonstrate that the PXY-CLE pathway has evolved to regulate secondary growth and manipulating this pathway can result in dramatically increased tree growth and productivity.

  14. SFRP2 Is Associated with Increased Adiposity and VEGF Expression

    PubMed Central

    Crowley, Rachel K.; Bujalska, Iwona J.; Hassan-Smith, Zaki K.; Hazlehurst, Jonathan M.; Foucault, Danielle R.; Stewart, Paul M.; Tomlinson, Jeremy W.

    2016-01-01

    Aims The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance. Methods Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed. Results sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed. Conclusions Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression. PMID:27685706

  15. Comparative decomposition kinetics of neutral monosaccharides by microwave and induction heating treatments.

    PubMed

    Tsubaki, Shuntaro; Oono, Kiriyo; Onda, Ayumu; Yanagisawa, Kazumichi; Azuma, Jun-ichi

    2013-06-28

    The stabilities of five neutral monosaccharides (glucose, galactose, mannose, arabinose, and xylose) were kinetically compared after the molecules were submitted to microwave heating (internal heating) and induction heating (external heating) under completely identical thermal histories by employing PID (proportional, integral, and derivative) temperature controlled ovens and homogeneous mixing. By heating in water at 200°C, the rate constants for the decomposition reactions varied from 2.13×10(-4) to 3.87×10(-4)s(-1) for microwave heating; however, the values increased by 1.1- to 1.5-fold for induction heating. Similarly, in a dilute (0.8%) sulfuric acid solution, the decomposition rate constants varied from 0.61×10(-3) to 2.00×10(-3)s(-1) for microwave heating; however, the values increased by 1.5- to 2.2-fold for induction heating. The results show that microwave heating imparts greater stability to neutral monosaccharides than does induction heating. The undesirable decomposition of monosaccharides at the surface boundary of reactor walls may have increased the probability of monosaccharide decomposition during induction heating.

  16. Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

    PubMed Central

    Piepenbrink, Michael S.; Samuel, Memorie; Zheng, Bo; Carter, Brittany; Fucile, Christopher; Bunce, Catherine; Kiebala, Michelle; Khan, Atif A.; Thakar, Juilee; Maggirwar, Sanjay B.; Morse, Diane; Rosenberg, Alexander F.; Haughey, Norman J.; Valenti, William; Keefer, Michael C.; Kobie, James J.

    2016-01-01

    Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing

  17. An energy-dense complementary food is associated with a modest increase in weight gain when compared with a fortified porridge in Malawian children aged 6-18 months

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poor complementary feeding practices are associated with stunting and growth faltering throughout the developing world. The objective was to compare the effect of using peanut-/soy-based fortified spread (FS) and corn porridge fortified with fish powder (FP) as complementary foods on growth in rural...

  18. Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species.

    PubMed

    Park, Bo-Yeon; Chung, Jayong

    2009-01-01

    Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism. PMID:20090884

  19. Overexpression of Serpinb1 in Chinese hamster ovary cells increases recombinant IgG productivity.

    PubMed

    Lin, Nan; Brooks, Jeanne; Sealover, Natalie; George, Henry J; Kayser, Kevin J

    2015-01-10

    We report the discovery and validation of a novel CHO cell engineering target for improving IgG expression, serpin peptidase inhibitor, clade B, member 1 (Serpinb1). Transcriptomic studies using microarrays revealed that Serpinb1 was up-regulated in cultures with IgG heavy and light chain transcription transiently repressed compared with cultures treated with non-targeting siRNA. As proof of concept, a lentiviral vector was employed to overexpress the Chinese Hamster Serpinb1 in a CHOZN(®) Glutamine Synthetase (-/-) recombinant IgG producing CHO line. The lentiviral stable pool demonstrated 4.2-fold SERPINB1 overexpression compared with the non-transduced control. The peak viable cell density (VCD) and peak IgG volumetric productivity of the lentiviral stable pool increased 1.3 and 2.0 fold, respectively, compared with the non-transduced control. For host cell engineering, a plasmid encoding SERPINB1 was transfected into the CHOZN(®) GS (-/-) host cell line to create several stable pools. Single-cell clones isolated from the pools were characterized for their SERPINB1 expression levels and growth. The clone (SERPINB1_OE_27) with the highest SERPINB1 expression had decreased peak viable cell density and exponential phase growth rate. Selected SERPINB1 OE clones were subsequently evaluated for their IgG expression capabilities using GS selection. Clone SERPINB1_OE_42 with moderate SERPINB1 overexpression demonstrated increased IgG productivity in "bulk" selection. We conclude that manipulating Serpinb1 expression can lead to increased recombinant IgG productivity, but the effect in host cell lines may vary by clone and by overexpression level. This work represents the ongoing effort in applying "-omics" findings to novel CHO host cell line engineering.

  20. PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion.

    PubMed

    Ho, Maggie M; Johnson, James D; Clee, Susanne M

    2015-04-01

    PWD/PhJ (PWD) is a wild-derived inbred mouse strain unrelated to commonly studied strains, such as C57BL/6J (B6). A chromosome substitution panel with PWD chromosomes transferred into the B6 background is commercially available and will facilitate genetic analysis of this strain. We have previously shown that the PWD strain is a model of primary fasting hyperinsulinemia. To identify more specific phenotypes affected by the genetic variation in PWD compared to B6 mice, we examined physiological mechanisms that may contribute to their elevated insulin levels. PWD mice had increased nutrient-stimulated insulin secretion due to factors inherent to their pancreatic islets. Insulin secretion responses to glucose, palmitate, and the metabolic intermediate α-ketoisocaproate were increased ~2-fold in islets from PWD mice compared to B6 islets. In contrast, there were no strain differences in processes affecting insulin secretion downstream of β cell depolarization. PWD mice tended to have larger but fewer islets than B6 mice, resulting in similar insulin-staining areas and insulin content per unit of pancreatic tissue. However, pancreata of PWD mice were smaller, resulting in reduced total β cell mass and pancreatic insulin content compared to B6 mice. Combined, these data suggest that the elevated fasting insulin levels in PWD mice result from increased generation of metabolic signals leading to β cell depolarization and insulin secretion. Identification of the genetic differences underlying the enhanced nutrient-stimulated insulin secretion in this model may lead to new approaches to appropriately modulate insulin secretion for the treatment of obesity and type 2 diabetes.

  1. Upper-body resistance exercise augments vastus lateralis androgen receptor-DNA binding and canonical Wnt/β-catenin signaling compared to lower-body resistance exercise in resistance-trained men without an acute increase in serum testosterone.

    PubMed

    Spillane, Mike; Schwarz, Neil; Willoughby, Darryn S

    2015-06-01

    The purpose of the study was to determine the effect of single bouts of lower-body (LB) and upper- and lower-body (ULB) resistance exercise on serum testosterone concentrations and the effects on muscle testosterone, dihydrotestosterone (DHT), androgen receptor (AR) protein content, and AR-DNA binding. A secondary purpose was to determine the effects on serum wingless-type MMTV integration site (Wnt4) levels and skeletal muscle β-catenin content. In a randomized cross-over design, exercise bouts consisted of a LB and ULB protocol, and each bout was separated by 1 week. Blood and muscle samples were obtained before exercise and 3 and 24h post-exercise; blood samples were also obtained at 0.5, 1, and 2 h post-exercise. Statistical analyses were performed by separate two-way factorial analyses of variance (ANOVA) with repeated measures. No significant differences from baseline were observed in serum total and free testosterone and skeletal muscle testosterone and DHT with either protocol (p>0.05). AR protein was significantly increased at 3 h post-exercise and decreased at 24 h post-exercise for ULB, whereas AR-DNA binding was significantly increased at 3 and 24h post-exercise (p<0.05). In response to ULB, serum Wnt4 was significantly increased at 0.5, 1, and 2 h post-exercise (p<0.05) and β-catenin was significantly increased at 3 and 24 h post-exercise (p<0.05). It was concluded that, despite a lack of increase in serum testosterone and muscle androgen concentrations from either mode of resistance exercise, ULB resistance exercise increased Wnt4/β-catenin signaling and AR-DNA binding.

  2. Increased uptake of guideline-recommended oral antiplatelet therapy: insights from the Canadian acute coronary syndrome reflective.

    PubMed

    Gandhi, Sumeet; Zile, Brigita; Tan, Mary K; Saranu, Jhansi; Bucci, Claudia; Yan, Andrew T; Robertson, Patrick; Quantz, Mackenzie A; Letovsky, Eric; Tanguay, Jean-Francois; Dery, Jean-Pierre; Fitchett, David; Madan, Mina; Cantor, Warren J; Heffernan, Michael; Natarajan, Madhu K; Wong, Graham C; Welsh, Robert C; Goodman, Shaun G

    2014-12-01

    Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice. PMID:25475475

  3. La Palabra Es Salud: A Comparative Study of the Effectiveness of Popular Education vs. Traditional Education for Enhancing Health Knowledge and Skills and Increasing Empowerment among Parish-Based Community Health Workers

    ERIC Educational Resources Information Center

    Wiggins, Noelle

    2010-01-01

    Popular education is a mode of teaching and learning which seeks to bring about more equitable social conditions by creating settings in which people can identify and solve their own problems. While the public health literature offers evidence to suggest that popular education is an effective strategy for increasing empowerment and improving…

  4. Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery

    PubMed Central

    Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.

    2013-01-01

    The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta®, Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload. PMID:23781287

  5. Association of Beta-Glucan Endogenous Production with Increased Stress Tolerance of Intestinal Lactobacilli▿

    PubMed Central

    Stack, Helena M.; Kearney, Niamh; Stanton, Catherine; Fitzgerald, Gerald F.; Ross, R. Paul

    2010-01-01

    The exopolysaccharide beta-glucan has been reported to be associated with many health-promoting and prebiotic properties. The membrane-associated glycosyltransferase enzyme (encoded by the gtf gene), responsible for microbial beta-glucan production, catalyzes the conversion of sugar nucleotides into beta-glucan. In this study, the gtf gene from Pediococcus parvulus 2.6 was heterologously expressed in Lactobacillus paracasei NFBC 338. When grown in the presence of glucose (7%, wt/vol), the recombinant strain (pNZ44-GTF+) displayed a “ropy” phenotype, while scanning electron microscopy (SEM) revealed strands of polysaccharide-linking neighboring cells. Beta-glucan biosynthesis was confirmed by agglutination tests carried out with Streptococcus pneumoniae type 37-specific antibodies, which specifically detect glucan-producing cells. Further analysis showed a ∼2-fold increase in viscosity in broth media for the beta-glucan-producing strain over 24 h compared to the control strain, which did not show any significant increase in viscosity. In addition, we analyzed the ability of beta-glucan-producing Lactobacillus paracasei NFBC 338 to survive both technological and gastrointestinal stresses. Heat stress assays revealed that production of the polysaccharide was associated with significantly increased protection during heat stress (60-fold), acid stress (20-fold), and simulated gastric juice stress (15-fold). Bile stress assays revealed a more modest but significant 5.5-fold increase in survival for the beta-glucan-producing strain compared to that of the control strain. These results suggest that production of a beta-glucan exopolysaccharide by strains destined for use as probiotics may afford them greater performance/protection during cultivation, processing, and ingestion. As such, expression of the gtf gene may prove to be a straightforward approach to improve strains that might otherwise prove sensitive in such applications. PMID:19933353

  6. Hypothalamic Npy mRNA is correlated with increased wheel running and decreased body fat in calorie-restricted rats.

    PubMed

    Ruegsegger, Gregory N; Speichinger, Katherine R; Manier, Jacob B; Younger, Kyle M; Childs, Thomas E; Booth, Frank W

    2016-04-01

    The neuro-molecular mechanisms that regulate the relationship between physical activity level, energy homeostasis regulation, and body fat are unclear. Thus, we aimed to investigate the relationship between mRNAs in the hypothalamic arcuate nucleus (ARC) related to energy homeostasis, wheel running distance, and body fat in ad lib (AL) and calorie-restricted (CR) growing rats. We hypothesized that changes in select mRNAs (Pomc, Cart, Agrp, Npy, Lepr, Insr, Mc4r, Ampk, Sirt1, Sirt3) in CR would be associated with decreases in body fat percentage and increased wheel running behavior. Male Wistar rats were given access to voluntary running wheels at 4 weeks of age and randomized into AL (n=8) and CR (70% of AL; n=7) groups at 5 weeks of age until study termination at 12 weeks of age. Body composition, serum leptin, insulin, and adiponectin, and ARC mRNA expression in AL and CR rats were assessed and correlated with week-12 running distance to examine potential relationships that may exist. By 12 weeks of age, wheel running was increased ∼3.3-fold (p=0.03) while body fat percentage was ∼2-fold lower in CR compared to AL (p=0.001). Compared to AL, ARC Npy mRNA expression was ∼2-fold greater in CR (p=0.02), while Lepr, Insr, Ampk, and Sirt1 mRNA were additionally increased in CR (p<0.05). Significant correlations existed between ARC Npy mRNA levels versus week-12 wheel running distance (r=0.81, p=0.03), body fat (r=-0.93, p<0.01), and between body fat and wheel running (r=-0.83, p=0.02) in CR, but not in AL. These results reveal possible mechanisms by which fat-brain crosstalk may influence physical activity during energy deficit. These data suggest that below a 'threshold' fat content, body fat may drive activity levels, potentially through hypothalamic Npy action.

  7. Self-organized growth of graphene nanomesh with increased gas sensitivity.

    PubMed

    König, Matthias; Ruhl, Günther; Batke, Joerg-Martin; Lemme, Max C

    2016-08-25

    A bottom-up chemical vapor deposition (CVD) process for the growth of graphene nanomesh films is demonstrated. The process relies on silicon nanospheres to block nucleation sites for graphene CVD on copper substrates. These spheres are formed in a self-organized way through silicon diffusion through a 5 μm copper layer on a silicon wafer coated with 400 nm of silicon nitride. The temperature during the growth process disintegrates the Si3N4 layer and silicon atoms diffuse to the copper surface, where they form the nanospheres. After graphene nanomesh growth, the Si nanospheres can be removed by a simple hydrofluoric acid etch, leaving holes in the graphene film. The nanomesh films have been successfully transferred to different substrates, including gas sensor test structures, and verified and characterized by Auger, TEM and SEM measurements. Electrical/gas-exposure measurements show a 2-fold increase in ammonia sensitivity compared to plain graphene sensors. This improvement can be explained by a higher adsorption site density (edge sites). This new method for nanopatterned graphene is scalable, inexpensive and can be carried out in standard semiconductor industry equipment. Furthermore, the substrates are reusable. PMID:27523310

  8. Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

    PubMed Central

    Majumdar, Gaurav; Majumdar, Abha; Lall, Meena; Verma, Ishwar C.; Upadhyaya, Kailash C.

    2016-01-01

    CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis. PMID:27382234

  9. Comparative Genomics of the Sigatoka Disease Complex on Banana Suggests a Link between Parallel Evolutionary Changes in Pseudocercospora fijiensis and Pseudocercospora eumusae and Increased Virulence on the Banana Host

    PubMed Central

    Chang, Ti-Cheng; Crous, Pedro W.; Stergiopoulos, Ioannis

    2016-01-01

    The Sigatoka disease complex, caused by the closely-related Dothideomycete fungi Pseudocercospora musae (yellow sigatoka), Pseudocercospora eumusae (eumusae leaf spot), and Pseudocercospora fijiensis (black sigatoka), is currently the most devastating disease on banana worldwide. The three species emerged on bananas from a recent common ancestor and show clear differences in virulence, with P. eumusae and P. fijiensis considered the most aggressive. In order to understand the genomic modifications associated with shifts in the species virulence spectra after speciation, and to identify their pathogenic core that can be exploited in disease management programs, we have sequenced and analyzed the genomes of P. eumusae and P. musae and compared them with the available genome sequence of P. fijiensis. Comparative analysis of genome architectures revealed significant differences in genome size, mainly due to different rates of LTR retrotransposon proliferation. Still, gene counts remained relatively equal and in the range of other Dothideomycetes. Phylogenetic reconstruction based on a set of 46 conserved single-copy genes strongly supported an earlier evolutionary radiation of P. fijiensis from P. musae and P. eumusae. However, pairwise analyses of gene content indicated that the more virulent P. eumusae and P. fijiensis share complementary patterns of expansions and contractions in core gene families related to metabolism and enzymatic degradation of plant cell walls, suggesting that the evolution of virulence in these two pathogens has, to some extent, been facilitated by convergent changes in metabolic pathways associated with nutrient acquisition and assimilation. In spite of their common ancestry and shared host-specificity, the three species retain fairly dissimilar repertoires of effector proteins, suggesting that they likely evolved different strategies for manipulating the host immune system. Finally, 234 gene families, including seven putative effectors, were

  10. Comparative Genomics of the Sigatoka Disease Complex on Banana Suggests a Link between Parallel Evolutionary Changes in Pseudocercospora fijiensis and Pseudocercospora eumusae and Increased Virulence on the Banana Host.

    PubMed

    Chang, Ti-Cheng; Salvucci, Anthony; Crous, Pedro W; Stergiopoulos, Ioannis

    2016-08-01

    The Sigatoka disease complex, caused by the closely-related Dothideomycete fungi Pseudocercospora musae (yellow sigatoka), Pseudocercospora eumusae (eumusae leaf spot), and Pseudocercospora fijiensis (black sigatoka), is currently the most devastating disease on banana worldwide. The three species emerged on bananas from a recent common ancestor and show clear differences in virulence, with P. eumusae and P. fijiensis considered the most aggressive. In order to understand the genomic modifications associated with shifts in the species virulence spectra after speciation, and to identify their pathogenic core that can be exploited in disease management programs, we have sequenced and analyzed the genomes of P. eumusae and P. musae and compared them with the available genome sequence of P. fijiensis. Comparative analysis of genome architectures revealed significant differences in genome size, mainly due to different rates of LTR retrotransposon proliferation. Still, gene counts remained relatively equal and in the range of other Dothideomycetes. Phylogenetic reconstruction based on a set of 46 conserved single-copy genes strongly supported an earlier evolutionary radiation of P. fijiensis from P. musae and P. eumusae. However, pairwise analyses of gene content indicated that the more virulent P. eumusae and P. fijiensis share complementary patterns of expansions and contractions in core gene families related to metabolism and enzymatic degradation of plant cell walls, suggesting that the evolution of virulence in these two pathogens has, to some extent, been facilitated by convergent changes in metabolic pathways associated with nutrient acquisition and assimilation. In spite of their common ancestry and shared host-specificity, the three species retain fairly dissimilar repertoires of effector proteins, suggesting that they likely evolved different strategies for manipulating the host immune system. Finally, 234 gene families, including seven putative effectors, were

  11. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    SciTech Connect

    Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  12. Mutations in Succinate Dehydrogenase Subunit C Increase Radiosensitivity and Bystander Responses

    NASA Astrophysics Data System (ADS)

    Zhou, Hongning; Hei, Tom K.

    Although radiation-induced bystander effect is well studied in the past decade, the precise mech-anisms are still unclear. It is likely that a combination of pathways involving both primary and secondary signaling processes is involved in producing a bystander effect. There is recent evidence that mitochondria play a critical role in bystander responses. Recently studies found that a mutation in succinate dehydrogenese subunit C (SDHC), an integral membrane protein in complex II of the electron transport chain, resulted in increased superoxide, oxidative stress, apoptosis, tumorigenesis, and genomic instability, indicating that SDHC play a critical role in maintaining mitochondrial function. In the present study, using Chinese hamster fibroblasts (B1 cells) and the mutants (B9 cells) containing a single base substitution that produced a premature stop codon resulting in a 33-amino acid COOH-terminal truncation of the SDHC protein, we found that B9 cells had an increase in intracellular superoxide content, nitric oxide species, and mitochondrial membrane potential when compared with wild type cells. After irradiated with a grade of doses of gamma rays, B9 cells show an increased radiosensitivity, especially at high doses. The HPRT- mutant yield after gamma-ray irradiation in B9 cells was significantly higher than that of B1 cells. A single, 3Gy dose of gamma-rays increased the background mutant level by more than 4 fold. In contrast, the mutant induction was less than 2 fold in B1 cells. In addition, B9 cells produced a higher bystander mutagenesis after alpha particle irradiation than the B1 cells. Furthermore, pretreated with carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), a nitric oxide scavenger, significantly decreased the bystander effect. Our findings demonstrate that a mutation in SDHC increases radiosensitivity in both directly irradiated cells and in neighboring bystander cells, and mito-chondrial function play an essential role in

  13. The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases.

    PubMed

    Garbers, Christoph; Monhasery, Niloufar; Aparicio-Siegmund, Samadhi; Lokau, Juliane; Baran, Paul; Nowell, Mari A; Jones, Simon A; Rose-John, Stefan; Scheller, Jürgen

    2014-09-01

    The pleiotropic activities of Interleukin (IL-)6 are controlled by membrane-bound and soluble forms of the IL-6 receptor (IL-6R) in processes called classic and trans-signaling, respectively. The coding single nucleotide polymorphism (SNP) rs2228145 of the Interleukin 6 receptor (IL-6R Asp358Ala variant) is associated with a 2-fold increase in soluble IL-6R (sIL-6R) serum levels resulting in reduced IL-6-induced C-reactive protein (CRP) production and a reduced risk for coronary heart disease. It was suggested that the increased sIL-6R level leads to decreased IL-6 classic or increased IL-6 trans-signaling. Irrespective of the functional outcome of increased sIL-6R serum level, it is still under debate, whether the increased sIL-6R serum levels emerged from differential splicing or ectodomain shedding. Here we show that increased proteolytic ectodomain shedding mediated by the A Disintegrin and metalloproteinase domain (ADAM) proteases ADAM10 and ADAM17 caused increased sIL-6R serum level in vitro as well as in healthy volunteers homozygous for the IL-6R Asp358Ala allele. Differential splicing of the IL-6R appears to have only a minor effect on sIL-6R level. Increased ectodomain shedding resulted in reduced cell-surface expression of the IL-6R Asp358Ala variant compared to the common IL-6R variant. In conclusion, increased IL-6R ectodomain shedding is a mechanistic explanation for the increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R Asp358Ala variant.

  14. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    PubMed Central

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  15. Comparing Futures or Comparing Pasts?

    ERIC Educational Resources Information Center

    Cowen, Robert

    2000-01-01

    Comparative education should stop trying to figure out how to borrow educational systems from one culture and transplant them into another. Instead, it should focus on how educational systems can be described and explained, comparatively, in a way that captures the intersections of forces of history, social structures, and individuals' pedagogic…

  16. Increasing Capacity for the Treatment of Common Musculoskeletal Problems: A Non-Inferiority RCT and Economic Analysis of Corticosteroid Injection for Shoulder Pain Comparing a Physiotherapist and Orthopaedic Surgeon

    PubMed Central

    Bisset, Leanne; Comans, Tracy; Thomas, Michael; Ng, Shu Kay; O’Leary, Shaun; Conaghan, Philip G.; Scuffham, Paul A.

    2016-01-01

    at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care. Trial Registration Australia and New Zealand Clinical Trials Registry 12612000532808 PMID:27631987

  17. Human embryonic stem cell-derived mesodermal progenitors display substantially increased tissue formation compared to human mesenchymal stem cells under dynamic culture conditions in a packed bed/column bioreactor.

    PubMed

    de Peppo, Giuseppe Maria; Sladkova, Martina; Sjövall, Peter; Palmquist, Anders; Oudina, Karim; Hyllner, Johan; Thomsen, Peter; Petite, Hervé; Karlsson, Camilla

    2013-01-01

    Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.

  18. A comparative analysis of fatty acid composition of root and shoot lipids in Zea mays under copper and cadmium stress.

    PubMed

    Chaffai, R; Seybou, T N; Marzouk, B; El Ferjani, E

    2009-03-01

    A comparative analysis of fatty acid composition was conducted in maize (Zea mays L.) under copper and cadmium stress. The unsaturation level (double-bond index) of phosphatidylethanolamine (PE) and digalactosyldiacylglycerol (DGDG) was increased in response to both metal treatments, whereas the phosphatidylinositol (PI), the phosphatidylcholine (PC) showed no significant changes. The Cu-treated roots showed a marked increase (about 2-fold) in the phospholipid (PL) content, while the Cd-treated roots showed a slight but insignificant increase. The steryl lipid SL/PL ratio was markedly decreased in response to Cu stress, and therefore, may indicate an activated phospholipid biosynthesis and turnover, in response to damage caused by Cu stress. The double bond indices of chloroplastic lipids: phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG) revealed a similar but not identical pattern of change. The PG and MGDG contents in shoots were markedly decreased under Cu (by 53 and 48%) and Cd (by 78 and 65%) stress. The increase in the malondialdehyde (MDA) content in roots induced by both metals indicates lipid peroxidation. Generally, in the presence of Cu fatty acid composition was markedly modulated but to lesser extent under Cd stress. These results suggest that changes in the fatty acid composition under Cu and Cd stress conditions are metal-specific and may therefore result in differential metal tolerance. PMID:19378928

  19. Increased renal net acid excretion in prematures below 1,600 g body weight compared with prematures and small-for-date newborns above 2,100 g on alimentation with a commercial preterm formula.

    PubMed

    Kalhoff, H; Wiese, B; Kunz, C; Diekmann, L; Stock, G J; Manz, F

    1994-01-01

    In 76 low birth weight infants with an actual body weight ranging from 1,210 to 2,540 g and fed a commercial preterm formula, urine samples were collected and blood acid base status was measured on day 38 (+/- 17, mean +/- SD) of life. Infants with an actual body weight below 1,600 g demonstrated a higher daily weight gain (22 +/- 3 vs. 14 +/- 5 g/kg/day), lower blood pCO2 (35.4 +/- 5.0 vs. 38.9 +/- 3.8 mm Hg), lower urine pH (5.8 +/- 0.5 vs. 6.5 +/- 0.3), higher renal net acid (1.86 +/- 0.38 vs. 1.28 +/- 0.55 mmol/kg/day) and higher phosphorus excretion (0.67 vs. 0.52 mmol/kg/day) than infants with an actual body weight above 2,100 g. Urinary ionogram data of these 2 groups of infants show that the increased renal net acid excretion of the smaller prematures is the result of a lower urinary excretion of sodium, potassium and chloride, due to a higher daily weight gain, probably a higher retention of these minerals, and a higher urinary phosphorus excretion probably due to an age-specific lower intestinal calcium absorption, and therefore a lower rate of calcium and phosphorus retention. Considering the low renal capacity for hydrogen ion excretion, very low birth weight infants still run a considerable risk for disturbances of acid base metabolism due to the high mean level of net acid excretion in nutrition with preterm formulas and an additional age-specific augmentation of renal acid load.

  20. Increased Butyrate Production During Long-Term Fermentation of In Vitro-Digested High Amylose Cornstarch Residues with Human Feces.

    PubMed

    Li, Li; Jiang, Hongxin; Kim, Hyun-Jung; Yum, Man-Yu; Campbell, Mark R; Jane, Jay-Lin; White, Pamela J; Hendrich, Suzanne

    2015-09-01

    An in vitro semi-continuous long-term (3 wk) anaerobic incubation system simulating lower gut fermentation was used to determine variability in gut microbial metabolism between 4 predigested high amylose-resistant starch residues (SR): SRV, SRVI, SRVII, and SRGEMS in human fecal samples. Subjects participated twice, 5 mo apart: 30 in Phase I (15 lean, 9 overweight and 6 obese), 29 in Phase II (15 lean, 9 overweight, 5 obese); 13 of 15 lean subjects participated in both phases. Of the 4 SRs, SRV displayed the highest gelatinization temperature, peak temperature, enthalpy changes, and the least digestibility compared with the other SRs. In both phases, compared with blank controls, all SRs increased butyrate ∼2-fold which stabilized at week 2 and only SRV caused greater propionate concentration (∼30%) after 3 wk which might have been partly mediated by its lesser digestibility. Fecal samples from lean and overweight/obese subjects incubated with SRs showed similar short-chain fatty acid production across both time points, which suggests that resistant starch may benefit individuals across BMIs.

  1. Inhaled Nitric Oxide Increases Urinary Nitric Oxide Metabolites and Cyclic Guanosine Monophosphate in Premature Infants: Relationship to Pulmonary Outcome

    PubMed Central

    Ballard, Philip L.; Keller, Roberta L.; Black, Dennis M.; Durand, David J.; Merrill, Jeffrey D.; Eichenwald, Eric C.; Truog, William E.; Mammel, Mark C.; Steinhorn, Robin; Ryan, Rita M.; Courtney, Sherry E.; Horneman, Hart; Ballard, Roberta A.

    2016-01-01

    Objective Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. Study Design Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20–2 ppm. A control group of 19 infants did not receive iNO. Results In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10–20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. Conclusion Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO–cGMP pathway in lung development. PMID:24968129

  2. Increased nuclear ploidy, not cell proliferation, is sustained in the peroxisome proliferator-treated rat liver.

    PubMed

    Lalwani, N D; Dethloff, L A; Haskins, J R; Robertson, D G; de la Iglesia, F A

    1997-01-01

    Peroxisome proliferators are believed to induce liver tumors in rodents due to sustained increase in cell proliferation and oxidative stress resulting from the induction of peroxisomal enzymes. The objective of this study was to conduct a sequential analysis of the early changes in cell-cycle kinetics and the dynamics of rat liver DNA synthesis after treatment with a peroxisome proliferator. Immunofluorescent detection of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation into DNA during S phase we used to assess rat hepatocyte proliferation in vivo during dietary administration of Wy-14,643, a known peroxisome proliferator and hepatocarcinogen in rodents. Rats were placed on diet containing 0.1% WY-14,643 and implanted subcutaneously with 5-bromo-2'deoxyuridine containing osmotic pumps 4 days prior to being sacrificed on days 4, 11, and 25 of treatment. Isolated liver nuclei labeled with fluorscein isothiocyanate (FITC)-anti-BrdU/PI and FITC-anti-PCNA/PI were analyzed for S-phase kinetics using flow cytometry. Morphometric analysis was performed to evaluate nuclear and cell size and enumeration of BrdU labeled cells, binucleated hepatocytes, and mitotic index. The BrdU labeling index increased 2-fold in livers of Wy-14,643-treated rats at day 4, but distribution of cells in G1, S phase, and G2-M did not differ significantly from controls. PCNA-positive cells decreased from 36% on day 4 to 17% on day 25, whereas the percentage of PCNA-positive cells in controls increased 2-fold from day 4 to day 11 and remained unchanged up to day 25. The differences in the number of PCNA-positive nuclei between control and Wy-14,643-treated groups were statistically significant only on day 4. Binucleated hepatocytes, determined by morphometric analysis, increased slightly on day 25 in treated rats parallel to an increase in the percentage of cells in G2-M phase. Significant shifts were noted in nuclear diameter and nuclear area after 11 and 25

  3. In Inclusion-Body Myositis Muscle Fibers Parkinson-Associated DJ-1 is Increased and Oxidized

    PubMed Central

    Terracciano, Chiara; Nogalska, Anna; Engel, W. King; Wojcik, Slawomir; Askanas, Valerie

    2008-01-01

    Sporadic inclusion-body myositis (s-IBM) is the most common muscle disease of older persons. The muscle-fiber molecular phenotype exhibits similarities to both Alzheimer-disease (AD) and Parkinson-disease (PD) brains, including accumulations of amyloid-β, phosphorylated tau, α-synuclein and parkin, as well as evidence of oxidative stress and mitochondrial abnormalities. Early-onset autosomal-recessive PD can be caused by mutations in the DJ-1 gene, leading to its inactivation. DJ-1 has anti-oxidative and mitochondrial-protective properties. In AD and PD brains, DJ-1 is increased and oxidized. We studied DJ-1 in 17 s-IBM and 18 disease-control and normal muscle biopsies by: 1) immunoblots of muscle homogenates and mitochondrial fractions; 2) real-time PCR; 3) oxyblots evaluating DJ-1 oxidation; 4) light- and electron-microscopic immunocytochemistry. Compared to controls, in s-IBM muscle fibers DJ-1 was: a) increased in the soluble fraction, monomer 2-fold (p=0.01), and dimer 2.8-fold (p=0.004); b) increased in the mitochondrial fraction; c) highly oxidized; and d) aggregated in about 15% of the abnormal muscle fibers. DJ-1 mRNA was increased 3.5-fold (p=0.034). Accordingly, DJ-1 might play a role in human muscle disease, and thus not be limited to human CNS degenerations. In s-IBM muscle fibers, DJ-1 could be protecting these fibers against oxidative stress, including protection of mitochondria. PMID:18601999

  4. A low α-linolenic intake during early life increases adiposity in the adult guinea pig

    PubMed Central

    2010-01-01

    Background The composition of dietary fatty acids (FA) during early life may impact adult adipose tissue (AT) development. We investigated the effects of α-linolenic acid (ALA) intake during the suckling/weaning period on AT development and metabolic markers in the guinea pig (GP). Methods Newborn GP were fed a 27%-fat diet (w/w %) with high (10%-ALA group), moderate (2.4%-ALA group) or low (0.8%-ALA group) ALA content (w/w % as total FA) until they were 21 days old (d21). Then all animals were switched to a 15%-fat diet containing 2% ALA (as total FA) until 136 days of age (d136). Results ALA and docosapentaenoic acid measured in plasma triglycerides (TG) at d21 decreased with decreasing ALA intake. Total body fat mass was not different between groups at d21. Adipose tissue TG synthesis rates and proliferation rate of total adipose cells, as assessed by 2H2O labelling, were unchanged between groups at d21, while hepatic de novo lipogenesis was significantly 2-fold increased in the 0.8%-ALA group. In older GP, the 0.8%-ALA group showed a significant 15-%-increased total fat mass (d79 and d107, p < 0.01) and epididymal AT weight (d136) and tended to show higher insulinemia compared to the 10%-ALA group. In addition, proliferation rate of cells in the subcutaneous AT was higher in the 0.8%-ALA (15.2 ± 1.3% new cells/5d) than in the 10%-ALA group (8.6 ± 1.7% new cells/5d, p = 0.021) at d136. AT eicosanoid profiles were not associated with the increase of AT cell proliferation. Conclusion A low ALA intake during early postnatal life promotes an increased adiposity in the adult GP. PMID:20205840

  5. Quick Compare

    2000-01-10

    Quick Compare is a computer software application that helps a user quickly evaluate alternatives based on criteria and decide on a preferred alternative. The software leads a user through a simple process of defining alternatives and criteria. Then, one person or a group can score the alternatives based on the criteria. The results are immediately displayed in an easy-to-understand graphical output.

  6. Comparative Religions.

    ERIC Educational Resources Information Center

    Cross, M. R.

    The two week course on comparative religions for secondary grade students consists of nine mini-packets. Course objectives for each student are to write a paragraph explaining the fundamental doctrines and concepts of the world religions that he chooses to study and to list the name and address of specific places of worship in the county in which…

  7. Comparative 'Rather.'

    ERIC Educational Resources Information Center

    Dieterich, Thomas G.; Napoli, Donna Jo

    1982-01-01

    Discusses 'rather than' sentences with tensed or untensed verb in second clause as having underlying form of comparative sentences. Concludes 'rather than' preceding a tensed clause represents the truth-functional connective 'and not' which contradicts claim that this connective cannot be represented lexically in natural language and raises…

  8. Heparanase procoagulant activity, factor Xa, and plasminogen activator inhibitor 1 are increased in shift work female nurses.

    PubMed

    Nadir, Yona; Saharov, Gleb; Hoffman, Ron; Keren-Politansky, Anat; Tzoran, Inna; Brenner, Benjamin; Shochat, Tamar

    2015-07-01

    Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underlying mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation system. In the present study, a comparison of coagulation markers among healthy shift working (SW) vs. healthy daytime working (DW) female nurses was performed. Thirty SW and 30 DW female nurses were enrolled. For each of the 60 participants, blood was drawn between 7:00 and 8:00 a.m. and at least 8 h after the last work shift. Plasma was studied for coagulation marker that included TF/heparanase procoagulant activity, TF activity, heparanase procoagulant activity, heparanase level, factor Xa level, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, fibrinogen, global protein C, von Willebrand factor, and D-dimer by chromogenic assays and enzyme-linked immunosorbent assays (ELISAs). Sleep quality was assessed by self-report according to the Pittsburgh Sleep Quality Index. The heparanase procoagulant activity increased by 2-fold and the TF/heparanase procoagulant activity increased by 1.5-fold in SW nurses compared to DW nurses (P < 0.05). Factor Xa levels and PAI-1 levels were significantly higher among SW nurses compared to the DW group (22 vs. 18 ng/ml, P < 0.05, and 32 vs. 22 ng/ml, P < 0.005, respectively). No significant differences were found in the other tested coagulation markers between the study groups. Heparanase procoagulant activity, factor Xa level, and PAI-1 level were significantly higher in SW nurses compared to the DW group. These alterations of blood coagulation activation may potentially contribute to cardiovascular and cancer morbidity.

  9. Comparative activity in vitro of 16 antimicrobial agents against penicillin-susceptible meningococci and meningococci with diminished susceptibility to penicillin.

    PubMed Central

    Pérez Trallero, E; Garcia Arenzana, J M; Ayestaran, I; Muñoz Baroja, I

    1989-01-01

    Broad-spectrum cephalosporins were very active against strains of Neisseria meningitidis with both penicillin susceptibility and diminished penicillin susceptibility. Ceftriaxone was the most active antibiotic. Increases in MIC for 90% of meningococci with diminished susceptibility to penicillin of greater than or equal to 16-fold were observed for amdinocillin, cefuroxime, aztreonam, and imipenem; 2-fold increases were observed for ceftazidime, mezlocillin, and piperacillin. No differences were observed for non-beta-lactam antibiotics. PMID:2510596

  10. Increased Bilateral Interactions in Middle-Aged Subjects

    PubMed Central

    Heetkamp, Jolien; Hortobágyi, Tibor; Zijdewind, Inge

    2014-01-01

    A hallmark of the age-related neural reorganization is that old versus young adults execute typical motor tasks by a more diffuse neural activation pattern including stronger ipsilateral activation during unilateral tasks. Whether such changes in neural activation are present already at middle age and affect bimanual interactions is unknown. We compared the amount of associated activity, i.e., muscle activity and force produced by the non-task hand and motor evoked potentials (MEPs) produced by magnetic brain stimulation between young (mean 24 years, n = 10) and middle-aged (mean 50 years, n = 10) subjects during brief unilateral (seven levels of % maximal voluntary contractions, MVCs) and bilateral contractions (4 × 7 levels of % MVC combinations), and during a 120-s-long MVC of sustained unilateral index finger abduction. During the force production, the excitability of the ipsilateral (iM1) or contralateral primary motor cortex (cM1) was assessed. The associated activity in the “resting” hand was ~2-fold higher in middle-aged (28% of MVC) versus young adults (11% of MVC) during brief unilateral MVCs. After controlling for the background muscle activity, MEPs in iM1 were similar in the two groups during brief unilateral contractions. Only at low (bilateral) forces, MEPs evoked in cM1 were 30% higher in the middle-aged versus young adults. At the start of the sustained contraction, the associated activity was higher in the middle-aged versus young subjects and increased progressively in both groups (30 versus 15% MVC at 120 s, respectively). MEPs were greater at the start of the sustained contraction in middle-aged subjects but increased further during the contraction only in young adults. Under these experimental conditions, the data provide evidence for the reorganization of neural control of unilateral force production as early as age 50. Future studies will determine if the altered neural control of such inter-manual interactions are of

  11. Liver-Specific Expression of Transcriptionally Active SREBP-1c Is Associated with Fatty Liver and Increased Visceral Fat Mass

    PubMed Central

    Knebel, Birgit; Haas, Jutta; Hartwig, Sonja; Jacob, Sylvia; Köllmer, Cornelia; Nitzgen, Ulrike; Muller–Wieland, Dirk; Kotzka, Jorg

    2012-01-01

    The pathogenesis of fatty liver is not understood in detail, but lipid overflow as well as de novo lipogenesis (DNL) seem to be the key points of hepatocyte accumulation of lipids. One key transcription factor in DNL is sterol regulatory element-binding protein (SREBP)-1c. We generated mice with liver-specific over-expression of mature human SREBP-1c under control of the albumin promoter and a liver-specific enhancer (alb-SREBP-1c) to analyze systemic perturbations caused by this distinct alteration. SREBP-1c targets specific genes and causes key enzymes in DNL and lipid metabolism to be up-regulated. The alb-SREBP-1c mice developed hepatic lipid accumulation featuring a fatty liver by the age of 24 weeks under normocaloric nutrition. On a molecular level, clinical parameters and lipid-profiles varied according to the fatty liver phenotype. The desaturation index was increased compared to wild type mice. In liver, fatty acids (FA) were increased by 50% (p<0.01) and lipid composition was shifted to mono unsaturated FA, whereas lipid profile in adipose tissue or serum was not altered. Serum analyses revealed a ∼2-fold (p<0.01) increase in triglycerides and free fatty acids, and a ∼3-fold (p<0.01) increase in insulin levels, indicating insulin resistance; however, no significant cytokine profile alterations have been determined. Interestingly and unexpectedly, mice also developed adipositas with considerably increased visceral adipose tissue, although calorie intake was not different compared to control mice. In conclusion, the alb-SREBP-1c mouse model allowed the elucidation of the systemic impact of SREBP-1c as a central regulator of lipid metabolism in vivo and also demonstrated that the liver is a more active player in metabolic diseases such as visceral obesity and insulin resistance. PMID:22363740

  12. Overexpression of TFAM or Twinkle Increases mtDNA Copy Number and Facilitates Cardioprotection Associated with Limited Mitochondrial Oxidative Stress

    PubMed Central

    Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Arai, Shinobu; Saku, Keita; Kakino, Takamori; Tyynismaa, Henna; Yamasaki, Toshihide; Yamada, Ken-ichi; Kang, Dongchon; Suomalainen, Anu; Sunagawa, Kenji

    2015-01-01

    Background Mitochondrial DNA (mtDNA) copy number decreases in animal and human heart failure (HF), yet its role in cardiomyocytes remains to be elucidated. Thus, we investigated the cardioprotective function of increased mtDNA copy number resulting from the overexpression of human transcription factor A of mitochondria (TFAM) or Twinkle helicase in volume overload (VO)-induced HF. Methods and Results Two strains of transgenic (TG) mice, one overexpressing TFAM and the other overexpressing Twinkle helicase, exhibit an approximately 2-fold equivalent increase in mtDNA copy number in heart. These TG mice display similar attenuations in eccentric hypertrophy and improved cardiac function compared to wild-type (WT) mice without any deterioration of mitochondrial enzymatic activities in response to VO, which was accompanied by a reduction in matrix-metalloproteinase (MMP) activity and reactive oxygen species after 8 weeks of VO. Moreover, acute VO-induced MMP-2 and MMP-9 upregulation was also suppressed at 24 h in both TG mice. In isolated rat cardiomyocytes, mitochondrial reactive oxygen species (mitoROS) upregulated MMP-2 and MMP-9 expression, and human TFAM (hTFAM) overexpression suppressed mitoROS and their upregulation. Additionally, mitoROS were equally suppressed in H9c2 rat cardiomyoblasts that overexpress hTFAM or rat Twinkle, both of which exhibit increased mtDNA copy number. Furthermore, mitoROS and mitochondrial protein oxidation from both TG mice were suppressed compared to WT mice. Conclusions The overexpression of TFAM or Twinkle results in increased mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. Our findings suggest that increasing mtDNA copy number could be a useful therapeutic strategy to target mitoROS in HF. PMID:25822152

  13. Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow.

    PubMed

    Datar, Sanjeev A; Oishi, Peter E; Gong, Wenhui; Bennett, Stephen H; Sun, Christine E; Johengen, Michael; Maki, Jun; Johnson, Rebecca C; Raff, Gary W; Fineman, Jeffrey R

    2014-04-01

    We have previously shown decreased pulmonary lymph flow in our lamb model of chronically increased pulmonary blood flow, created by the in utero placement of an 8-mm aortopulmonary shunt. The purpose of this study was to test the hypothesis that abnormal lymphatic function in shunt lambs is due to impaired lymphatic endothelial nitric oxide (NO)-cGMP signaling resulting in increased lymphatic vascular constriction and/or impaired relaxation. Thoracic duct rings were isolated from 4-wk-old shunt (n = 7) and normal (n = 7) lambs to determine length-tension properties, vascular reactivity, and endothelial NO synthase protein. At baseline, shunt thoracic duct rings had 2.6-fold higher peak to peak tension and a 2-fold increase in the strength of contractions compared with normal rings (P < 0.05). In response to norepinephrine, shunt thoracic duct rings had a 2.4-fold increase in vascular tone compared with normal rings (P < 0.05) and impaired relaxation in response to the endothelium-dependent dilator acetylcholine (63% vs. 13%, P < 0.05). In vivo, inhaled NO (40 ppm) increased pulmonary lymph flow (normalized for resistance) ∼1.5-fold in both normal and shunt lambs (P < 0.05). Inhaled NO exposure increased bioavailable NO [nitrite/nitrate (NOx); ∼2.5-fold in normal lambs and ∼3.4-fold in shunt lambs] and cGMP (∼2.5-fold in both) in the pulmonary lymph effluent (P < 0.05). Chronic exposure to increased pulmonary blood flow is associated with pulmonary lymphatic endothelial injury that disrupts NO-cGMP signaling, leading to increased resting vasoconstriction, increased maximal strength of contraction, and impaired endothelium-dependent relaxation. Inhaled NO increases pulmonary lymph NOx and cGMP levels and pulmonary lymph flow in normal and shunt lambs. Therapies that augment NO-cGMP signaling within the lymphatic system may provide benefits, warranting further study.

  14. Increased CSF Homocysteine in Pathological Gamblers Compared with Healthy Controls

    ERIC Educational Resources Information Center

    Nordin, Conny; Sjodin, Ingemar

    2009-01-01

    Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11…

  15. Insulin increases phosphorylation of mitochondrial proteins in human skeletal muscle in vivo.

    PubMed

    Zhao, Xiaolu; Bak, Steffen; Pedersen, Andreas J T; Jensen, Ole Nørregaard; Højlund, Kurt

    2014-05-01

    There is increasing evidence that multiple proteins involved in key regulatory processes in mitochondria are phosphorylated in mammalian tissues. Insulin regulates glucose metabolism by phosphorylation-dependent signaling and has been shown to stimulate ATP synthesis in human skeletal muscle. Here, we investigated the effect of insulin on the phosphorylation of mitochondrial proteins in human skeletal muscle in vivo. Using a combination of TiO(2) phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS, we compared the phosphoproteomes of isolated mitochondria from skeletal muscle samples obtained from healthy individuals before and after 4 h of insulin infusion. In total, we identified 207 phosphorylation sites in 95 mitochondrial proteins. Of these phosphorylation sites, 45% were identified in both basal and insulin-stimulated samples. Insulin caused a 2-fold increase in the number of different mitochondrial phosphopeptides (87 ± 7 vs 40 ± 7, p = 0.015) and phosphoproteins (46 ± 2 vs 26 ± 3, p = 0.005) identified in each mitochondrial preparation. Almost half of the mitochondrial phosphorylation sites (n = 94) were exclusively identified in the insulin-stimulated state and included the majority of novel sites. Phosphorylation sites detected more often or exclusively in insulin-stimulated samples include multiple sites in mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle, and fatty acid metabolism, as well as several components of the newly defined mitochondrial inner membrane organizing system (MINOS). In conclusion, the present study demonstrates that insulin increases the phosphorylation of several mitochondrial proteins in human skeletal muscle in vivo and provides a first step in the understanding of how insulin potentially regulates mitochondrial processes by phosphorylation-dependent mechanisms.

  16. Dexamethasone Increases αvβ3 Integrin Expression and Affinity through a Calcineurin/NFAT Pathway

    PubMed Central

    Faralli, Jennifer A.; Gagen, Debjani; Filla, Mark S.; Crotti, Tania N.; Peters, Donna M.

    2013-01-01

    The purpose of this study was to determine how dexamethasone (DEX) regulates the expression and activity of αvβ3 integrin. FACS analysis showed that DEX treatment induced expression of an activated αvβ3 integrin. Its expression remained high as long as DEX was present and continued following DEX removal. FACS analysis showed that the upregulation of αvβ3 integrin was the result of an increase in the expression of the β3 integrin subunit. By real time qPCR, DEX treatment induced a 6.2-fold increase (p<0.04) in β3 integrin mRNA by day 2 compared to control and remained elevated for 6 days of treatment and then an additional 10 days once the DEX was removed. The increase in β3 integrin mRNA levels required only 1 day of DEX treatment to increase levels for 4 days in the absence of DEX. In contrast, DEX did not alter β1 integrin mRNA or protein levels. The DEX-induced upregulation of β3 integrin mRNA was partly due to an increase in its half-life to 60.7 h from 22.5 h in control cultures (p<0.05) and could be inhibited by RU486 and cycloheximide, suggesting that DEX-induced de novo protein synthesis of an activation factor was needed. The calcineurin inhibitors cyclosporin A (CsA) and FK506 inhibited the DEX induced increase in β3 integrin mRNA. In summary, the DEX-induced increase in β3 integrin is a secondary glucocorticoid response that results in prolonged expression of αvβ3 integrin and the upregulation of the β3 integrin subunit through the calcineurin/NFAT pathway. PMID:24100160

  17. Contemporary reliance on bicarbonate acquisition predicts increased growth of seagrass Amphibolis antarctica in a high-CO2 world

    PubMed Central

    Burnell, Owen W.; Connell, Sean D.; Irving, Andrew D.; Watling, Jennifer R.; Russell, Bayden D.

    2014-01-01

    Rising atmospheric CO2 is increasing the availability of dissolved CO2 in the ocean relative to HCO3−. Currently, many marine primary producers use HCO3− for photosynthesis, but this is energetically costly. Increasing passive CO2 uptake relative to HCO3− pathways could provide energy savings, leading to increased productivity and growth of marine plants. Inorganic carbon-uptake mechanisms in the seagrass Amphibolis antarctica were determined using the carbonic anhydrase inhibitor acetazolamide (AZ) and the buffer tris(hydroxymethyl)aminomethane (TRIS). Amphibolis antarctica seedlings were also maintained in current and forecasted CO2 concentrations to measure their physiology and growth. Photosynthesis of A. antarctica was significantly reduced by AZ and TRIS, indicating utilization of HCO3−-uptake mechanisms. When acclimated plants were switched between CO2 treatments, the photosynthetic rate was dependent on measurement conditions but not growth conditions, indicating a dynamic response to changes in dissolved CO2 concentration, rather than lasting effects of acclimation. At forecast CO2 concentrations, seedlings had a greater maximum electron transport rate (1.4-fold), photosynthesis (2.1-fold), below-ground biomass (1.7-fold) and increase in leaf number (2-fold) relative to plants in the current CO2 concentration. The greater increase in photosynthesis (measured as O2 production) compared with the electron transport rate at forecasted CO2 concentration suggests that photosynthetic efficiency increased, possibly due to a decrease in photorespiration. Thus, it appears that the photosynthesis and growth of seagrasses reliant on energetically costly HCO3− acquisition, such as A. antarctica, might increase at forecasted CO2 concentrations. Greater growth might enhance the future prosperity and rehabilitation of these important habitat-forming plants, which have experienced declines of global significance. PMID:27293673

  18. Contemporary reliance on bicarbonate acquisition predicts increased growth of seagrass Amphibolis antarctica in a high-CO2 world.

    PubMed

    Burnell, Owen W; Connell, Sean D; Irving, Andrew D; Watling, Jennifer R; Russell, Bayden D

    2014-01-01

    Rising atmospheric CO2 is increasing the availability of dissolved CO2 in the ocean relative to HCO3 (-). Currently, many marine primary producers use HCO3 (-) for photosynthesis, but this is energetically costly. Increasing passive CO2 uptake relative to HCO3 (-) pathways could provide energy savings, leading to increased productivity and growth of marine plants. Inorganic carbon-uptake mechanisms in the seagrass Amphibolis antarctica were determined using the carbonic anhydrase inhibitor acetazolamide (AZ) and the buffer tris(hydroxymethyl)aminomethane (TRIS). Amphibolis antarctica seedlings were also maintained in current and forecasted CO2 concentrations to measure their physiology and growth. Photosynthesis of A. antarctica was significantly reduced by AZ and TRIS, indicating utilization of HCO3 (-)-uptake mechanisms. When acclimated plants were switched between CO2 treatments, the photosynthetic rate was dependent on measurement conditions but not growth conditions, indicating a dynamic response to changes in dissolved CO2 concentration, rather than lasting effects of acclimation. At forecast CO2 concentrations, seedlings had a greater maximum electron transport rate (1.4-fold), photosynthesis (2.1-fold), below-ground biomass (1.7-fold) and increase in leaf number (2-fold) relative to plants in the current CO2 concentration. The greater increase in photosynthesis (measured as O2 production) compared with the electron transport rate at forecasted CO2 concentration suggests that photosynthetic efficiency increased, possibly due to a decrease in photorespiration. Thus, it appears that the photosynthesis and growth of seagrasses reliant on energetically costly HCO3 (-) acquisition, such as A. antarctica, might increase at forecasted CO2 concentrations. Greater growth might enhance the future prosperity and rehabilitation of these important habitat-forming plants, which have experienced declines of global significance.

  19. Compartmentalized self-replication under fast PCR cycling conditions yields Taq DNA polymerase mutants with increased DNA-binding affinity and blood resistance

    PubMed Central

    Arezi, Bahram; McKinney, Nancy; Hansen, Connie; Cayouette, Michelle; Fox, Jeffrey; Chen, Keith; Lapira, Jennifer; Hamilton, Sarah; Hogrefe, Holly

    2014-01-01

    Faster-cycling PCR formulations, protocols, and instruments have been developed to address the need for increased throughput and shorter turn-around times for PCR-based assays. Although run times can be cut by up to 50%, shorter cycle times have been correlated with lower detection sensitivity and increased variability. To address these concerns, we applied Compartmentalized Self Replication (CSR) to evolve faster-cycling mutants of Taq DNA polymerase. After five rounds of selection using progressively shorter PCR extension times, individual mutations identified in the fastest-cycling clones were randomly combined using ligation-based multi-site mutagenesis. The best-performing combinatorial mutants exhibit 35- to 90-fold higher affinity (lower Kd) for primed template and a moderate (2-fold) increase in extension rate compared to wild-type Taq. Further characterization revealed that CSR-selected mutations provide increased resistance to inhibitors, and most notably, enable direct amplification from up to 65% whole blood. We discuss the contribution of individual mutations to fast-cycling and blood-resistant phenotypes. PMID:25177317

  20. Comparative toxicities of bismuth oxybromide and titanium dioxide exposure on human skin keratinocyte cells.

    PubMed

    Gao, Xiaoya; Wang, Yawen; Peng, Shiqi; Yue, Bin; Fan, Caimei; Chen, Weiyi; Li, Xiaona

    2015-09-01

    Nano-sized bismuth oxybromide (BiOBr) particles are being considered for applications within the semiconductor industry. However, little is known about their potential impact on human health. In this study, we comparatively investigated the cytotoxicity of BiOBr and titanium dioxide (TiO2) nanoparticles (NPs) using human skin keratinocyte cell line (HaCaT) as a research model. Results indicate that lamellar-shaped BiOBr (length: 200 nm, width: 150 nm, and an average thickness: around 15 nm) has less toxic effects on cell viability and intracellular organelles than TiO2 (P25) NPs. BiOBr mainly induced late cell apoptosis, while for TiO2, both early apoptosis and late apoptosis were involved. Cell cycle arrest was found in cells on both NPs exposure, and more prominent in TiO2-treated cells. More cellular uptake was achieved after TiO2 exposure, particularly at 10 μg mL(-1), presence of TiO2 resulted in more than 2-fold increase in cellular granularity compared with BiOBr. Furthermore, TiO2 had a high potential to generate intracellular reactive oxygen species (ROS) in cells, where a 2.7-fold increase in TiO2 group and 2.0-fold increase in BiOBr group at the same concentration of 25 μg mL(-1). Higher cellular uptake and ROS stimulation should contribute to the more hazards of TiO2 than BiOBr NPs. This knowledge is a crucial component in the environmental and human hazard assessment of BiOBr and TiO2 NPs.

  1. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  2. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging.

    PubMed

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C; Larin, Kirill V

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  3. Comparative metacognition.

    PubMed

    Terrace, Herbert S; Son, Lisa K

    2009-02-01

    Metacognition is knowledge about knowledge, often expressed as confidence judgments about what we know. Most of the literature on metacognition in humans is based on subjects' verbal reports. Investigators of animal cognition have recently described nonverbal methods for investigating metacognition in animals. In one, subjects are given the option to escape from difficult trials. In another, subjects are trained to place bets about the accuracy of their most recent response. To rule out noncognitive interpretations of purported evidence of metacognition in animals, one must ensure that escape responses do not increase the overall density of reinforcement and that they do not occur in the presence of the stimuli on which the subject was trained. The nonverbal techniques used to investigate metacognition in animals make possible two interesting lines of research: investigating the contribution of language and explicit instruction in establishing metacognition, and the investigation of the neural substrates of metacognition. PMID:19553102

  4. [Increased risk of stillbirth in older mothers--a rationale for induction of labour before term?].

    PubMed

    Rath, W; Wolff, F

    2014-10-01

    The average age of childbearing has risen markedly in Germany and other high-income countries during the past 2 decades. Women aged 35 years or older have an increase in pregnancy complications and in preexisting medical conditions including obesity, diabetes and hypertension as well as a significant increase in the gestational age-related rate of stillbirth compared to younger mothers. Additional individual risk factors for stillbirth are primiparity, body mass index>30 and smoking. After exclusion of risk factors the absolute risk of stillbirth in women aged≥40 years old is 2-fold higher (1 in 503 maternities) at 39/40 weeks of gestation compared to women aged<35 years (1 in 1 020 maternities) at the same gestational age. Women aged 40 years or older have a similar stillbirth risk at 39 weeks of gestation to 25-29-year-olds at 41 weeks gestation. The underlying mechanism for the excess risk of stillbirth in women of advanced maternal age after exclusion of congenital anomalies is unknown. Independent of maternal age the cumulative probability of perinatal death increases from 1.8/1 000 deliveries at 38 weeks of gestation to 9.3/1 000 deliveries at 42 weeks of gestation. Whether on the basis of these data induction of labour at 39 weeks of gestation should be recommended in women of advanced maternal age has recently been discussed in a Scientific Impact Paper of the Royal College of Obstetricians and Gynaecologists. In this context it should be taken into account that the rate of Caesarean sections in women aged 40 years or over is 40%, and, in particular, older nulliparous may request elective Caesaran section rather than elective induction of labour. Recent metaanalyses have shown that elective induction of labour before or after term is not associated with an increase of the Caesarean section rate compared to expectant management. Up to now no randomised controlled trials exist and consequently no -recommendations from current guidelines regarding

  5. Increased microsomal interaction with iron and oxygen radical generation after chronic acetone treatment.

    PubMed

    Puntarulo, S; Cederbaum, A I

    1988-01-12

    In vivo administration of acetone influences a variety of reactions catalyzed by rat liver microsomes. The effect of chronic treatment with acetone (1% acetone in the water for 10-12 days) on interaction with iron and subsequent oxygen radical generation by liver microsomes was evaluated. Microsomes from the acetone-treated rats displayed elevated rates of H2O2 generation, an increase in iron-dependent lipid peroxidation, and enhanced chemiluminescence upon the addition of t-butylhydroperoxide. The ferric EDTA-catalyzed production of formaldehyde from DMSO or of ethylene from 2-keto-4-thiomethylbutyrate was increased 2-fold after acetone treatment. This increase in hydroxyl radical generation was accompanied by a corresponding increase in NADPH utilization and was sensitive to inhibition by catalase and a competitive scavenger, ethanol, but not to superoxide dismutase. In vitro addition of acetone to microsomes had no effect on oxygen radical generation. Associated with the chronic acetone treatment was a 2-fold increase in the microsomal content of cytochrome P-450 and in the activity of NADPH-cytochrome-P-450 reductase. It appears that increased oxygen radical generation by microsomes after chronic acetone treatment reflects the increase in the major enzyme components which comprise the mixed-function oxidase system.

  6. THE CANNABINOID RECEPTOR ANTAGONIST AM251 INCREASES PARAOXON AND CHLORPYRIFOS OXON TOXICITY IN RATS

    PubMed Central

    Liu, Jing; Pope, Carey

    2014-01-01

    Organophosphorus anticholinesterases (OPs) elicit acute toxicity by inhibiting acetylcholinesterase (AChE), leading to acetylcholine accumulation and overstimulation of cholinergic receptors. Endocannabinoids (eCBs, e.g., arachidonoyl ethanolamide [AEA] and 2-arachidonoyl glycerol [2-AG]) are neuromodulators that regulate neurotransmission by reducing neurotransmitter release. The eCBs are degraded by the enzymes fatty acid amide hydrolase (FAAH, primarily involved in hydrolysis of AEA) and monoacylglycerol lipase (MAGL, primarily responsible for metabolism of 2-AG). We previously reported that the cannabinoid receptor agonist WIN 55,212-2 reduced cholinergic toxicity after paraoxon exposure. This study compared the effects of the cannabinoid receptor antagonist AM251 on acute toxicity following either paraoxon (PO) or chlorpyrifos oxon (CPO). CPO was more potent in vitro than PO at inhibiting AChE (≈ 2 fold), FAAH (≈ 8 fold), and MAGL (≈ 19 fold). Rats were treated with vehicle, PO (0.3 and 0.6 mg/kg, sc.) or CPO (6 and 12 mg/kg, sc.) and subsets treated with AM251 (3 mg/kg, ip; 30 min after OP). Signs of toxicity were recorded for four hours and rats were then sacrificed. OP-treated rats showed dose-related involuntary movements, with AM251 increasing signs of toxicity with the lower dosages. PO and CPO elicited excessive secretions, but AM251 had no apparent effect with either OP. Lethality was increased by AM251 with the higher dosage of PO, but no lethality was noted with either dosage of CPO, with or without AM251. Both OPs caused extensive inhibition of hippocampal AChE and FAAH (>80–90%), but only CPO inhibited MAGL (37–50%). These results provide further evidence that eCB signaling can influence acute OP toxicity. The selective in vivo inhibition of MAGL by CPO may be important in the differential lethality noted between PO and CPO with AM251 co-administration. PMID:25447325

  7. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  8. Increased Epithelial Sodium Channel Activity Contributes to Hypertension Caused by Na+-HCO3- Cotransporter Electrogenic 2 Deficiency.

    PubMed

    Wen, Donghai; Yuan, Yang; Warner, Paige C; Wang, Bangchen; Cornelius, Ryan J; Wang-France, Jun; Li, Huaqing; Boettger, Thomas; Sansom, Steven C

    2015-07-01

    The gene SLC4A5 encodes the Na(+)-HCO3 (-) cotransporter electrogenic 2, which is located in the distal nephron. Genetically deleting Na(+)-HCO3 (-) cotransporter electrogenic 2 (knockout) causes Na(+)-retention and hypertension, a phenotype that is diminished with alkali loading. We performed experiments with acid-loaded mice and determined whether overactive epithelial Na(+) channels (ENaC) or the Na(+)-Cl(-) cotransporter causes the Na(+) retention and hypertension in knockout. In untreated mice, the mean arterial pressure was higher in knockout, compared with wild-type (WT); however, treatment with amiloride, a blocker of ENaC, abolished this difference. In contrast, hydrochlorothiazide, an inhibitor of Na(+)-Cl(-) cotransporter, decreased mean arterial pressure in WT, but not knockout. Western blots showed that quantity of plasmalemmal full-length ENaC-α was significantly higher in knockout than in WT. Amiloride treatment caused a 2-fold greater increase in Na(+) excretion in knockout, compared with WT. In knockout, but not WT, amiloride treatment decreased plasma [Na(+)] and urinary K(+) excretion, but increased hematocrit and plasma [K(+)] significantly. Micropuncture with microelectrodes showed that the [K(+)] was significantly higher and the transepithelial potential (Vte) was significantly lower in the late distal tubule of the knockout compared with WT. The reduced Vte in knockout was amiloride sensitive and therefore revealed an upregulation of electrogenic ENaC-mediated Na(+) reabsorption in this segment. These results show that, in the absence of Na(+)-HCO3 (-) cotransporter electrogenic 2 in the late distal tubule, acid-loaded mice exhibit disinhibition of ENaC-mediated Na(+) reabsorption, which results in Na(+) retention, K(+) wasting, and hypertension.

  9. Comparative characterization of microRNAs in Schistosoma japonicum schistosomula from Wistar rats and BALB/c mice.

    PubMed

    Han, Hongxiao; Peng, Jinbiao; Hong, Yang; Fu, Zhiqiang; Lu, Ke; Li, Hao; Zhu, Chuangang; Zhao, Qiuhua; Lin, Jiaojiao

    2015-07-01

    More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum) (Peng et al. Parasitol Res 106:967-76, 2010). Compared with permissive BALB/c mice, rats are less susceptible to S. japonicum infection and are considered to provide an unsuitable microenvironment for parasite growth and development. MicroRNAs (miRNAs), via the regulation of gene expression at the transcriptional and post-transcriptional levels, may be responsible for developmental differences between schistosomula in these two rodent hosts. Solexa deep-sequencing technology was used to identify differentially expressed miRNAs from schistosomula isolated from Wistar rats and BALB/c mice 10 days post-infection. The deep-sequencing analysis revealed that nearly 40 % of raw reads (10.37 and 10.84 million reads in schistosomula isolated from Wistar rats and BALB/c mice, respectively) can be mapped to selected mirs in miRBase or in species-specific genomes. Further analysis revealed that several miRNAs were differentially expressed in schistosomula isolated from these two rodents; 18 were downregulated (by <2-fold) and 23 were up-regulated (>2-fold) (expression levels in rats compare with those in mice). Additionally, three novel miRNAs were primarily predicted and identified. Among the 41 differentially expressed miRNAs, 4 miRNAs had been identified with specific functions in schistosome development or host-parasite interaction, such as sexual maturation (sja-miR-1, sja-miR-7-5p), embryo development (sja-miR-36-3p) in schistosome, and pathogenesis of schistosomiasis (sja-bantam). Then, the target genes were mapped, filtered, and correlated with a set of genes that were differentially expressed genes in schistosomula isolated from mice and rats, which we identified in a S. japonicum oligonucleotide microarray analysis in a previous study. Gene Ontology (GO) analysis of the predicted target genes of 13 differentially expressed miRNAs revealed that they

  10. Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis[S

    PubMed Central

    Vaisman, Boris L.; Demosky, Stephen J.; Stonik, John A.; Ghias, Mona; Knapper, Cathy L.; Sampson, Maureen L.; Dai, Cuilian; Levine, Stewart J.; Remaley, Alan T.

    2012-01-01

    The role of endothelial ABCA1 expression in reverse cholesterol transport (RCT) was examined in transgenic mice, using the endothelial-specific Tie2 promoter. Human ABCA1 (hABCA1) was significantly expressed in endothelial cells (EC) of most tissues except the liver. Increased expression of ABCA1 was not observed in resident peritoneal macrophages. ApoA-I-mediated cholesterol efflux from aortic EC was 2.6-fold higher (P < 0.0001) for cells from transgenic versus control mice. On normal chow diet, Tie2 hABCA1 transgenic mice had a 25% (P < 0.0001) increase in HDL-cholesterol (HDL-C) and more than a 2-fold increase of eNOS mRNA in the aorta (P < 0.04). After 6 months on a high-fat, high-cholesterol (HFHC) diet, transgenic mice compared with controls had a 40% increase in plasma HDL-C (P < 0.003) and close to 40% decrease in aortic lesions (P < 0.02). Aortas from HFHC-fed transgenic mice also showed gene expression changes consistent with decreased inflammation and apoptosis. Beneficial effects of the ABCA1 transgene on HDL-C levels or on atherosclerosis were absent when the transgene was transferred onto ApoE or Abca1 knockout mice. In summary, expression of hABCA1 in EC appears to play a role in decreasing diet-induced atherosclerosis in mice and is associated with increased plasma HDL-C levels and beneficial gene expression changes in EC. PMID:22039582

  11. Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1alpha and HIF-2alpha.

    PubMed

    Yoon, Donghoon; Okhotin, David V; Kim, Bumjun; Okhotina, Yulia; Okhotin, Daniel J; Miasnikova, Galina Y; Sergueeva, Adelina I; Polyakova, Lydia A; Maslow, Alexei; Lee, Yonggu; Semenza, Gregg L; Prchal, Josef T; Gordeuk, Victor R

    2010-05-01

    Chuvash polycythemia, the first hereditary disease associated with dysregulated oxygen-sensing to be recognized, is characterized by a homozygous germ-line loss-of-function mutation of the VHL gene (VHL(R200W)) resulting in elevated hypoxia inducible factor (HIF)-1alpha and HIF-2alpha levels, increased red cell mass and propensity to thrombosis. Organ volume is determined by the size and number of cells, and the underlying molecular control mechanisms are not fully elucidated. Work from several groups has demonstrated that the proliferation of cells is regulated in opposite directions by HIF-1alpha and HIF-2alpha. HIF-1alpha inhibits cell proliferation by displacing MYC from the promoter of the gene encoding the cyclin-dependent kinase inhibitor, p21(Cip1), thereby inducing its expression. In contrast, HIF-2alpha promotes MYC activity and cell proliferation. Here we report that the volumes of liver, spleen, and kidneys relative to body mass were larger in 30 individuals with Chuvash polycythemia than in 30 matched Chuvash controls. In Hif1a(+/-) mice, which are heterozygous for a null (knockout) allele at the locus encoding HIF-1alpha, hepatic HIF-2alpha mRNA was increased (2-fold) and the mass of the liver was increased, compared with wild-type littermates, without significant difference in cell volume. Hepatic p21(Cip1) mRNA levels were 9.5-fold lower in Hif1a(+/-) mice compared with wild-type littermates. These data suggest that, in addition to increased red cell mass, the sizes of liver, spleen, and kidneys are increased in Chuvash polycythemia. At least in the liver, this phenotype may result from increased HIF-2alpha and decreased p21(Cip1) levels leading to increased hepatocyte proliferation. PMID:20140661

  12. Comparative Evaluation of Biochemical Changes in Tomato (Lycopersicon esculentum Mill.) Infected by Alternaria alternata and Its Toxic Metabolites (TeA, AOH, and AME)

    PubMed Central

    Meena, Mukesh; Zehra, Andleeb; Dubey, Manish K.; Aamir, Mohd; Gupta, Vijai K.; Upadhyay, Ram S.

    2016-01-01

    In the present study, we have evaluated the comparative biochemical defense response generated against Alternaria alternata and its purified toxins viz. alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA). The necrotic lesions developed due to treatment with toxins were almost similar as those produced by the pathogen, indicating the crucial role of these toxins in plant pathogenesis. An oxidative burst reaction characterized by the rapid and transient production of a large amount of reactive oxygen species (ROS) occurs following the pathogen infection/toxin exposure. The maximum concentration of hydrogen peroxide (H2O2) produced was reported in the pathogen infected samples (22.2-fold) at 24 h post inoculation followed by TeA (18.2-fold), AOH (15.9-fold), and AME (14.1-fold) in treated tissues. 3,3′- Diaminobenzidine staining predicted the possible sites of H2O2 accumulation while the extent of cell death was measured by Evans blue dye. The extent of lipid peroxidation and malondialdehyde (MDA) content was higher (15.8-fold) at 48 h in the sample of inoculated leaves of the pathogen when compared to control. The cellular damages were observed as increased MDA content and reduced chlorophyll. The activities of antioxidative defense enzymes increased in both the pathogen infected as well as toxin treated samples. Superoxide dismutase (SOD) activity was 5.9-fold higher at 24 h post inoculation in leaves followed by TeA (5.0-fold), AOH (4.1-fold) and AME (2.3-fold) treated leaves than control. Catalase (CAT) activity was found to be increased upto 48 h post inoculation and maximum in the pathogen challenged samples followed by other toxins. The native PAGE results showed the variations in the intensities of isozyme (SOD and CAT) bands in the pathogen infected and toxin treated samples. Ascorbate peroxidase (APx) and glutathione reductase (GR) activities followed the similar trend to scavenge the excess H2O2. The reduction in CAT

  13. Comparative genomics - a perspective.

    PubMed

    Sivashankari, Selvarajan; Shanmughavel, Piramanayagam

    2007-03-27

    The rapidly emerging field of comparative genomics has yielded dramatic results. Comparative genome analysis has become feasible with the availability of a number of completely sequenced genomes. Comparison of complete genomes between organisms allow for global views on genome evolution and the availability of many completely sequenced genomes increases the predictive power in deciphering the hidden information in genome design, function and evolution. Thus, comparison of human genes with genes from other genomes in a genomic landscape could help assign novel functions for un-annotated genes. Here, we discuss the recently used techniques for comparative genomics and their derived inferences in genome biology.

  14. Comparative genomics - A perspective

    PubMed Central

    Sivashankari, Selvarajan; Shanmughavel, Piramanayagam

    2007-01-01

    The rapidly emerging field of comparative genomics has yielded dramatic results. Comparative genome analysis has become feasible with the availability of a number of completely sequenced genomes. Comparison of complete genomes between organisms allow for global views on genome evolution and the availability of many completely sequenced genomes increases the predictive power in deciphering the hidden information in genome design, function and evolution. Thus, comparison of human genes with genes from other genomes in a genomic landscape could help assign novel functions for un-annotated genes. Here, we discuss the recently used techniques for comparative genomics and their derived inferences in genome biology. PMID:17597925

  15. Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

    PubMed

    Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

    2016-07-01

    Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID:27251042

  16. Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

    PubMed

    Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

    2016-07-01

    Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI.

  17. Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression.

    PubMed

    Hainault, I; Guerre-Millo, M; Guichard, C; Lavau, M

    1991-03-01

    Adipocytes from young obese Zucker rats exhibit a hyperresponsive insulin-mediated glucose transport, together with a marked increase in cytochalasin B binding as compared with lean rat adipocytes. Here, we examined in these cells the expression of two isoforms of glucose transporter, the erythroid (GLUT 1) and the adipose cell/muscle (GLUT 4) types, in rats aged 16 or 30 d, i.e., before and after the emergence of hyperinsulinemia. GLUT 1 protein and mRNA levels were identical in the two genotypes at both ages. In contrast, the levels of GLUT 4 protein in obese rat adipocytes were 2.4- and 4.5-fold those of lean littermates at 16 and 30 d of age, respectively, in perfect agreement with the genotype effect on insulin-stimulated glucose transport activity. The levels of GLUT 4 mRNA per fat pad were increased 2.3- and 6.2-fold in obese vs. lean rats 16- and 30-d-old, indicating a pretranslational level of regulation. The obese phenotype was not associated with overexpression of GLUT 4 mRNA in gastrocnemius muscle. This work indicates that the fa gene exerts a differential control on the expression of GLUT 1 and GLUT 4 in adipose tissue and provides evidence that independent of hyperinsulinemia, genotype is a major regulatory factor of GLUT 4 expression in this tissue.

  18. Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats

    PubMed Central

    Feng, Xin-Chan; Du, Xiaohuang; Chen, Sheng; Yue, Dongmei; Cheng, Ying; Zhang, Liangjun; Gao, Yu; Li, Shaoxue; Chen, Lei; Peng, Zhihong; Yang, Yong; Luo, Weizao; Wang, Rongquan; Chen, Wensheng; Chai, Jin

    2015-01-01

    Swertianlarin, isolated from Swertia mussotii Franch and Enicostemma axillare, has hepatoprotective effects against cholestasis in rat models of hepatotoxicity. However, the underlying molecular mechanism is not clear. We then treated rats with swertianlarin for 7 d and then measured serum liver injury markers, lipids, and bile salts, as well as the expression of bile acid synthesis and detoxification enzymes (e.g. Cyp7a1 and Cyp3a), membrane influx and efflux transporters (e.g. Ntcp and Mrp3), nuclear receptors (e.g. Pxr and Fxr/Shp) and transcriptional factors (e.g. Nrf2 and Hnf3β) in the liver. We found a significant induction of the expression of the basolateral efflux transporters Mrp3 and Mrp4 and canalicular transporter Mdr1 in rats treated with swertianlarin, compared with the controls (1.9-fold and 2.2-fold, P < 0.005, and 3.4-fold, P < 0.05, respectively). The expression of detoxification enzymes Cyp3a, Ugt2b, Sult2a1 and Gsta1 in rats treated with swertianlarin was significantly higher than that in controls (3.7-fold, 2.8-fold, 2.1-fold, and 1.7-fold, respectively, all P < 0.05). Expression of the synthetic enzyme, Cyp8b1, was higher in rats treated with swertianlarin than that in controls (1.8-fold at mRNA level and 3.4-flod at protein level, P < 0.05). Elevated serum levels of the conjugated bile acids, taurocholic acid and taurodeoxycholic acid, and a reduction in levels of serum ALP, unconjugated bile acid αMCA, and TG were observed (all P < 0.05). In conclusion, swertianlarin significantly up-regulates hepatic bile acid detoxification enzymes and efflux transporters in rats, which can increase the water solubility of hydrophobic bile acids and elimination of conjugated bile acids. PMID:25755705

  19. Zn2+-induced changes at the root level account for the increased tolerance of acclimated tobacco plants

    PubMed Central

    Bazihizina, Nadia; Taiti, Cosimo; Marti, Lucia; Rodrigo-Moreno, Ana; Spinelli, Francesco; Giordano, Cristiana; Caparrotta, Stefania; Gori, Massimo; Azzarello, Elisa; Mancuso, Stefano

    2014-01-01

    Evidence suggests that heavy-metal tolerance can be induced in plants following pre-treatment with non-toxic metal concentrations, but the results are still controversial. In the present study, tobacco plants were exposed to increasing Zn2+ concentrations (up to 250 and/or 500 μM ZnSO4) with or without a 1-week acclimation period with 30 μM ZnSO4. Elevated Zn2+ was highly toxic for plants, and after 3 weeks of treatments there was a marked (≥50%) decline in plant growth in non-acclimated plants. Plant acclimation, on the other hand, increased plant dry mass and leaf area up to 1.6-fold compared with non-acclimated ones. In non-acclimated plants, the addition of 250 μM ZnSO4 led to transient membrane depolarization and stomatal closure within 24h from the addition of the stress; by contrast, the acclimation process was associated with an improved stomatal regulation and a superior ability to maintain a negative root membrane potential, with values on average 37% more negative compared with non-acclimated plants. The different response at the plasma-membrane level between acclimated and non-acclimated plants was associated with an enhanced vacuolar Zn2+ sequestration and up to 2-fold higher expression of the tobacco orthologue of the Arabidopsis thaliana MTP1 gene. Thus, the acclimation process elicited specific detoxification mechanisms in roots that enhanced Zn2+ compartmentalization in vacuoles, thereby improving root membrane functionality and stomatal regulation in leaves following elevated Zn2+ stress. PMID:24928985

  20. Association of Cry1Ac Toxin Resistance in Helicoverpa zea (Boddie) with Increased Alkaline Phosphatase Levels in the Midgut Lumen

    PubMed Central

    Caccia, Silvia; Moar, William J.; Chandrashekhar, Jayadevi; Oppert, Cris; Anilkumar, Konasale J.; Jurat-Fuentes, Juan Luis

    2012-01-01

    Resistance to Bacillus thuringiensis Cry1Ac toxin was characterized in a population of Helicoverpa zea larvae previously shown not to have an alteration in toxin binding as the primary resistance mechanism to this toxin. Cry1Ac-selected larvae (AR1) were resistant to protoxins and toxins of Cry1Ab, Cry1Ac, and the corresponding modified proteins lacking helix α-1 (Cry1AbMod and Cry1AcMod). When comparing brush border membrane vesicles (BBMVs) prepared from susceptible (LC) and AR1 larval midguts, there were only negligible differences in overall Cry1Ac toxin binding, though AR1 had 18% reversible binding, in contrast to LC, in which all binding was irreversible. However, no differences were detected in Cry1Ac-induced pore formation activity in BBMVs from both strains. Enzymatic activities of two putative Cry1Ac receptors (aminopeptidase N [APN] and alkaline phosphatase [ALP]) were significantly reduced (2-fold and 3-fold, respectively) in BBMVs from AR1 compared to LC larvae. These reductions corresponded to reduced protein levels in midgut luminal contents only in the case of ALP, with an almost 10-fold increase in specific ALP activity in midgut fluids from AR1 compared to LC larvae. Partially purified H. zea ALP bound Cry1Ac toxin in ligand blots and competed with Cry1Ac toxin for BBMV binding. Based on these results, we suggest the existence of at least one mechanism of resistance to Cry1A toxins in H. zea involving binding of Cry1Ac toxin to an ALP receptor in the larval midgut lumen of resistant larvae. PMID:22685140

  1. Association of Cry1Ac toxin resistance in Helicoverpa zea (Boddie) with increased alkaline phosphatase levels in the midgut lumen.

    PubMed

    Caccia, Silvia; Moar, William J; Chandrashekhar, Jayadevi; Oppert, Cris; Anilkumar, Konasale J; Jurat-Fuentes, Juan Luis; Ferré, Juan

    2012-08-01

    Resistance to Bacillus thuringiensis Cry1Ac toxin was characterized in a population of Helicoverpa zea larvae previously shown not to have an alteration in toxin binding as the primary resistance mechanism to this toxin. Cry1Ac-selected larvae (AR1) were resistant to protoxins and toxins of Cry1Ab, Cry1Ac, and the corresponding modified proteins lacking helix α-1 (Cry1AbMod and Cry1AcMod). When comparing brush border membrane vesicles (BBMVs) prepared from susceptible (LC) and AR1 larval midguts, there were only negligible differences in overall Cry1Ac toxin binding, though AR1 had 18% reversible binding, in contrast to LC, in which all binding was irreversible. However, no differences were detected in Cry1Ac-induced pore formation activity in BBMVs from both strains. Enzymatic activities of two putative Cry1Ac receptors (aminopeptidase N [APN] and alkaline phosphatase [ALP]) were significantly reduced (2-fold and 3-fold, respectively) in BBMVs from AR1 compared to LC larvae. These reductions corresponded to reduced protein levels in midgut luminal contents only in the case of ALP, with an almost 10-fold increase in specific ALP activity in midgut fluids from AR1 compared to LC larvae. Partially purified H. zea ALP bound Cry1Ac toxin in ligand blots and competed with Cry1Ac toxin for BBMV binding. Based on these results, we suggest the existence of at least one mechanism of resistance to Cry1A toxins in H. zea involving binding of Cry1Ac toxin to an ALP receptor in the larval midgut lumen of resistant larvae. PMID:22685140

  2. A comparative multidimensional LC-MS proteomic analysis reveals mechanisms for furan aldehyde detoxification in Thermoanaerobacter pseudethanolicus 39E

    DOE PAGES

    Clarkson, Sonya M.; Hamilton-Brehm, Scott D.; Giannone, Richard J.; Engle, Nancy L.; Tschaplinski, Timothy J.; Hettich, Robert L.; Elkins, James G.

    2014-12-03

    Background: Chemical and physical pretreatment of lignocellulosic biomass improves substrate reactivity for increased microbial biofuel production, but also restricts growth via the release of furan aldehydes such as furfural and 5-hydroxymethylfurfural (5-HMF). The physiological effects of these inhibitors on thermophilic, fermentative bacteria is important to understand; especially as cellulolytic strains are being developed for consolidated bioprocessing (CBP) of lignocellulosic feedstocks. Identifying mechanisms for detoxification of aldehydes in naturally resistant strains such as Thermoanaerobacter spp. may also enable improvements in candidate CBP microorganisms. Results: T. pseudethanolicus 39E, an anaerobic, saccharolytic thermophile, was found to grow readily in the presence of 30more » mM furfural and 20 mM 5-HMF and reduce these aldehydes to their respective alcohols in situ. The proteomes of T. pseudethanolicus 39E grown in the presence or absence of 15 mM furfural were compared to identify upregulated enzymes potentially responsible for the observed reduction. A total of 225 proteins were differentially regulated in response to the 15 mM furfural treatment with 152 upregulated vs. 73 downregulated. Only 86 proteins exhibited a 2-fold change in abundance in either direction. Of these, 53 were upregulated in the presence of furfural and 33 were downregulated. Two oxidoreductases were upregulated at least 2-fold by furfural and were targeted for further investigation: Teth39_1597, encodes a predicted butanol dehydrogenase (BdhA) and Teth39_1598, a predicted aldo/keto reductase (AKR). Both genes were cloned from T. pseudethanolicus 39E, with the respective enzymes overexpressed in E. coli and specific activities determined against a variety of aldehydes. BdhA showed significant activity with all aldehydes tested, including furfural and 5-HMF, using NADPH as the cofactor. AKR also showed significant activity with NADPH, but only with four carbon butyr

  3. Elimination of hydrogenase active site assembly blocks H2 production and increases ethanol yield in Clostridium thermocellum

    SciTech Connect

    Biswas, Ranjita; Zheng, Tianyong; Olson, Daniel G.; Lynd, Lee R.; Guss, Adam M.

    2015-02-01

    The native ability of Clostridium thermocellum to rapidly consume cellulose and produce ethanol makes it a leading candidate for a consolidated bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes lactate, formate, acetate, H2, and amino acids that compete with ethanol production for carbon and electrons. Elimination of H2 production could redirect carbon flux towards ethanol production by making more electrons available for acetyl-CoA reduction to ethanol. C. thermocellum encodes four hydrogenases and rather than delete each individually, we targeted a hydrogenase maturase gene (hydG), involved in converting the three [FeFe] hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe] hydrogenase (ech) resulted in a mutant that functionally lacks all four hydrogenases. H2 production in hydG ech was undetectable and ethanol yield increased nearly 2-fold compared to wild type. Interestingly, mutant growth improved upon the addition of acetate, which led to increased expression of genes related to sulfate metabolism, suggesting these mutants may use sulfate as a terminal electron acceptor to balance redox reactions. Genomic analysis of hydG revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH-dependent alcohol dehydrogenase activities. While this same adhE mutation is found in ethanol tolerant C. thermocellum strain E50C, hydG and hydG ech are not more ethanol tolerant than wild type, illustrating the complicated interactions between redox balancing and ethanol tolerance in C. thermocellum. The dramatic increase in ethanol production here suggests that targeting protein post-translational modification is a promising new approach for inactivation of multiple enzymes simultaneously for metabolic engineering.

  4. Elimination of hydrogenase active site assembly blocks H2 production and increases ethanol yield in Clostridium thermocellum

    DOE PAGES

    Biswas, Ranjita; Zheng, Tianyong; Olson, Daniel G.; Lynd, Lee R.; Guss, Adam M.

    2015-02-01

    The native ability of Clostridium thermocellum to rapidly consume cellulose and produce ethanol makes it a leading candidate for a consolidated bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes lactate, formate, acetate, H2, and amino acids that compete with ethanol production for carbon and electrons. Elimination of H2 production could redirect carbon flux towards ethanol production by making more electrons available for acetyl-CoA reduction to ethanol. C. thermocellum encodes four hydrogenases and rather than delete each individually, we targeted a hydrogenase maturase gene (hydG), involved in converting the three [FeFe] hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe]more » hydrogenase (ech) resulted in a mutant that functionally lacks all four hydrogenases. H2 production in hydG ech was undetectable and ethanol yield increased nearly 2-fold compared to wild type. Interestingly, mutant growth improved upon the addition of acetate, which led to increased expression of genes related to sulfate metabolism, suggesting these mutants may use sulfate as a terminal electron acceptor to balance redox reactions. Genomic analysis of hydG revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH-dependent alcohol dehydrogenase activities. While this same adhE mutation is found in ethanol tolerant C. thermocellum strain E50C, hydG and hydG ech are not more ethanol tolerant than wild type, illustrating the complicated interactions between redox balancing and ethanol tolerance in C. thermocellum. The dramatic increase in ethanol production here suggests that targeting protein post-translational modification is a promising new approach for inactivation of multiple enzymes simultaneously for metabolic engineering.« less

  5. Gut Balance, a synbiotic supplement, increases fecal Lactobacillus paracasei but has little effect on immunity in healthy physically active individuals

    PubMed Central

    West, Nicholas P.; Pyne, David B.; Cripps, Allan; Christophersen, Claus T.; Conlon, Michael A.; Fricker, Peter A.

    2012-01-01

    Synbiotic supplements, which contain multiple functional ingredients, may enhance the immune system more than the use of individual ingredients alone. A double blind active controlled parallel trial over a 21 day exercise training period was conducted to evaluate the effect of Gut BalanceTM, which contains Lactobacillus paracasei subsp paracasei (L. casei 431®), Bifidobacterium animalis ssp lactis (BB-12®), Lactobacillus acidophilus (LA-5®), Lactobacillus rhamnosus (LGG®), two prebiotics (raftiline and raftilose) and bovine whey derived lactoferrin and immunoglobulins with acacia gum on fecal microbiota, short chain fatty acids (SCFA), gut permeability, salivary lactoferrin and serum cytokines. All subjects randomized were included in the analysis. There was a 9-fold (1.2-fold to 64-fold; 95% confidence intervals p = 0.03) greater increase in fecal L. paracasei numbers with Gut BalanceTM compared with acacia gum supplementation. Gut BalanceTM was associated with a 50% (-12% to 72%; p = 0.02) smaller increase in the concentration of serum IL-16 in comparison to acacia gum from pre- to post-study. No substantial effects of either supplement were evident in fecal SCFA concentrations, measures of mucosal immunity or GI permeability. Clinical studies are now required to determine whether Gut BalanceTM may exert beneficial GI health effects by increasing the recovery of fecal L. paracasei. Both supplements had little effect on immunity. Twenty-two healthy physically active male subjects (mean age = 33.9 ± 6.5 y) were randomly allocated to either daily prebiotic or synbiotic supplementation for 21 day. Saliva, blood, urine and fecal samples were collected pre-, mid- and post-intervention. Participants recorded patterns of physical activity on a self-reported questionnaire. PMID:22572834

  6. Gut Balance, a synbiotic supplement, increases fecal Lactobacillus paracasei but has little effect on immunity in healthy physically active individuals.

    PubMed

    West, Nicholas P; Pyne, David B; Cripps, Allan W; Christophersen, Claus T; Conlon, Michael A; Fricker, Peter A

    2012-01-01

    Synbiotic supplements, which contain multiple functional ingredients, may enhance the immune system more than the use of individual ingredients alone. A double blind active controlled parallel trial over a 21 d exercise training period was conducted to evaluate the effect of Gut Balance™, which contains Lactobacillus paracasei subsp. paracasei (L. casei 431®), Bifidobacterium animalis ssp. lactis (BB-12®), Lactobacillus acidophilus (LA-5®), Lactobacillus rhamnosus (LGG®), two prebiotics (raftiline and raftilose) and bovine whey derived lactoferrin and immunoglobulins with acacia gum on fecal microbiota, short chain fatty acids (SCFA), gut permeability, salivary lactoferrin and serum cytokines. All subjects randomized were included in the analysis. There was a 9-fold (1.2-fold to 64-fold; 95% confidence intervals p = 0.03) greater increase in fecal L. paracasei numbers with Gut Balance™ compared with acacia gum supplementation. Gut Balance™ was associated with a 50% (-12% to 72%; p = 0.02) smaller increase in the concentration of serum IL-16 in comparison to acacia gum from pre- to post-study. No substantial effects of either supplement were evident in fecal SCFA concentrations, measures of mucosal immunity or GI permeability. Clinical studies are now required to determine whether Gut Balance™ may exert beneficial GI health effects by increasing the recovery of fecal L. paracasei. Both supplements had little effect on immunity. Twenty two healthy physically active male subjects (mean age = 33.9 ± 6.5y) were randomly allocated to either daily prebiotic or synbiotic supplementation for 21 d. Saliva, blood, urine and fecal samples were collected pre-, mid and post-intervention. Participants recorded patterns of physical activity on a self-reported questionnaire.

  7. Locating the Optic Nerve in Retinal Images: Comparing Model-Based and Bayesian Decision Methods

    SciTech Connect

    Karnowski, Thomas Paul; Tobin Jr, Kenneth William; Muthusamy Govindasamy, Vijaya Priya; Chaum, Edward

    2006-01-01

    In this work we compare two methods for automatic optic nerve (ON) localization in retinal imagery. The first method uses a Bayesian decision theory is criminator based on four spatial features of the retina imagery. The second method uses a principal component-based reconstruction to model the ON. We report on an improvement to the model-based technique by incorporating linear discriminant analysis and Bayesian decision theory methods. We explore a method to combine both techniques to produce a composite technique with high accuracy and rapid throughput. Results are shown for a data set of 395 images with 2-fold validation testing.

  8. Elaidate, an 18-Carbon Trans-monoenoic Fatty Acid, but not Physiological Fatty Acids Increases Intracellular Zn2+ in Human Macrophages

    PubMed Central

    Zacherl, Janelle R.; Tourkova, Irina; St Croix, Claudette M.; Robinson, Lisa J.; Peck Palmer, Octavia M.; Mihalik, Stephanie J.; Blair, Harry C.

    2015-01-01

    Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 minute treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 hours. To determine longer term effects of trans fatty acids, we compared whole exome mRNA expression of (trans) elaidate to (cis) oleate, 30 μM, at 44 hours in human macrophages. We found that elaidate changed Zn2+-homeostasis gene mRNAs markedly. This might be important because Zn2+ is a major regulator of macrophage activity. Messenger RNAs of seven Zn2+-binding metallothioneins decreased 2–4 fold; the zinc importer SLC39A10 increased 2-fold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn2+-homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 hours. Further, intracellular Zn2+ was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl)amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 hours, only cells treated with elaidate had increased Zn2+. The durable effect of elaidate on Zn2+ activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism. PMID:25358453

  9. Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction.

    PubMed

    Voorhees, Andrew P; DeLeon-Pennell, Kristine Y; Ma, Yonggang; Halade, Ganesh V; Yabluchanskiy, Andriy; Iyer, Rugmani Padmanabhan; Flynn, Elizabeth; Cates, Courtney A; Lindsey, Merry L; Han, Hai-Chao

    2015-08-01

    Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9(-/-) showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9(-/-) infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9(-/-) infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9(-/-) infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.

  10. Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness.

    PubMed

    Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R

    2013-10-01

    Variations in the expression levels of the dopamine transporter (DAT) can influence responsiveness to psychostimulant drugs like cocaine. To better understand this relationship, we studied a new DAT-low expresser (DAT-LE) mouse model and performed behavioral and biochemical studies with it. Immunoblotting and [(3) H]WIN 35,428 binding analyses revealed that these mice express ∼35% of wildtype (WT) mouse striatal DAT levels. Compared to WT mice, DAT-LE mice were hyperactive in a novel open-field environment. Despite their higher basal locomotor activity, cocaine (10 or 20 mg/kg, i.p.) induced greater locomotor activation in DAT-LE mice than in WT mice. The maximal velocity (Vmax ) of DAT-mediated [(3) H]DA uptake into striatal synaptosomes was reduced by 46% in DAT-LE mice, as compared to WT. Overall, considering the reduced number of DAT binding sites (Bmax ) along with the reduced Vmax in DAT-LE mice, a 2-fold increase in DA uptake turnover rate (Vmax /Bmax ) was found, relative to WT mice. This suggests that neuroadaptive changes have occurred in the DAT-LE mice that would help to compensate for their low DAT numbers. Interestingly, these changes do not include a reduction in tyrosine hydroxylase levels, as was previously reported in DAT knockout homozygous and heterozygous animals. Further, these changes are not sufficient to prevent elevated novelty- and cocaine-induced locomotor activity. Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression. PMID:23564231

  11. Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness.

    PubMed

    Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R

    2013-10-01

    Variations in the expression levels of the dopamine transporter (DAT) can influence responsiveness to psychostimulant drugs like cocaine. To better understand this relationship, we studied a new DAT-low expresser (DAT-LE) mouse model and performed behavioral and biochemical studies with it. Immunoblotting and [(3) H]WIN 35,428 binding analyses revealed that these mice express ∼35% of wildtype (WT) mouse striatal DAT levels. Compared to WT mice, DAT-LE mice were hyperactive in a novel open-field environment. Despite their higher basal locomotor activity, cocaine (10 or 20 mg/kg, i.p.) induced greater locomotor activation in DAT-LE mice than in WT mice. The maximal velocity (Vmax ) of DAT-mediated [(3) H]DA uptake into striatal synaptosomes was reduced by 46% in DAT-LE mice, as compared to WT. Overall, considering the reduced number of DAT binding sites (Bmax ) along with the reduced Vmax in DAT-LE mice, a 2-fold increase in DA uptake turnover rate (Vmax /Bmax ) was found, relative to WT mice. This suggests that neuroadaptive changes have occurred in the DAT-LE mice that would help to compensate for their low DAT numbers. Interestingly, these changes do not include a reduction in tyrosine hydroxylase levels, as was previously reported in DAT knockout homozygous and heterozygous animals. Further, these changes are not sufficient to prevent elevated novelty- and cocaine-induced locomotor activity. Hence, these mice represent a unique model for studying changes of in vivo DAT function and regulation that result from markedly reduced levels of DAT expression.

  12. Comparative analysis of envelope proteomes in Escherichia coli B and K-12 strains.

    PubMed

    Han, Mee-Jung; Lee, Sang Yup; Hong, Soon Ho

    2012-04-01

    Recent genome comparisons of E. coli B and K-12 strains have indicated that the makeup of the cell envelopes in these two strains is quite different. Therefore, we analyzed and compared the envelope proteomes of E. coli BL21(DE3) and MG1655. A total of 165 protein spots, including 62 nonredundant proteins, were unambiguously identified by two-dimensional gel electrophoresis and mass spectrometry. Of these, 43 proteins were conserved between the two strains, whereas 4 and 16 strain-specific proteins were identified only in E. coli BL21(DE3) and MG1655, respectively. Additionally, 24 proteins showed more than 2-fold differences in intensities between the B and K-12 strains. The reference envelope proteome maps showed that E. coli envelope mainly contained channel proteins and lipoproteins. Interesting proteomic observations between the two strains were as follows: (i) B produced more OmpF porin with a larger pore size than K-12, indicating an increase in the membrane permeability; (ii) B produced higher amounts of lipoproteins, which facilitates the assembly of outer membrane beta-barrel proteins; and (iii) motility- (FliC) and chemotaxis-related proteins (CheA and CheW) were detected only in K-12, which showed that E. coli B is restricted with regard to migration under unfavorable conditions. These differences may influence the permeability and integrity of the cell envelope, showing that E. coli B may be more susceptible than K-12 to certain stress conditions. Thus, these findings suggest that E. coli K-12 and its derivatives will be more favorable strains in certain biotechnological applications, such as cell surface display or membrane engineering studies.

  13. Comparative analysis of envelope proteomes in Escherichia coli B and K-12 strains.

    PubMed

    Han, Mee-Jung; Lee, Sang Yup; Hong, Soon Ho

    2012-04-01

    Recent genome comparisons of E. coli B and K-12 strains have indicated that the makeup of the cell envelopes in these two strains is quite different. Therefore, we analyzed and compared the envelope proteomes of E. coli BL21(DE3) and MG1655. A total of 165 protein spots, including 62 nonredundant proteins, were unambiguously identified by two-dimensional gel electrophoresis and mass spectrometry. Of these, 43 proteins were conserved between the two strains, whereas 4 and 16 strain-specific proteins were identified only in E. coli BL21(DE3) and MG1655, respectively. Additionally, 24 proteins showed more than 2-fold differences in intensities between the B and K-12 strains. The reference envelope proteome maps showed that E. coli envelope mainly contained channel proteins and lipoproteins. Interesting proteomic observations between the two strains were as follows: (i) B produced more OmpF porin with a larger pore size than K-12, indicating an increase in the membrane permeability; (ii) B produced higher amounts of lipoproteins, which facilitates the assembly of outer membrane beta-barrel proteins; and (iii) motility- (FliC) and chemotaxis-related proteins (CheA and CheW) were detected only in K-12, which showed that E. coli B is restricted with regard to migration under unfavorable conditions. These differences may influence the permeability and integrity of the cell envelope, showing that E. coli B may be more susceptible than K-12 to certain stress conditions. Thus, these findings suggest that E. coli K-12 and its derivatives will be more favorable strains in certain biotechnological applications, such as cell surface display or membrane engineering studies. PMID:22534293

  14. Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation

    PubMed Central

    Orriss, Isabel R.; Arnett, Timothy R.; George, Jacob; Witham, Miles D.

    2016-01-01

    Allopurinol and its active metabolite, oxypurinol are widely used in the treatment of gout and hyperuricemia. They inhibit xanthine oxidase (XO) an enzyme in the purine degradation pathway that converts xanthine to uric acid. This investigation examined the effect of allopurinol and oxypurinol on bone formation, cell number and viability, gene expression and enzyme activity in differentiating and mature, bone-forming osteoblasts. Although mRNA expression remained relatively constant, XO activity decreased over time with mature osteoblasts displaying reduced levels of uric acid (20% decrease). Treatment with allopurinol and oxypurinol (0.1–1 µM) reduced XO activity by up to 30%. At these concentrations, allopurinol and oxypurinol increased bone formation by osteoblasts ~4-fold and ~3-fold, respectively. Cell number and viability were unaffected. Both drugs increased tissue non-specific alkaline phosphatase (TNAP) activity up to 65%. Osteocalcin and TNAP mRNA expression was increased, 5-fold and 2-fold, respectively. Expression of NPP1, the enzyme responsible for generating the mineralisation inhibitor, pyrophosphate, was decreased 5-fold. Col1α1 mRNA expression and soluble collagen levels were unchanged. Osteoclast formation and resorptive activity were not affected by treatment with allopurinol or oxypurinol. Our data suggest that inhibition of XO activity promotes osteoblast differentiation, leading to increased bone formation in vitro. PMID:26968635

  15. The transcription of MGAT4A glycosyl transferase is increased in white cells of peripheral blood of Type 2 Diabetes patients

    PubMed Central

    López-Orduña, Eduardo; Cruz, Miguel; García-Mena, Jaime

    2007-01-01

    Background Human glycosylase IV is involved in GLUT2 transporter regulation in pancreatic β cells. A KO of this gene along with a high fat diet in a mice model has been associated with the development of type 2 diabetes (T2D). The aims of this study were to measure and compare the MGAT4A mRNA levels in white blood cells (WBC) from T2D subjects and healthy subjects (T2NB), and to measure the half-life of the MGAT4A mRNA. Results We studied a sample of 73 individuals, 40 T2D subjects and 33 T2NB subjects. Anthropometrical and biochemical profiles were registered. The MGAT4A mRNA levels in WBC and the transcript half-life in Jurkat T cells were determined by Real-Time PCR. A blood differential cell counting was made for each individual. Cell counting showed T2D subjects exhibited an increased number of WBC compared to T2NB subjects (P = 0.0001). Biochemical parameters such as fasting glucose (P = 0.0001), and triglycerides (P = 0.002) were statistically significant. T2D subjects had 4.2-fold more MGAT4A transcript compared to T2NB subjects (P = 0.002). The MGAT4A mRNA had a half-life of 2.04 h in Jurkat T cells. Conclusion The results of this work suggest that in T2D subjects, high levels of glucose and triglycerides are accompanied by an increase on MGAT4A mRNA levels and WBC count; condition that suggests a pro-inflammatory state due to a chronic metabolic stress. PMID:17953760

  16. China update: HIV increasing.

    PubMed

    Gil, V E

    1993-01-01

    The HIV/AIDS case rate in China increased 117% over the period 1990-1992, from 446 to 957 HIV infections. While the majority of cases in 1990 were localized in Yunnan among minority farmers and manual laborers, infection is now found in 19 provinces, counties, and urban areas over a wider spectrum of society. The concentration of cases among IV-drug users has decreased from 83.4% to 72.6%. HIV monitoring and prevention stations have been in place in the country since 1986. The government also encouraged special zones and semiautonomous cities as well as the World Health Organization to take steps to monitor and prevent the spread of HIV. While these effort have served to augment the degree of sex education previously provided, low budgets, bureaucracy, and ambivalence have impeded control efforts. Only 1.25 million of the 1.16 billion population has been serosampled over 8 years and 100,000 fewer serosamples were taken in 1992 compared to in 1991. Neither the general population nor health workers have sufficient knowledge about HIV/AIDS to prevent its continued spread. While gay men sampled in Beijing were better informed about transmission means and risk groups, over two thirds believed they were not at risk if they avoided having sex with foreigners. Recent economic reform measures allowing large movements of population from rural to urban areas, increased disposable income available for prostitutes, and greater exposure to alternative sexual norms and behaviors through the media and music further increase the risk of HIV transmission, especially among the younger generation. To counter these risks, an AIDS hotline for information and referrals has been established in Beijing which openly reaches out to the homosexual community and fields 8-12 calls/day. Training programs for doctors, counselors, professors, and social workers have been attended by people from more than 30 provinces and regions. In addition, modest research into sexual behavior is also being

  17. The Selective Loss of the Type 2 Iodothyronine Deiodinase in Mouse Thyrotrophs Increases Basal TSH but Blunts the Thyrotropin Response to Hypothyroidism

    PubMed Central

    Luongo, Cristina; Martin, Cecilia; Vella, Kristen; Marsili, Alessandro; Ambrosio, Raffaele; Dentice, Monica; Harney, John W.; Salvatore, Domenico; Zavacki, Ann Marie

    2015-01-01

    The type 2 iodothyronine deiodinase (D2) is essential for feedback regulation of TSH by T4. We genetically inactivated in vivo D2 in thyrotrophs using a mouse model of Cga-driven cre recombinase. Pituitary D2 activity was reduced 90% in the Cga-cre D2 knockout (KO) mice compared with control Dio2fl/fl mice. There was no growth or reproductive phenotype. Basal TSH levels were increased 1.5- to 1.8-fold, but serum T4 and T3 were not different from the controls in adult mice. In hypothyroid adult mice, suppression of TSH by T4, but not T3, was impaired. Despite mild basal TSH elevation, the TSH increase in response to hypothyroidism was 4-fold reduced in the Cga-cre D2KO compared with control mice despite an identical level of pituitary TSH α- and β-subunit mRNAs. In neonatal Cga-cre D2KO mice, TSH was also 2-fold higher than in the controls, but serum T4 was elevated. Despite a constant TSH, serum T4 increased 2–3-fold between postnatal day (P) 5 and P15 in both genotypes. The pituitary, but not cerebrocortical, D2 activity was markedly elevated in P5 mice decreasing towards adult levels by P17. In conclusion, a congenital severe reduction of thyrotroph D2 causes a major impairment of the TSH response to hypothyroidism. This would be deleterious to the compensatory adaptation of the thyroid gland to iodine deficiency. PMID:25456070

  18. Managing Vancouver B1 fractures by cerclage system compared to locking plate fixation - a biomechanical study.

    PubMed

    Gordon, Katharina; Winkler, Martin; Hofstädter, Thomas; Dorn, Ulrich; Augat, Peter

    2016-06-01

    With increasing life expectancy and number of total hip arthroplasties (THA), the need for revision surgery is increasing too. The aim of this study was to evaluate the optimal fracture treatment for a clinically characteristic Vancouver B1 fracture. We hypothesized that locking plate fixation has biomechanical advantages over fixation with a simple cerclage system. Additionally, we hypothesized that removal of the primary short stem and revision with a long stem would show biomechanical benefit. The biomechanical testing was performed with a static and a dynamic loading protocol on twenty 4th Generation sawbones. These were divided into four different groups (n = 5 each). In group 1, the primary uncemented short stem remained and the fracture was stabilized with a locking plate. In group 2, the primary stem remained and the fracture was stabilized with a cerclage stabilization system containing two stabilizers and four cerclages. In group 3, the primary stem was replaced by an uncemented long revision stem and the fracture was fixed with a locking plate. In group 4, the short stem was replaced by a long revision stem and the fracture was fixed with the cerclage system. Static testing revealed that the revision of the short stem with the long stem caused a 2-fold (p < 0.001, ANOVA) increase of axial stiffness. In dynamic testing, the number of cycles to failure was 4 times (p < 0.001, ANOVA) higher with the long revision stem. Compared to locked plating cerclage wiring demonstrated a 26% more cycles to failure (p = 0.031, ANOVA). The load to failure was 91% larger (p < 0.001, ANOVA) with the long revision stem and 11% smaller with locked plating (p < 0.001, ANOVA). In conclusion, the present biomechanical study indicates that periprosthetic Vancouver B1 fractures can be sufficiently fixed by simple cerclage systems. Revision with a long replacement stem provides a superior mechanical stability regardless of type of osteosynthesis fixation and is therefore a viable

  19. Comparative genotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by a flow cytometric in vitro micronucleus assay.

    PubMed

    Sahu, Saura C; Njoroge, Joyce; Bryce, Steven M; Yourick, Jeffrey J; Sprando, Robert L

    2014-11-01

    Two widely used in vitro cell culture models, human liver HepG2 cells and human colon Caco2 cells, and flow cytometry techniques were evaluated as tools for rapid screening of potential genotoxicity of food-related nanosilver. Comparative genotoxic potential of 20 nm silver was evaluated in HepG2 and Caco2 cell cultures by a flow cytometric-based in vitro micronucleus assay. The nanosilver, characterized by the dynamic light scattering, transmission electron microscopy and inductively coupled plasma-mass spectrometry analysis, showed no agglomeration of the silver nanoparticles. The inductively coupled plasma-mass spectrometry and transmission electron microscopy analysis demonstrated the uptake of 20 nm silver by both cell types. The 20 nm silver exposure of HepG2 cells increased the concentration-dependent micronucleus formation sevenfold at 10 µg ml(-1) concentration in attached cell conditions and 1.3-fold in cell suspension conditions compared to the vehicle controls. However, compared to the vehicle controls, the 20 nm silver exposure of Caco2 cells increased the micronucleus formation 1.2-fold at a concentration of 10 µg ml(-1) both in the attached cell conditions as well as in the cell suspension conditions. Our results of flow cytometric in vitro micronucleus assay appear to suggest that the HepG2 cells are more susceptible to the nanosilver-induced micronucleus formation than the Caco2 cells compared to the vehicle controls. However, our results also suggest that the widely used in vitro models, HepG2 and Caco2 cells and the flow cytometric in vitro micronucleus assay are valuable tools for the rapid screening of genotoxic potential of nanosilver and deserve more careful evaluation.

  20. Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio.

    PubMed Central

    Navab, M; Hama-Levy, S; Van Lenten, B J; Fonarow, G C; Cardinez, C J; Castellani, L W; Brennan, M L; Lusis, A J; Fogelman, A M; La Du, B N

    1997-01-01

    We have examined the effects of mildly oxidized LDL and atherosclerosis on the levels of two proteins associated with HDL; apolipoprotein J (apoJ), and paraoxonase (PON). On an atherogenic diet, PON activity decreased by 52%, and apoJ levels increased 2.8-fold in fatty streak susceptible mice, C57BL/6J (BL/6), but not in fatty streak resistant mice, C3H/HeJ (C3H). Plasma PON activity was also significantly decreased, and apoJ levels were markedly increased in apolipoprotein E knockout mice on the chow diet, resulting in a 9.2-fold increase in the apoJ/PON ratio as compared to controls. Furthermore, a dramatic increase in the apoJ/PON ratio (over 100-fold) was observed in LDL receptor knockout mice when they were fed a 0.15%-cholesterol-enriched diet. Injection of mildly oxidized LDL (but not native LDL) into BL/6 mice (but not in C3H mice) on a chow diet resulted in a 59% decrease in PON activity (P < 0.01) and a 3.6-fold increase in apoJ levels (P < 0.01). When an acute phase reaction was induced in rabbits, or the rabbits were placed on an atherogenic diet, hepatic mRNA for apoJ was increased by 2.7-fold and 2.8-fold, respectively. Treatment of HepG2 cells in culture with mildly oxidized LDL (but not native LDL) resulted in reduced mRNA levels for PON (3.0-fold decrease) and increased mRNA levels for apoJ (2.0-fold increase). In normolipidemic patients with angiographically documented coronary artery disease who did not have diabetes and were not on lipid-lowering medication (n = 14), the total cholesterol/HDL cholesterol ratio was 3.1+/-0.9 as compared to 2.9+/-0.4 in the controls (n = 19). This difference was not statistically significant. In contrast, the apoJ/PON ratio was 3.0+/-0.4 in the patients compared to 0.72+/-0.2 in the controls (P < 0.009). In a subset of these normolipidemic patients (n = 5), the PON activity was low (48+/-6.6 versus 98+/-17 U/ml for controls; P < 0.009), despite similar normal HDL levels, and the HDL from these patients failed to

  1. Angiotensin-converting enzyme and matrix metalloproteinase inhibition with developing heart failure: comparative effects on left ventricular function and geometry

    NASA Technical Reports Server (NTRS)

    McElmurray, J. H. 3rd; Mukherjee, R.; New, R. B.; Sampson, A. C.; King, M. K.; Hendrick, J. W.; Goldberg, A.; Peterson, T. J.; Hallak, H.; Zile, M. R.; Spinale, F. G.

    1999-01-01

    The progression of congestive heart failure (CHF) is left ventricular (LV) myocardial remodeling. The matrix metalloproteinases (MMPs) contribute to tissue remodeling and therefore MMP inhibition may serve as a useful therapeutic target in CHF. Angiotensin converting enzyme (ACE) inhibition favorably affects LV myocardial remodeling in CHF. This study examined the effects of specific MMP inhibition, ACE inhibition, and combined treatment on LV systolic and diastolic function in a model of CHF. Pigs were randomly assigned to five groups: 1) rapid atrial pacing (240 beats/min) for 3 weeks (n = 8); 2) ACE inhibition (fosinopril, 2.5 mg/kg b.i.d. orally) and rapid pacing (n = 8); 3) MMP inhibition (PD166793 2 mg/kg/day p.o.) and rapid pacing (n = 8); 4) combined ACE and MMP inhibition (2.5 mg/kg b.i.d. and 2 mg/kg/day, respectively) and rapid pacing (n = 8); and 5) controls (n = 9). LV peak wall stress increased by 2-fold with rapid pacing and was reduced in all treatment groups. LV fractional shortening fell by nearly 2-fold with rapid pacing and increased in all treatment groups. The circumferential fiber shortening-systolic stress relation was reduced with rapid pacing and increased in the ACE inhibition and combination groups. LV myocardial stiffness constant was unchanged in the rapid pacing group, increased nearly 2-fold in the MMP inhibition group, and was normalized in the ACE inhibition and combination treatment groups. Increased MMP activation contributes to the LV dilation and increased wall stress with pacing CHF and a contributory downstream mechanism of ACE inhibition is an effect on MMP activity.

  2. Emergency contraception: increasing public awareness.

    PubMed

    2003-02-01

    This article begins by addressing misperceptions that emergency contraception is something new and untested or inherently unsafe, and that it is comparable to an abortion. It then describes efforts that are underway to increase awareness among consumers and health care providers alike.

  3. Increase of Eicosapentaenoic Acid in Thraustochytrids through Thraustochytrid Ubiquitin Promoter-Driven Expression of a Fatty Acid Δ5 Desaturase Gene▿†

    PubMed Central

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-01-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C16:0), n − 6 docosapentaenoic acid (DPA) (C22:5n − 6), and docosahexaenoic acid (DHA) (C22:6n − 3), with eicosapentaenoic acid (EPA) (C20:5n − 3) and arachidonic acid (AA) (C20:4n − 6) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C20:4n − 3) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C20:3n − 6) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  4. NOD promoter-controlled AtIRT1 expression functions synergistically with NAS and FERRITIN genes to increase iron in rice grains.

    PubMed

    Boonyaves, Kulaporn; Gruissem, Wilhelm; Bhullar, Navreet K

    2016-02-01

    Rice is a staple food for over half of the world's population, but it contains only low amounts of bioavailable micronutrients for human nutrition. Consequently, micronutrient deficiency is a widespread health problem among people who depend primarily on rice as their staple food. Iron deficiency anemia is one of the most serious forms of malnutrition. Biofortification of rice grains for increased iron content is an effective strategy to reduce iron deficiency. Unlike other grass species, rice takes up iron as Fe(II) via the IRON REGULATED TRANSPORTER (IRT) in addition to Fe(III)-phytosiderophore chelates. We expressed Arabidopsis IRT1 (AtIRT1) under control of the Medicago sativa EARLY NODULIN 12B promoter in our previously developed high-iron NFP rice lines expressing NICOTIANAMINE SYNTHASE (AtNAS1) and FERRITIN. Transgenic rice lines expressing AtIRT1 alone had significant increases in iron and combined with NAS and FERRITIN increased iron to 9.6 µg/g DW in the polished grains that is 2.2-fold higher as compared to NFP lines. The grains of AtIRT1 lines also accumulated more copper and zinc but not manganese. Our results demonstrate that the concerted expression of AtIRT1, AtNAS1 and PvFERRITIN synergistically increases iron in both polished and unpolished rice grains. AtIRT1 is therefore a valuable transporter for iron biofortification programs when used in combination with other genes encoding iron transporters and/or storage proteins.

  5. Increase of eicosapentaenoic acid in thraustochytrids through thraustochytrid ubiquitin promoter-driven expression of a fatty acid {delta}5 desaturase gene.

    PubMed

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-06-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C(16:0)), n - 6 docosapentaenoic acid (DPA) (C(22:5)(n) (- 6)), and docosahexaenoic acid (DHA) (C(22:6)(n) (- 3)), with eicosapentaenoic acid (EPA) (C(20:5)(n) (- 3)) and arachidonic acid (AA) (C(20:4)(n) (- 6)) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C(20:4)(n) (- 3)) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C(20:3)(n) (- 6)) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs.

  6. Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model.

    PubMed

    Trifilieff, Alexandre; Ethell, Brian T; Sykes, David A; Watson, Kenny J; Collingwood, Steve; Charlton, Steven J; Kent, Toby C

    2015-08-15

    Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED50 values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1h; >200 fold at 6h) than with tiotropium (1.5 and 4.2 fold at 1h; 4.6 and 5.5 fold at 6h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M2 muscarinic receptor occupancy, which predicted significantly higher M2 receptor blockade at ED50 doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. PMID:26026369

  7. Increased O-GlcNAc Levels Correlate with Decreased O-GlcNAcase Levels in Alzheimer Disease Brain

    PubMed Central

    Förster, Sarah; Welleford, Andrew S.; Triplett, Judy C.; Sultana, Rukhsana; Schmitz, Brigitte; Butterfield, D. Allan

    2014-01-01

    The potential role of the posttranslational modification of proteins with O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O-GlcNAc levels in AD brain have produced inconsistent results and the reasons for altered O-GlcNAcylation in AD are still poorly understood. In this study, we show a 1.2 fold increase in cytosolic protein O-GlcNAc modification in AD brain when compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be attributable to differential modification of a few individual proteins. While our finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting results emphasize the need for further studies providing conclusive evidence on the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT protein levels are unaffected in AD, OGA protein levels are significantly decreased to 75 % of those in control samples. In addition, augmented protein O-GlcNAc modification correlates to decreased OGA protein levels in AD subjects. While OGA inhibitors are already being tested for AD treatment, our results provide a strong indication that the general subject of O-GlcNAcylation and specifically its regulation by OGA and OGT in AD need further investigation to conclusively elucidate its potential role in AD pathogenesis and treatment. PMID:24859566

  8. [Comparative S-adenosyl-L-methionine and S-adenosyl-L-homocysteine content in the tissues of experimental tumors in the process of their growth].

    PubMed

    Orlov, E N

    1980-01-01

    Content of S-adenosyl-l-methionine (SAM) in rat tissues of Pliss lymphosarcoma, of sarcoma 180 and in adenocarcinoma 755 of mice varied within the limits of 27-57 nM/g, 60-64 nM/g and 32-40 nM/g of wet tissue, respectively, content of S-adenosyl-l-homocysteine (SAH) varied in the tumors studied within the limits of 19-28, 16-21 and 11-20 nM/g, respectively. In the tumor bearing mice the content of SAM was unaltered in liver tissue during the growth of sarcoma 180 or adenocarcinoma 755. Development of Pliss lymphosarcoma in rats was accompanied by a decrease in content of SAM in liver tissue. When the rate of Pliss lymphosarcoma growth was decreased, the content of SAH in the tumor was unaltered but the level of SAM was decreased about 2-fold and the ratio SAH/SAM was increased, correspondingly, approximately 2-fold. If the rate of growth of mice adenocarcinoma 755 was elevated, content of SAM in the tumor was increased but the SAH level was markedly decreased and the ratio SAH/SAM was decreased about 2-fold. Concentrations of SAH and SAM were unaltered in mice sarcoma 180 with the linear rate of growth from 0.15 to 1.6 g. The data obtained suggest that the rate of growth of the tumors studied correlated with relative and absolute content of SAM and SAH.

  9. A comparative multidimensional LC-MS proteomic analysis reveals mechanisms for furan aldehyde detoxification in Thermoanaerobacter pseudethanolicus 39E

    SciTech Connect

    Clarkson, Sonya M.; Hamilton-Brehm, Scott D.; Giannone, Richard J.; Engle, Nancy L.; Tschaplinski, Timothy J.; Hettich, Robert L.; Elkins, James G.

    2014-12-03

    Background: Chemical and physical pretreatment of lignocellulosic biomass improves substrate reactivity for increased microbial biofuel production, but also restricts growth via the release of furan aldehydes such as furfural and 5-hydroxymethylfurfural (5-HMF). The physiological effects of these inhibitors on thermophilic, fermentative bacteria is important to understand; especially as cellulolytic strains are being developed for consolidated bioprocessing (CBP) of lignocellulosic feedstocks. Identifying mechanisms for detoxification of aldehydes in naturally resistant strains such as Thermoanaerobacter spp. may also enable improvements in candidate CBP microorganisms. Results: T. pseudethanolicus 39E, an anaerobic, saccharolytic thermophile, was found to grow readily in the presence of 30 mM furfural and 20 mM 5-HMF and reduce these aldehydes to their respective alcohols in situ. The proteomes of T. pseudethanolicus 39E grown in the presence or absence of 15 mM furfural were compared to identify upregulated enzymes potentially responsible for the observed reduction. A total of 225 proteins were differentially regulated in response to the 15 mM furfural treatment with 152 upregulated vs. 73 downregulated. Only 86 proteins exhibited a 2-fold change in abundance in either direction. Of these, 53 were upregulated in the presence of furfural and 33 were downregulated. Two oxidoreductases were upregulated at least 2-fold by furfural and were targeted for further investigation: Teth39_1597, encodes a predicted butanol dehydrogenase (BdhA) and Teth39_1598, a predicted aldo/keto reductase (AKR). Both genes were cloned from T. pseudethanolicus 39E, with the respective enzymes overexpressed in E. coli and specific activities determined against a variety of aldehydes. BdhA showed significant activity with all aldehydes tested, including furfural and 5-HMF, using NADPH as the cofactor. AKR also showed significant activity with NADPH

  10. Rate of pull-out strength gain of dual-etched titanium implants: a comparative study in rabbits.

    PubMed

    Baker, D; London, R M; O'Neal, R

    1999-01-01

    The purpose of this study was to investigate the rate of pull-out strength gain of an etched titanium implant surface. Rabbit tibiae were used to compare machined titanium and proprietary dual-etched titanium implants. Two custom cylindric implants (3 mm in diameter and 4 mm in length) were placed in each right anteromedial tibia in 31 rabbits. At weeks 1, 2, 3, 4, 5, and 8, the implants in 5 rabbits were subjected to failure shear loading in a pull-out test. For shear failure testing, each tibial segment was mounted in a precision alignment jig, and an Instron pull-out test was performed on each implant. Beginning at week 3, there was a statistically significant difference (P < .01) between the dual-etched and the machined implants. There was a significant increase in strength for dual-etched implants between week 5 and week 8, while the machined implants did not show an increase during this time interval. The etched implants maintained a significantly greater pull-out strength for the remainder of the study, with a 3.2-fold greater mean strength at 8 weeks, equivalent to 6 months in humans. At 3 weeks, the etched implant's strength exceeded the strength that the machined implant had achieved at 8 weeks. In short-term healing in the rabbit tibia, the dual-etched surface demonstrated a more rapid rate of pull-out strength gain than the machined surface and remained significantly stronger throughout the 8 weeks of the study. PMID:10531744

  11. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    PubMed

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J

    2010-01-01

    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  12. Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

    PubMed Central

    Ripplinger, Crystal M.; Li, Wenwen; Hadley, Jennifer; Chen, Junjie; Rothenberg, Florence; Lombardi, Raffaella; Wickline, Samuel A.; Marian, Ali J.; Efimov, Igor R.

    2008-01-01

    Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (β-myosin heavy chain–Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n = 6) and wild-type (WT) rabbits (n = 6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3 ± 2.1 versus 7.4 ± 2.3 V/cm; P = 3.2e−5), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6 ± 10.9° versus 79.2 ± 7.8°; P = 0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46 ± 2.44% versus 2.68 ± 0.77%; P = 0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy. PMID:17885214

  13. Increased intracranial pressure

    MedlinePlus

    ... rupture and subarachnoid hemorrhage Brain tumor Encephalitis Head injury Hydrocephalus (increased fluid around the brain) Hypertensive brain hemorrhage Intraventricular hemorrhage Meningitis Subdural hematoma Status epilepticus Stroke

  14. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

    NASA Astrophysics Data System (ADS)

    Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  15. A mixed-effects Statistical Model for Comparative LC-MS Proteomics Studies

    SciTech Connect

    Daly, Don S.; Anderson, Kevin K.; Panisko, Ellen A.; Purvine, Samuel O.; Fang, Ruihua; Monroe, Matthew E.; Baker, Scott E.

    2008-03-01

    Comparing a protein’s concentrations across two or more treatments is the focus of many proteomics studies. A frequent source of measurements for these comparisons is a mass spectrometry (MS) analysis of a protein’s peptide ions separated by liquid chromatography (LC) following its enzymatic digestion. Alas, LC-MS identification and quantification of equimolar peptides can vary significantly due to their unequal digestion, separation and ionization. This unequal measurability of peptides, the largest source of LC-MS nuisance variation, stymies confident comparison of a protein’s concentration across treatments. Our objective is to introduce a mixed-effects statistical model for comparative LC-MS proteomics studies. We describe LC-MS peptide abundance with a linear model featuring pivotal terms that account for unequal peptide LC-MS measurability. We advance fitting this model to an often incomplete LC-MS dataset with REstricted Maximum Likelihood (REML) estimation, producing estimates of model goodness-offit, treatment effects, standard errors, confidence intervals, and protein relative concentrations. We illustrate the model with an experiment featuring a known dilution series of a filamentous ascomycete fungus Trichoderma reesei protein mixture. For the 781 of 1546 T.reesei proteins with sufficient data coverage, the fitted mixed-effects models capably described the LC-MS measurements. The LC-MS measurability terms effectively accounted for this major source of uncertainty. Ninety percent of the relative concentration estimates were within 1/2 fold of the true relative concentrations. Akin to the common ratio method, this model also produced biased estimates, albeit less biased. Bias decreased significantly, both absolutely and relative to the ratio method, as the number of observed peptides per protein increased. Mixed-effects statistical modeling offers a flexible, well-established methodology for comparative proteomics studies integrating common

  16. Increased brain uptake and oxidation of acetate in heavy drinkers.

    PubMed

    Jiang, Lihong; Gulanski, Barbara Irene; De Feyter, Henk M; Weinzimer, Stuart A; Pittman, Brian; Guidone, Elizabeth; Koretski, Julia; Harman, Susan; Petrakis, Ismene L; Krystal, John H; Mason, Graeme F

    2013-04-01

    When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. This study used 13C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-13C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13C abundance of N-acetylaspartate (NAA) and the appearance of 13C-labeled glutamate, glutamine, and acetate. Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial. PMID:23478412

  17. Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

    2014-06-01

    Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

  18. Increasing hygiene productivity.

    PubMed

    Levin, Roger P

    2003-03-01

    Dentists have many opportunities to expand the role of dental hygienists and provide patients with better oral health care, while increasing production and profits. But the proper business systems and verbal skills need to be incorporated. You must train hygienists to do all they can do for every patient. Begin with one service and add others, as the hygienists becomes familiar with each one. Set a goal of a 15% increase in production per year for the hygiene department. Clinicians using these strategies have experienced as much as a 100% to 200% increase in hygiene revenue during the first year of incorporating these services. An added benefit is that these dentists often see a substantial increase in dental treatment diagnosis and case acceptance. An effective and efficient hygiene department will often identify and help secure more than 50% of a doctor's production.

  19. Increasing productivity: Another approach

    SciTech Connect

    Norton, F.J.

    1996-06-10

    An engineering information (EI) and information technology (IT) organization that must improve its productivity should work to further its business goals. This paper explores a comprehensive model for increasing EI/IT productivity by supporting organizational objectives.

  20. Increasing Public Library Productivity.

    ERIC Educational Resources Information Center

    Samuelson, Howard

    1981-01-01

    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  1. Increases in Problem Drinking

    MedlinePlus

    ... review our exit disclaimer . Subscribe Increases in Problem Drinking Alcohol use disorder is becoming more common, a ... the need to better educate people about problem drinking and its treatment. Alcohol use disorder, or AUD, ...

  2. Increased thymidylate synthase in L1210 cells possessing acquired resistance to N10-propargyl-5,8-dideazafolic acid (CB3717): development, characterization, and cross-resistance studies

    SciTech Connect

    Jackman, A.L.; Alison, D.L.; Calvert, A.H.; Harrap, K.R.

    1986-06-01

    The properties are described of a mutant L1210 cell line (L1210:C15) with acquired resistance (greater than 200-fold) to the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid. TS was overproduced 45-fold and was accompanied by a small increase in the activity of dihydrofolate reductase (2.6-fold). Both the level of resistance and enzyme activities were maintained in drug-free medium (greater than 300 generations). Failure of N10-propargyl-5,8-dideazafolic acid to suppress the (/sup 3/H)-2'-deoxyuridine incorporation into the acid-precipitable material of the resistant line supported the evidence that TS overproduction was the mechanism of resistance; consequently the L1210:C15 cells were largely cross-resistant to another (but weaker) TS inhibitor, 5,8-dideazafolic acid. Minimal cross-resistance was observed to the dihydrofolate reductase inhibitors methotrexate and 5-methyl-5,8-dideazaaminopterin (5- and 2-fold, respectively). L1210 and L1210:C15 cells were, however, equally sensitive to 5-fluorodeoxyuridine (FdUrd), an unexpected finding since a metabolite, 5-fluorodeoxyuridine monophosphate, is a potent TS inhibitor; however, this cytotoxicity against the L1210:C15 cells was antagonized by coincubation with 5 microM folinic acid although folinic acid potentiated the cytotoxicity of FdUrd to the N10-propargyl-5,8-dideazafolic acid-sensitive L1210 line. Thymidine was much less effective as a FdUrd protecting agent in the L1210:C15 when compared with the L1210 cells; however, a combination of thymidine plus hypoxanthine was without any additional effect (compared with thymidine alone) against the sensitive line but effectively protected L1210:C15 cells.

  3. Bilateral Differences in Muscle Architecture and Increased Rate of Injury in National Basketball Association Players

    PubMed Central

    Mangine, Gerald T.; Hoffman, Jay R.; Gonzalez, Adam M.; Jajtner, Adam R.; Scanlon, Tyler; Rogowski, Joseph P.; Wells, Adam J.; Fragala, Maren S.; Stout, Jeffrey R.

    2014-01-01

    Context Professional basketball players have demanding schedules that, in combination with certain underlying physical characteristics and side-to-side strength and power imbalances, may make them vulnerable to lower extremity injuries. Objective To examine the relationship among skeletal muscle architecture, lower body power, and games missed because of lower extremity injury (%MISS) in professional basketball players. Design Cross-sectional study. Setting Human Performance Laboratory. Patients or Other Participants Nine players under contract for Orlando Magic were assessed. We compared athletes who were injured (n = 4, height = 203.2 ± 5.5 cm, mass = 105 ± 7.5 kg, age = 25.0 ± 2.8 years) and those who remained healthy (n = 5, height = 200.2 ± 12.2 cm, mass = 100.1 ± 16.6 kg, age = 22.4 ± 1.9 years) during the season. Main Outcome Measure(s) Bilateral ultrasonographic measurements of muscle thickness, pennation angle, echo intensity, and cross-sectional area of the rectus femoris and vastus lateralis were collected before regular-season play. Subsequently, muscle thickness and pennation angle were used to compute fascicle length. Along with unilateral jumping power, inferences were made upon the magnitude of the relationship between the percentage bilateral difference in these measures and %MISS, as well as between injured and healthy athletes. Results The data indicated likely relationships between %MISS and age (r = 0.772), and between %MISS and bilateral differences in rectus femoris cross-sectional area (7.8% ± 6.4%; r = 0.657) and vastus lateralis cross-sectional area (6.2% ± 4.8%; r = 0.521), as well as a possible relationship with vastus lateralis muscle thickness (7.9% ± 8.9%; r = 0.444). Echo-intensity differences in the vastus lateralis were greater in injured (8.0% ± 2.4%) versus healthy athletes (3.2% ± 2.0%). Although a 2-fold difference in mean jumping power was observed between injured (26.3 ± 14.9 W) and healthy athletes (13.6 ± 8.7 W

  4. Hydrologic effects of increased urbanization

    USGS Publications Warehouse

    Guay, Joel R.

    1995-01-01

    Urban areas in Perris Valley, California, have more than tripled during the last 20 years, resulting in increased storm-runoff volumes and peak discharges. To quantify the effects of increased urbanization, rainfall-runoff models of the basin were developed to simulate runoff for 1970-75 and 1990-93 conditions. Hourly rainfall data for 1949-93 were used with the rainfall-runoff models to simulate a long-term record of storm runoff. The hydrologic effects of increased urbanization from 1970-75 to 1990-93 conditions were analyzed by comparing the frequency of annual peak discharges and runoff volumes, and a duration analysis of storm peak discharges. The maximum annual-peak discharge for the 1990-93 model simulation was 32 percent higher than the discharge for 1970-75 model simulation. However, the frequency analysis of each time series indicated the 100-year peak discharges for each study period were identical.

  5. Alzheimer's Disease and Non-Demented High Pathology Control Nonagenarians: Comparing and Contrasting the Biochemistry of Cognitively Successful Aging

    PubMed Central

    Maarouf, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Walker, Douglas G.; Hunter, Jesse M.; Kruchowsky, Jane C.; Woltjer, Randy; Kaye, Jeffrey; Castaño, Eduardo M.; Sabbagh, Marwan N.; Beach, Thomas G.; Roher, Alex E.

    2011-01-01

    The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND)-HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Aβ/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Aβ40, Aβ42 and tau were quantified by ELISA. Interestingly, only Aβ42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti-angiogenic pigment epithelium derived factor levels were lower. The lack of clear Aβ-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must

  6. Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

    PubMed Central

    Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

    2015-01-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

  7. Characterization and comparative analysis of psychrophilic and mesophilic alpha-amylases from Euplotes species: a contribution to the understanding of enzyme thermal adaptation.

    PubMed

    Yang, Guang; Yang, Guang; Aprile, Lino; Turturo, Vincenzo; Pucciarelli, Sandra; Pucciarelli, Stefania; Miceli, Cristina

    2013-09-01

    The eukaryotic α-amylase isolated from the psychrophilic ciliated protozoon Euplotes focardii (EfAmy) was expressed in Escherichia coli and biochemically characterized. Its enzymatic activity was compared to that of the homologous protein from the mesophilic congeneric species Euplotes crassus (EcAmy). The comparison of the amino acid composition and the surface residue composition of the two enzymes indicated a preference for tiny residues and the avoidance of charged, aromatic and hydrophobic residues in EfAmy. Our comparative homology modeling study reveals a lack of surface salt bridges, a decreased number of the surface charged residues, decreased hydrogen bonds and bound ions, and a reduction of aromatic-sulfur interactions, cationic-π interactions and disulfide interactions in EfAmy. In contrast, sequence alignment and homology modeling showed five unconserved prolines located on the surface loops of EcAmy. By analyzing amylolytic activity towards soluble starch as the substrate, we determined the temperature and pH dependence, thermostability and kinetic parameters of these two enzymes. We demonstrated that EfAmy shows the characteristics of a psychrophilic α-amylase, such as the highest hydrolytic activity at low temperatures and high thermolability. In contrast, the EcAmy showed mesophilic characteristics with the highest activity at moderate temperatures and a more than 2-fold increased half-life at 50°C compared to EfAmy. The kcat and KM values of EfAmy were higher than those of the mesophilic EcAmy at all tested temperatures. Furthermore, both EfAmy and EcAmy showed maximum activities at pH 9 and maintained high activities in the presence of surfactants. These results suggest the potential applications of EfAmy and EcAmy as ingredients in detergents for industrial applications.

  8. Fibrin gels exhibit improved biological, structural, and mechanical properties compared with collagen gels in cell-based tendon tissue-engineered constructs.

    PubMed

    Breidenbach, Andrew P; Dyment, Nathaniel A; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T; Rowe, David W; Kadler, Karl E; Butler, David L

    2015-02-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair.

  9. Prodigiosin isolated from cell wall of Serratia marcescens alters expression of apoptosis-related genes and increases apoptosis in colorectal cancer cells.

    PubMed

    Hassankhani, Ramin; Sam, Mohammad Reza; Esmaeilou, Mohammad; Ahangar, Prinaz

    2015-01-01

    Colorectal cancer remains often refractory to classic therapies. In consequence, the search for new anti-tumor agents with minimal toxicity is of particular interest in colon cancer treatment. Prodigiosin as a secondary metabolite of Serratia marcescens induces apoptosis in various kinds of cancer cells with low toxicity on normal cells. In the present study, we evaluated the effect of prodigiosin on proliferation and expression of apoptotic-related genes in HT-29 cells. Malignant cells were treated to various concentrations of prodigiosin and proliferation rate, survivin, Bcl-2, Bax and Bad mRNA levels, caspase 3 activation and apoptosis were evaluated by different cellular and molecular techniques. Treatment of cells with increasing concentration of prodigiosin decreased significantly cell proliferation in a dose- and time-dependent manner. Following 48-h treatment, growth rate was measured to be 77 ± 6.8, 41.3 ± 3.1 and 46 ± 6.3 % for 100, 400 and 600 nM prodigiosin, respectively, compared to untreated cells. This molecule induced 61.7, 90 and 89 % decrease in survivin mRNA level as well as 1.9-, 2.8- and 2.2-fold increase in caspase 3 activation for indicated concentrations of prodigiosin, respectively. The level of Bcl-2 mRNA was inversely proportional to Bax and Bad mRNA levels. Low mRNA levels of Bcl-2 combined with high levels of Bax and Bad mRNAs were correlated to higher apoptosis rate in treated cells. Our data suggest that prodigiosin-induced apoptosis may ascribe to Bcl-2 and survivin inhibition in HT-29 cells and these genes may provide promising molecular targets of prodigiosin. Collectively, prodigiosin may have a great potential for colorectal cancer-directed therapy.

  10. Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

    PubMed Central

    Boles, Julie L; Ross, Michael G; Beloosesky, Ron; Desai, Mina; Belkacemi, Louiza

    2012-01-01

    Background: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4) pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages. Methods: Preterm (e16) or near-term (e20) placental explants from pregnant rats were treated with 0, 1, or 10 μg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB) protein expression levels were determined by Western blot analysis. Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus vehicle). Conversely, interleukin-6 release from e20 explants was not significantly different compared with vehicle, and tumor necrosis alpha release was only 2-fold higher (P < 0.05 versus vehicle) following exposure to lipopolysaccharide. Phosphorylated NFκB protein expression was significantly increased in the nuclear fraction from placental explants exposed to lipopolysaccharide at both e16 and e

  11. Seismic waves increase permeability.

    PubMed

    Elkhoury, Jean E; Brodsky, Emily E; Agnew, Duncan C

    2006-06-29

    Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Piñon Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults.

  12. Colloidal Dispersions for the Delivery of Acyclovir: A Comparative Study

    PubMed Central

    Cortesi, Rita; Ravani, Laura; Menegatti, Enea; Drechsler, M.; Esposito, Elisabetta

    2011-01-01

    This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells. PMID:23112407

  13. Colloidal dispersions for the delivery of acyclovir: a comparative study.

    PubMed

    Cortesi, Rita; Ravani, Laura; Menegatti, Enea; Drechsler, M; Esposito, Elisabetta

    2011-11-01

    This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells. PMID:23112407

  14. Colloidal dispersions for the delivery of acyclovir: a comparative study.

    PubMed

    Cortesi, Rita; Ravani, Laura; Menegatti, Enea; Drechsler, M; Esposito, Elisabetta

    2011-11-01

    This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells.

  15. Increased global financings

    SciTech Connect

    Anderson, J.

    1994-10-01

    The results of a financial rankings survey for the first half of 1994 show increased financial activity over the second half of 1993. More than $10.5 billion is reported by developers and financial firms for 62 transactions during 1994`s first six months.

  16. Productivity increases in science

    SciTech Connect

    Danko, J.E.; Young, J.K.; Molton, P.M.; Dirks, J.A.

    1993-02-01

    The study quantifies the impact on the cost of experimentation of synergistic advancements in instrumentation, theory, and computation over the last two decades. The study finds that the productivity of experimental investigation (experimental results/$) is increasing as science is transformed from a linear, isolated approach to a hierarchical, multidisciplinary approach. Developments such as massively parallel processors coupled with instrumental systems with multiple probes and diverse data analysis capabilities will further this transformation and increase the productivity of scientific studies. The complexities and scale of today`s scientific challenges are much greater than in the past, however, so that the costs of research are increasing. Even though science is much more productive in terms of the experimental results, the challenges facing scientific investigators are increasing at an even faster pace. New approaches to infrastructure investments must capitalize on the changing dynamics of research and allow the scientific community to maximize gains in productivity so that complex problems can be attacked cost-effectively. Research strategies that include user facilities and coordinated experimental, computational, and theoretical research are needed.

  17. Productivity increases in science

    SciTech Connect

    Danko, J.E.; Young, J.K.; Molton, P.M.; Dirks, J.A.

    1993-02-01

    The study quantifies the impact on the cost of experimentation of synergistic advancements in instrumentation, theory, and computation over the last two decades. The study finds that the productivity of experimental investigation (experimental results/$) is increasing as science is transformed from a linear, isolated approach to a hierarchical, multidisciplinary approach. Developments such as massively parallel processors coupled with instrumental systems with multiple probes and diverse data analysis capabilities will further this transformation and increase the productivity of scientific studies. The complexities and scale of today's scientific challenges are much greater than in the past, however, so that the costs of research are increasing. Even though science is much more productive in terms of the experimental results, the challenges facing scientific investigators are increasing at an even faster pace. New approaches to infrastructure investments must capitalize on the changing dynamics of research and allow the scientific community to maximize gains in productivity so that complex problems can be attacked cost-effectively. Research strategies that include user facilities and coordinated experimental, computational, and theoretical research are needed.

  18. Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion

    PubMed Central

    Loupe, J M; Miller, P J; Bonner, B P; Maggi, E C; Vijayaraghavan, J; Crabtree, J S; Taylor, C M; Zabaleta, J; Hollenbach, A D

    2016-01-01

    Rhabdomyosarcoma, one of the most common childhood sarcomas, is comprised of two main subtypes, embryonal and alveolar (ARMS). ARMS, the more aggressive subtype, is primarily characterized by the t(2;13)(p35;p14) chromosomal translocation, which fuses two transcription factors, PAX3 and FOXO1 to generate the oncogenic fusion protein PAX3-FOXO1. Patients with PAX3-FOXO1-postitive tumors have a poor prognosis, in part due to the enhanced local invasive capacity of these cells, which leads to the increased metastatic potential for this tumor. Despite this knowledge, little is known about the role that the oncogenic fusion protein has in this increased invasive potential. In this report we use large-scale comparative transcriptomic analyses in physiologically relevant primary myoblasts to demonstrate that the presence of PAX3-FOXO1 is sufficient to alter the expression of 70 mRNA and 27 miRNA in a manner predicted to promote cellular invasion. In contrast the expression of PAX3 alters 60 mRNA and 23 miRNA in a manner predicted to inhibit invasion. We demonstrate that these alterations in mRNA and miRNA translate into changes in the invasive potential of primary myoblasts with PAX3-FOXO1 increasing invasion nearly 2-fold while PAX3 decreases invasion nearly 4-fold. Taken together, these results allow us to build off of previous reports and develop a more expansive molecular model by which the presence of PAX3-FOXO1 alters global gene regulatory networks to enhance the local invasiveness of cells. Further, the global nature of our observed changes highlights the fact that instead of focusing on a single-gene target, we must develop multi-faceted treatment regimens targeting multiple genes of a single oncogenic phenotype or multiple genes that target different oncogenic phenotypes for tumor progression. PMID:27454080

  19. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage.

    PubMed

    Cevc, Gregor; Blume, Gabriele

    2004-05-27

    We characterised biological properties of novel formulations of two low-potency glucocorticosteroids, dexamethasone and hydrocortisone, which have an equivalent dose ratio of 1:50 in vasoconstriction tests. The rate of such carrier-mediated, mainly non-diffusive glucocorticosteroids transport with very deformable lipid vesicles (Transfersomes) through the skin, and the corresponding cutaneous drug biodistribution data, were complemented with the drug bio-efficacy studies. The minimum effective drug dose that reduces arachidonic acid-induced murine ear oedema by 50% was used as one bioactivity indicator. The minimum drug amount ensuring such an effect in mouse skin decreases appreciably when a corticosteroid is applied epicutaneously with very deformable vesicles rather than a lotion or a crème. Specifically, the minimum effective dose for hydrocortisone in very deformable carriers is 2-3 microg cm(-2) whereas for the crème- or lotion-like preparations at least 10 microg cm(-2) is required. Such three- to fivefold relative increase of hydrocortisone potency is accompanied by at least 13%, and more often >20%, absolute drug potency enhancement. The delivery of hydrocortisone with very deformable carriers moreover prolongs the suppression of the drug-induced oedema nearly 2-fold (to approximately 24 h per application). The effective dose of dexamethasone delivered with very deformable vesicles into murine skin is reduced >10 times compared with the crème- or lotion-based products. Specifically, less than 0.1 microg cm(-2) dexamethasone in very deformable vesicles suppresses the arachidonic acid-induced murine ear oedema >50%, on the average. Dexamethasone use on the skin in such vesicles extends the duration of drug action fourfold, compared with a commercial crème, i.e. to >48 h per application. Epicutaneous use of glucocorticosteroids in very deformable vesicles also diminishes such drug's abrasion sensitivity and may increase the general robustness of drug

  20. Comparative toxicogenomic analysis of oral Cr(VI) exposure effects in rat and mouse small intestinal epithelia

    SciTech Connect

    Kopec, Anna K.; Thompson, Chad M.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.

    2012-07-15

    Continuous exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water results in intestinal tumors in mice but not rats. Concentration-dependent gene expression effects were evaluated in female F344 rat duodenal and jejunal epithelia following 7 and 90 days of exposure to 0.3–520 mg/L (as sodium dichromate dihydrate, SDD) in drinking water. Whole-genome microarrays identified 3269 and 1815 duodenal, and 4557 and 1534 jejunal differentially expressed genes at 8 and 91 days, respectively, with significant overlaps between the intestinal segments. Functional annotation identified gene expression changes associated with oxidative stress, cell cycle, cell death, and immune response that were consistent with reported changes in redox status and histopathology. Comparative analysis with B6C3F1 mouse data from a similarly designed study identified 2790 differentially expressed rat orthologs in the duodenum compared to 5013 mouse orthologs at day 8, and only 1504 rat and 3484 mouse orthologs at day 91. Automated dose–response modeling resulted in similar median EC{sub 50}s in the rodent duodenal and jejunal mucosae. Comparative examination of differentially expressed genes also identified divergently regulated orthologs. Comparable numbers of differentially expressed genes were observed at equivalent Cr concentrations (μg Cr/g duodenum). However, mice accumulated higher Cr levels than rats at ≥ 170 mg/L SDD, resulting in a ∼ 2-fold increase in the number of differentially expressed genes. These qualitative and quantitative differences in differential gene expression, which correlate with differences in tissue dose, likely contribute to the disparate intestinal tumor outcomes. -- Highlights: ► Cr(VI) elicits dose-dependent changes in gene expression in rat intestine. ► Cr(VI) elicits less differential gene expression in rats compared to mice. ► Cr(VI) gene expression can be phenotypically anchored to intestinal changes. ► Species

  1. Comparative interactomics: comparing apples and pears?

    PubMed

    Kiemer, Lars; Cesareni, Gianni

    2007-10-01

    The study of the complex web of interactions that link biological molecules in a cell is the subject of interactomics--currently one of the fastest moving fields in molecular biology. The recent completion of high-throughput studies to investigate systematically all the possible interactions in a variety of model organisms has provided unique opportunities to compare interaction networks and ask questions about their conservation during evolution. It is expected that this approach will yield a scientific return as rich as that obtained in the past decade from comparing genomes and proteomes from different organisms.

  2. Designer drilling increases recovery

    SciTech Connect

    Eck-Olsen, J.; Drevdal, K.E.

    1995-04-01

    Implementation of a new designer-well profile has resulted in increased recovery and production rates. The geologically complex Gullfaks field, located in the Norwegian sector of the North Sea, required a new type of well profile to increase total recovery and production rates from Gullfaks A, B and C platforms. Advances in steerable technology and directional drilling performance enabled a 3-D horizontal, extended-reach well profile, now designated as a designer well, to penetrate multiple targets. This article presents the concept, implementation and conclusions drawn from designer well application. Gullfaks field, in Norwegian North Sea Block 34/10, is the first license ever run by a fully Norwegian joint venture corporation. The license group consists of Statoil (operator), Norsk Hydro and Saga Petroleum. The field currently produces more than 535,000 bopd from three main Jurassic reservoirs.

  3. Revamps increase efficiency

    SciTech Connect

    Marschner, F.; Moertel, H.G.

    1986-01-01

    In many cases, idle capacities throughout the work and lack of financing capital forbid the construction of new chemical plants that are more profitable and reflect the latest state-of-the-art. On the other hand, the glut of cheap raw materials over the past 20 years led to the construction of numerous plants according to the motto, ''make it cheap-energy consumption is of secondary importance.'' Such projects included, above all, hydrogen plants based on natural gas and plants to produce syngases for methanol, ammonia and oxo alcohols. As raw materials are becoming scarcer almost everywhere in the work and raw material prices keep rising, taking such plants out of service in many instances can be avoided only by increasing their efficiency, sometimes by increasing their capacity (debottlenecking) or by revamping them to use cheaper feedstocks.

  4. High population increase rates.

    PubMed

    1991-09-01

    In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems. PMID:12284289

  5. Increase in family allowances.

    PubMed

    1989-01-01

    In July 1989 the family allowance structure in Australia was changed from a 4-rate to a 2-rate structure. The new rates were increased to $A9 a week for the 1st 3 children and $A12 for each additional child. The Family Allowance Supplment rate for children 13-15 years old was raised from $A31 to $A34.10/week. PMID:12344544

  6. Increasing student success

    NASA Astrophysics Data System (ADS)

    Stewart, Gay; Stewart, John

    2013-03-01

    A more scientifically literate society benefits all STEM disciplines, as well as society as a whole. It is best realized by better serving all undergraduate STEM students. In better-serving all students, a physics department also benefits. The University of Arkansas, Fayetteville physics department has seen a drastic change in number of majors, the number of students active in research and the number of graduates pursuing graduate work, while also increasing the number of majors who decide to teach. Prior to our involvement with the Physics Teacher Education Coalition, graduation rates had increased by more than a factor of 4 in 4 years. After the increased efforts when we became a part of PhysTEC (http://PhysTEC.org) our graduation numbers doubled again. Specific attention to class policy to impact student learning in our introductory courses and strong preparation of the graduate teaching assistants, and quality advising were our primary areas of emphasis. What worked to build these numbers and strengthen these resources at Arkansas will be discussed. This work was supported in part by the National Science Foundation and through the Physics Teacher Education Coalition.

  7. Condom use increasing.

    PubMed

    Finger, W R

    1998-01-01

    Condom use is central to the prevention of AIDS among people at risk for contracting HIV. As such, condom use is increasing dramatically even though many men say that they do not like using them. Condom sales through social marketing campaigns have increased dramatically in some countries, where tens of millions of condoms are sold annually. For example, during the period 1991-96, annual social marketing sales increased about five-fold in Ethiopia to 21 million, and nine-fold in Brazil to 27 million. These sales reflect the success of condom social marketing campaigns in making condoms accessible and largely affordable. There is also a greater general awareness of AIDS than there used to be, and communication campaigns have shown that condoms are an effective solution. More condoms still need to be used in the ongoing struggle against HIV/AIDS. The author discusses the factors which affect the limited acceptance of condoms, condom use outside of marriage, social marketing, and family planning programs. PMID:12293530

  8. Alarming increase in refugees.

    PubMed

    1992-01-01

    Over the past decade and half there has been an alarming worldwide increase in refugees. The total rose form 2.8 million in 1976 to 8.2 million in 1980, to 17.3 million in 1990. Africa's refugees rose from 1.2 million in 1976 to 5.6 million in 1990. Asia's increase over this period was much more rapid--from a mere 180,000 to 8 million. In the Americas the numbers more than trebled, from 770,000 to 2.7 million. Europe was the smallest increase, from 570,000 to 894,000. International law defines a refugee as someone outside of their own country, who has a well-founded fear of persecution because of their political or religious beliefs or ethnic origin, and who cannot turn to their own country for protection. Most refugees are genuine by this definition. The increase reflects, in part, fallout from the cold war. Ethiopia, Mozambique and Angola accounted for almost 1/2 of Africa's refugees; Afghanistan alone for 3/4 of Asia's total. They fled, for the most part, from 1 poor country into another, where they added to shortages of land and fuelwood, and intensified environmental pressure. Malawi, 1 of the poorest countries in the world, is sheltering perhaps as many as 750,000 refugees from the war in Mozambique. But among these refugees--especially among those who turned to the rich countries for asylum--were an increasing number of people who were not suffering political persecution. Driven out of their homes by the collapse of their environment or economic despair, and ready to take any means to get across borders, they are a new category: economic and environmental refugees. The most spectacular attempts hit the television screens: the Vietnamese boat people, ships festooned with Albanians. Behind the headlines there was a growing tide of asylum seekers. The numbers rose 10-fold in Germany from 1983 to 1990. In Switzerland they multiplied by 4 times. In Europe, as a whole, they grew from 71,000 in 1983 to an estimated 550,000 in 1990. In 1990 the numbers threatened to

  9. Lead exposure increases blood pressure by increasing angiotensinogen expression.

    PubMed

    Jiao, Jiandong; Wang, Miaomiao; Wang, Yiqing; Sun, Na; Li, Chunping

    2016-01-01

    Lead exposure can induce increased blood pressure. Several mechanisms have been proposed to explain lead-induced hypertension. Changes in angiotensinogen (AGT) expression levels or gene variants may also influence blood pressure. In this study, we hypothesized that AGT expression levels or gene variants contribute to lead-induced hypertension. A preliminary HEK293 cell model experiment was performed to analyze the association between AGT expression and lead exposure. In a population-based study, serum AGT level was measured in both lead-exposed and control populations. To further detect the influence of AGT gene single nucleotide polymorphisms (SNPs) in lead-induced hypertension, two SNPs (rs699 and rs4762) were genotyped in a case-control study including 219 lead-exposed subjects and 393 controls. Lead exposure caused an increase in AGT expression level in HEK 293 cell models (P < 0.001) compared to lead-free cells, and individuals exposed to lead had higher systolic and diastolic blood pressure (P < 0.001). Lead-exposed individuals had higher serum AGT levels compared to controls (P < 0.001). However, no association was found between AGT gene SNPs (rs699 and rs4762) and lead exposure. Nevertheless, the change in AGT expression level may play an important role in the development of lead-induced hypertension.

  10. Chinese Hamster Ovary (CHO) Host Cell Engineering to Increase Sialylation of Recombinant Therapeutic Proteins by Modulating Sialyltransferase Expression

    PubMed Central

    Lin, Nan; Mascarenhas, Joaquina; Sealover, Natalie R.; George, Henry J.; Brooks, Jeanne; Kayser, Kevin J.; Gau, Brian; Yasa, Isil; Azadi, Parastoo; Archer-Hartmann, Stephanie

    2015-01-01

    N-Glycans of human proteins possess both α2,6- and α2,3-linked terminal sialic acid (SA). Recombinant glycoproteins produced in Chinese hamster overy (CHO) only have α2,3-linkage due to the absence of α2,6-sialyltransferase (St6gal1) expression. The Chinese hamster ST6GAL1 was successfully overexpressed using a plasmid expression vector in three recombinant immunoglobulin G (IgG)-producing CHO cell lines. The stably transfected cell lines were enriched for ST6GAL1 overexpression using FITC-Sambucus nigra (SNA) lectin that preferentially binds α2,6-linked SA. The presence of α2,6-linked SA was confirmed using a novel LTQ Linear Ion Trap Mass Spectrometry (LTQ MS) method including MSn fragmentation in the enriched ST6GAL1 Clone 27. Furthermore, the total SA (mol/mol) in IgG produced by the enriched ST6GAL1 Clone 27 increased by 2-fold compared to the control. For host cell engineering, the CHOZN® GS host cell line was transfected and enriched for ST6GAL1 overexpression. Single-cell clones were derived from the enriched population and selected based on FITC-SNA staining and St6gal1 expression. Two clones (“ST6GAL1 OE Clone 31 and 32”) were confirmed for the presence of α2,6-linked SA in total host cell protein extracts. ST6GAL1 OE Clone 32 was subsequently used to express SAFC human IgG1. The recombinant IgG expressed in this host cell line was confirmed to have α2,6-linked SA and increased total SA content. In conclusion, overexpression of St6gal1 is sufficient to produce recombinant proteins with increased sialylation and more human-like glycoprofiles without combinatorial engineering of other sialylation pathway genes. This work represents our ongoing effort of glycoengineering in CHO host cell lines for the development of “bio-better” protein therapeutics and cell culture vaccine production. PMID:25641927

  11. Increasing Childhood Influenza Vaccination

    PubMed Central

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

    2014-01-01

    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  12. Operations dashboard: comparative study

    NASA Astrophysics Data System (ADS)

    Ramly, Noor Nashriq; Ismail, Ahmad Zuhairi; Aziz, Mohd Haris; Ahmad, Nurul Haszeli

    2011-10-01

    In this present days and age, there are increasing needs for companies to monitor application and infrastructure health. Apart from having proactive measures to secure their application and infrastructure, many see monitoring dashboards as crucial investment in disaster preparedness. As companies struggle to find the best solution to cater for their needs and interest for monitoring their application and infrastructure's health, this paper summarizes the studies made on several known off-the-shelf operations dashboard and in-house developed dashboard. A few criteria of good dashboard are collected from previous studies carried out by several researchers and rank them according to importance and business needs. The finalized criteria that will be discussed in later sections are data visualization, performance indicator, dashboard personalization, audit capability and alert/ notification. Comparative studies between several popular dashboards were then carried out to determine whether they met these criteria that we derived from the first exercise. The findings hopefully can be used to educate and provide an overview of selecting the best IT application and infrastructure operations dashboard that suit business needs, thus become the main contribution of this paper.

  13. Somatosensory loss increases vestibulospinal sensitivity.

    PubMed

    Horak, F B; Hlavacka, F

    2001-08-01

    To determine whether subjects with somatosensory loss show a compensatory increase in sensitivity to vestibular stimulation, we compared the amplitude of postural lean in response to four different intensities of bipolar galvanic stimulation in subjects with diabetic peripheral neuropathy (PNP) and age-matched control subjects. To determine whether healthy and neuropathic subjects show similar increases in sensitivity to galvanic vestibular stimulation when standing on unstable surfaces, both groups were exposed to galvanic stimulation while standing on a compliant foam surface. In these experiments, a 3-s pulse of galvanic current was administered to subjects standing with eyes closed and their heads turned toward one shoulder (anodal current on the forward mastoid). Anterior body tilt, as measured by center of foot pressure (CoP), increased proportionately with increasing galvanic vestibular stimulation intensity for all subjects. Subjects with peripheral neuropathy showed larger forward CoP displacement in response to galvanic stimulation than control subjects. The largest differences between neuropathy and control subjects were at the highest galvanic intensities, indicating an increased sensitivity to vestibular stimulation. Neuropathy subjects showed a larger increase in sensitivity to vestibular stimulation when standing on compliant foam than control subjects. The effect of galvanic stimulation was larger on the movement of the trunk segment in space than on the body's center of mass (CoM) angle, suggesting that the vestibular system acts to control trunk orientation rather than to control whole body posture. This study provides evidence for an increase in the sensitivity of the postural control system to vestibular stimulation when somatosensory information from the surface is disrupted either by peripheral neuropathy or by standing on an unstable surface. Simulations from a simple model of postural orientation incorporating feedback from the vestibular

  14. Core Noise - Increasing Importance

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart S.

    2011-01-01

    This presentation is a technical summary of and outlook for NASA-internal and NASA-sponsored external research on core (combustor and turbine) noise funded by the Fundamental Aeronautics Program Subsonic Fixed Wing (SFW) Project. Sections of the presentation cover: the SFW system-level noise metrics for the 2015, 2020, and 2025 timeframes; turbofan design trends and their aeroacoustic implications; the emerging importance of core noise and its relevance to the SFW Reduced-Perceived-Noise Technical Challenge; and the current research activities in the core-noise area, with additional details given about the development of a high-fidelity combustor-noise prediction capability as well as activities supporting the development of improved reduced-order, physics-based models for combustor-noise prediction. The need for benchmark data for validation of high-fidelity and modeling work and the value of a potential future diagnostic facility for testing of core-noise-reduction concepts are indicated. The NASA Fundamental Aeronautics Program has the principal objective of overcoming today's national challenges in air transportation. The SFW Reduced-Perceived-Noise Technical Challenge aims to develop concepts and technologies to dramatically reduce the perceived aircraft noise outside of airport boundaries. This reduction of aircraft noise is critical to enabling the anticipated large increase in future air traffic. Noise generated in the jet engine core, by sources such as the compressor, combustor, and turbine, can be a significant contribution to the overall noise signature at low-power conditions, typical of approach flight. At high engine power during takeoff, jet and fan noise have traditionally dominated over core noise. However, current design trends and expected technological advances in engine-cycle design as well as noise-reduction methods are likely to reduce non-core noise even at engine-power points higher than approach. In addition, future low-emission combustor

  15. Demyelination increases axonal stationary mitochondrial size and the speed of axonal mitochondrial transport

    PubMed Central

    Kiryu-Seo, Sumiko; Ohno, Nobuhiko; Kidd, Grahame J.; Komuro, Hitoshi; Trapp, Bruce D.

    2010-01-01

    Axonal degeneration contributes to permanent neurological disability in inherited and acquired diseases of myelin. Mitochondrial dysfunction has been proposed as a major contributor to this axonal degeneration. It remains to be determined, however, if myelination, demyelination or remyelination alter the size and distribution of axonal mitochondrial stationary sites or the rates of axonal mitochondrial transport. Using live myelinated rat dorsal root ganglion (DRG) cultures, we investigated whether myelination and lysolecithin-induced demyelination affect axonal mitochondria. Myelination increased the size of axonal stationary mitochondrial sites by 2.3 fold. Following demyelination, the size of axonal stationary mitochondrial sites was increased by an additional 2.2 fold and the transport velocity of motile mitochondria was increased by 47%. These measures returned to the levels of myelinated axons following remyelination. Demyelination induced activating transcription factor (ATF) 3 in DRG neurons. Knockdown of neuronal ATF3 by shRNA abolished the demyelination-induced increase in axonal mitochondrial transport and increased nitrotyrosine immunoreactivity in axonal mitochondria, suggesting that neuronal ATF3 expression and increased mitochondrial transport protect demyelinated axons from oxidative damage. In response to insufficient ATP production, demyelinated axons increase the size of stationary mitochondrial sites and thereby balance ATP production with the increased energy needs of nerve conduction. PMID:20463228

  16. Cloud computing for comparative genomics

    PubMed Central

    2010-01-01

    Background Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. Results We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. Conclusions The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems. PMID:20482786

  17. Elenoside increases intestinal motility

    PubMed Central

    Navarro, E; Alonso, SJ; Navarro, R; Trujillo, J; Jorge, E

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10-4, 6.4 x 10-4 and 1.2 x 10-3 mol/L, and cisapride at 10-6 mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain. PMID:17131476

  18. The Comparative Method Revisited.

    ERIC Educational Resources Information Center

    Sanford, Glenn M.; Lutterschmidt, William I.; Hutchison, Victor H.

    2002-01-01

    Describes the history of comparative methods and their use in biology as an investigative philosophy. Discusses Bernard's and Krogh's ideas and supports Jorgensen's arguments. Explains conceptual change in the comparative studies which is referred to as "comparative phylogenetic method". (Contains 33 references.) (YDS)

  19. Oral administration of D-alanine in monkeys robustly increases plasma and cerebrospinal fluid levels but experimental D-amino acid oxidase inhibitors had minimal effect.

    PubMed

    Rojas, Camilo; Alt, Jesse; Ator, Nancy A; Wilmoth, Heather; Rais, Rana; Hin, Niyada; DeVivo, Michael; Popiolek, Michael; Tsukamoto, Takashi; Slusher, Barbara S

    2016-09-01

    Hypofunction of the N-methyl-d-aspartate (NMDA) receptor is thought to exacerbate psychosis in patients diagnosed with schizophrenia. Consistent with this hypothesis, D-alanine, a co-agonist at the glycine site of the NMDA receptor, was shown to improve positive and cognitive symptoms when used as add-on therapy for schizophrenia treatment. However, D-alanine had to be administered at high doses (~7 g) to observe clinical effects. One possible reason for the high dose is that D-alanine could be undergoing oxidation by D-amino acid oxidase (DAAO) before it reaches the brain. If this is the case, the dose could be reduced by co-administration of D-alanine with a DAAO inhibitor (DAAOi). Early studies with rodents showed that co-administration of D-alanine with 5-chloro-benzo[d]isoxazol-3-ol (CBIO), a prototype DAAOi, significantly enhanced the levels of extracellular D-alanine in the frontal cortex compared with D-alanine alone. Further, the use of CBIO reduced the dose of D-alanine needed to attenuate prepulse inhibition deficits induced by dizocilpine. The objective of the work reported herein was to confirm the hypothesis that DAAO inhibition can enhance D-alanine exposure in a species closer to humans: non-human primates. We report that while oral D-alanine administration to baboons (10 mg/kg) enhanced D-alanine plasma and CSF levels over 20-fold versus endogenous levels, addition of experimental DAAOi to the regimen exhibited a 2.2-fold enhancement in plasma and no measurable effect on CSF levels. The results provide caution regarding the utility of DAAO inhibition to increase D-amino acid levels as treatment for patients with schizophrenia. PMID:27287825

  20. Catalyst increases COS conversion

    SciTech Connect

    Goodboy, K.P.

    1985-02-18

    Increasingly stringent air quality legislation is placing greater emphasis on conversion of COS and CS/sub 2/ in Claus plants for the maximum sulfur recovery. Overall sulfur recovery goals are dependent upon outstanding service from the Claus catalyst in each reactor because catalyst activity is a major factor influencing plant performance. Today's catalyst are much improved over those used 10 years ago for the Claus (H/sub 2/S/SO/sub 2/) reaction. Recent technical efforts have focused on the conversion of COS and CS/sub 2/. These carbon-sulfur compounds can account for as much as 50% of the sulfur going to the incinerator, which essentially converts all remaining sulfur species to SO/sub 2/ for atmospheric dispersion. Previously, the mechanism of Claus COS conversion, i.e., hydrolysis or oxidation by SO/sub 2/, was studied and the conclusion was that oxidation by SO/sub 2/ appears to be the predominate mode of COS conversion on sulfated alumina catalysts.

  1. Stress increases periodontal inflammation

    PubMed Central

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  2. What is comparable in comparative cognition?

    PubMed Central

    Chittka, Lars; Rossiter, Stephen J.; Skorupski, Peter; Fernando, Chrisantha

    2012-01-01

    To understand how complex, or ‘advanced’ various forms of cognition are, and to compare them between species for evolutionary studies, we need to understand the diversity of neural–computational mechanisms that may be involved, and to identify the genetic changes that are necessary to mediate changes in cognitive functions. The same overt cognitive capacity might be mediated by entirely different neural circuitries in different species, with a many-to-one mapping between behavioural routines, computations and their neural implementations. Comparative behavioural research needs to be complemented with a bottom-up approach in which neurobiological and molecular-genetic analyses allow pinpointing of underlying neural and genetic bases that constrain cognitive variation. Often, only very minor differences in circuitry might be needed to generate major shifts in cognitive functions and the possibility that cognitive traits arise by convergence or parallel evolution needs to be taken seriously. Hereditary variation in cognitive traits between individuals of a species might be extensive, and selection experiments on cognitive traits might be a useful avenue to explore how rapidly changes in cognitive abilities occur in the face of pertinent selection pressures. PMID:22927566

  3. An experimental increase in stuttering frequency.

    PubMed

    Martin, R R; Haroldson, S K

    1988-06-01

    The purpose of the present experiment was to investigate whether stuttering frequency could be increased from baseline by an experimental condition. Initially, 10 adult stutterers spoke spontaneously while alone. Next, they continued speaking, but with an adult, male conversationalist. Finally, the subjects again spoke while alone. Percent stuttering increased in the conversational situation compared with the baseline (alone) situation, and decreased in the final baseline (alone) situation compared with the conversational situation.

  4. Methylobacteria isolated from bryophytes and the 2-fold description of the same microbial species.

    PubMed

    Schauer, S; Kutschera, U

    2013-02-01

    On the surface of healthy land plants (embryophytes), numerous non-pathogenic bacteria have been discovered and described. Among these epiphytic microbes, pink-pigmented facultative methylotrophic microbes of the genus Methylobacterium are of special significance, because these microorganisms consume methanol emitted via the stomatal pores and secrete growth-promoting phytohormones. Methylobacterium funariae, Schauer and Kutschera 2011, a species isolated in our lab from the common cord moss, described as a nova species in this journal, was recently characterized for a second time as a "new taxon" under a different name, "M. bullatum." Based on a phylogenetic analysis, we show that these taxa are identical. In addition, we provide novel information on the exact cell size, and describe the correct type locality of this bacterial species, which was classified as a phytosymbiont. Finally, we discuss the hypothesis that certain methylobacteria may preferentially colonize bryophytes. With reference to our recent discovery that thalli of ferns form, like liverworts and moss protonemata, associations with methylobacteria, we argue that the haploid phase of cryptogames are preferred host organisms of these pink-pigmented microbial phytosymbionts.

  5. PACE Force Field for Protein Simulations. 2. Folding Simulations of Peptides.

    PubMed

    Han, Wei; Wan, Cheuk-Kin; Wu, Yun-Dong

    2010-11-01

    We present the application of our recently developed PACE force field to the folding of peptides. These peptides include α-helical (AK17 and Fs), β-sheet (GB1m2 and Trpzip2), and mixed helical/coil (Trp-cage) peptides. With replica exchange molecular dynamics (REMD), our force field can fold the five peptides into their native structures while maintaining their stabilities reasonably well. Our force field is also able to capture important thermodynamic features of the five peptides that have been observed in previous experimental and computational studies, such as different preferences for a helix-turn-helix topology for AK17 and Fs, the relative contribution of four hydrophobic side chains of GB1p to the stability of β-hairpin, and the distinct role of a hydrogen bond involving Trp-Hε and a D9/R16 salt bridge in stabilizing the Trp-cage native structure. Furthermore, multiple folding and unfolding events are observed in our microsecond-long normal MD simulations of AK17, Trpzip2, and Trp-cage. These simulations provide mechanistic information such as a "zip-out" pathway of the folding mechanism of Trpzip2 and the folding times of AK17 and Trp-cage, which are estimated to be about 51 ± 43 ns and 270 ± 110 ns, respectively. A 600 ns simulation of the peptides can be completed within one day. These features of our force field are potentially applicable to the study of thermodynamics and kinetics of real protein systems.

  6. Phase comparator apparatus and method

    DOEpatents

    Coffield, Frederick E.

    1987-01-01

    The phase change to be measured is multiply measured at artificially incred and decreased values and then averaged to result in greater accuracy. Delayed versions of the reference and input signals are compared in dual channels to the undelayed input signal and the undelayed reference signal, respectively. Resulting time-lengthened and time-shortened phase measurement signals from the dual comparator channels are algebraically combined to provide an analog output signal having an average magnitude accurately proportional to the true phase difference between the undelayed reference and the undelayed input signals. Increased linearity/reproducibility results where relatively high frequency signals (e.g., up to 70 MHz or more) are to be phase compared. An optional voltage clamp on the comparator channel outputs further improves linearity/reproducibility where very small phase differences are being measured.

  7. Experiencing discrimination increases risk taking.

    PubMed

    Jamieson, Jeremy P; Koslov, Katrina; Nock, Matthew K; Mendes, Wendy Berry

    2013-02-01

    Prior research has revealed racial disparities in health outcomes and health-compromising behaviors, such as smoking and drug abuse. It has been suggested that discrimination contributes to such disparities, but the mechanisms through which this might occur are not well understood. In the research reported here, we examined whether the experience of discrimination affects acute physiological stress responses and increases risk-taking behavior. Black and White participants each received rejecting feedback from partners who were either of their own race (in-group rejection) or of a different race (out-group rejection, which could be interpreted as discrimination). Physiological (cardiovascular and neuroendocrine) changes, cognition (memory and attentional bias), affect, and risk-taking behavior were assessed. Significant participant race × partner race interactions were observed. Cross-race rejection, compared with same-race rejection, was associated with lower levels of cortisol, increased cardiac output, decreased vascular resistance, greater anger, increased attentional bias, and more risk-taking behavior. These data suggest that perceived discrimination is associated with distinct profiles of physiological reactivity, affect, cognitive processing, and risk taking, implicating direct and indirect pathways to health disparities.

  8. Lactic acid fermentation stimulated iron absorption by Caco-2 cells is associated with increased soluble iron content in carrot juice.

    PubMed

    Bergqvist, Sharon W; Andlid, Thomas; Sandberg, Ann-Sofie

    2006-10-01

    An in vitro digestion/Caco-2 cell model was applied to explore the impact of lactic acid (LA) fermentation by Lactobacillus pentosus FSC1 and Leuconostoc mesenteroides FSC2 on the Fe bioavailability of carrot juice. The redox state of Fe in fermented carrot juice was also assessed as a crucial factor for absorption. LA fermentation was shown to improve mineral solubility to different extents at simulated physiological conditions: Mn (2-fold); Fe (1.5-1.7-fold); Zn (1.2-fold); Cu (1-fold). Soluble Fe2+ was increased about 16-fold by LA fermentation, and about one third of the Fe2+ remained soluble after in vitro digestion (about 4-5-fold higher than in fresh juice). Data on cell-line studies showed a 4-fold increase in the efficiency of Fe uptake, but not in transepithelial transfer by Caco2 cells, as a result of fermentation. The increases in Fe2+ level and the efficiency of cellular Fe uptake were strain-dependent. To sum up the effect on both Fe solubility and cellular uptake efficiency, the amount of cellularly absorbed Fe from Ln. mesenteroides FSC2-fermented juice was about 20 % higher than that from L. pentosus FSC1-fermented juice (22.7 v. 19.2 microg/l juice per mg protein). To conclude, LA fermentation enhanced Fe absorption by Caco-2 cells from carrot juice because of increases in not only Fe solubility after digestion, but also the efficiency of cellular Fe uptake. The fermentation-improved efficiency of Fe uptake was possibly due to the increased level of soluble Fe2+ rather than a being a strain-specific event.

  9. NSF and NASA budgets increased

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    Research budgets of several of the federal government agencies were increased significantly over the Reagan administration's requests in the House of Representative's appropriations bill H.R. 4034. These budgets had been removed from the Reagan administration's omnibus reconciliation bill, and thus there were worries expressed that certain research funding could be in jeopardy. The rationale was that because the requests were voted on individually on the floor of the House, many sections of the budgets would be subjected to extra scrutiny, which would lead to more cuts.The National Science Foundation (NSF) budget request had been cut and reordered by the Office of Management and Budget (OMB) by making sharp reductions in programs of the social sciences and in programs of science and engineering education. There were fears that these programs would be reinstated to the original request level, at the expense of the budgets of other research activities. These fears materialized, but only momentarily. Efforts to cut the research activities by the House Appropriations Committee were soundly defeated. The budget was supported, with additional increases to provide for the education programs, by a high margin, which included most Republican and Democratic members of the House of Representatives. The overall NSF budget, as passed, has a total appropriation of $1103.5 million, compared with the Administration's request of $1033.5 million (the Fiscal Year 1981 appropriation for the NSF was $1022.4 million). The House approved budget included increases of $44.9 million in research and $25.1 million in science and engineering education. Included in the research budget increase were recommendations by the House Appropriations Committee for support of the social sciences and for the international affairs programs. Also included in the recommendations was support of interdisciplinary research programs that cut across the directorates of the NSF.

  10. Increased fructose 1,6-bisphosphate aldolase in plastids enhances growth and photosynthesis of tobacco plants.

    PubMed

    Uematsu, Kimio; Suzuki, Nobuaki; Iwamae, Tomoko; Inui, Masayuki; Yukawa, Hideaki

    2012-05-01

    The Calvin cycle is the initial pathway of photosynthetic carbon fixation, and several of its reaction steps are suggested to exert rate-limiting influence on the growth of higher plants. Plastid fructose 1,6-bisphosphate aldolase (aldolase, EC 4.1.2.13) is one of the nonregulated enzymes comprising the Calvin cycle and is predicted to have the potential to control photosynthetic carbon flux through the cycle. In order to investigate the effect of overexpression of aldolase, this study generated transgenic tobacco (Nicotiana tabacum L. cv Xanthi) expressing Arabidopsis plastid aldolase. Resultant transgenic plants with 1.4-1.9-fold higher aldolase activities than those of wild-type plants showed enhanced growth, culminating in increased biomass, particularly under high CO₂ concentration (700 ppm) where the increase reached 2.2-fold relative to wild-type plants. This increase was associated with a 1.5-fold elevation of photosynthetic CO₂ fixation in the transgenic plants. The increased plastid aldolase resulted in a decrease in 3-phosphoglycerate and an increase in ribulose 1,5-bisphosphate and its immediate precursors in the Calvin cycle, but no significant changes in the activities of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) or other major enzymes of carbon assimilation. Taken together, these results suggest that aldolase overexpression stimulates ribulose 1,5-bisphosphate regeneration and promotes CO₂ fixation. It was concluded that increased photosynthetic rate was responsible for enhanced growth and biomass yields of aldolase-overexpressing plants.

  11. [Experimental study on the possibility of using live tularemia vaccine to increase resistance to heterologous infection disease].

    PubMed

    Iliukhin, V I; Plekhanova, N G; Senina, T V; Stanovaia, O V; Kislichkin, N N

    2004-01-01

    In experiments on guinea pigs immunized with Francisella tularensis 15, or live tularemia vaccine (LTV), the level of heterologous protective effect to dangerous infectious diseases caused by Yersinia pestis, Burkholderia pseudomallei, B. mallei, Mycobacterium tuberculosis was studied. The study revealed that during the first 4 weeks after the subcutaneous immunization with LTV the level of resistance of the immunized animals to heterologous infective agent reliably increased as indicated by the survival rate of the animals, as well as by the survival time of those killed by infection, in comparison with the controls. Later (on day 150 after immunization) differences in death rate between the groups perceptibly decreased. Nevertheless, the 1 1/2-fold increase of the survival time of the challenged immunized animals in comparison with the controls proved the possibility of using immunization with LTV for the urgent prophylaxis and treatment not only of tularemia, but also of plague, glanders, melioidosis and tuberculosis.

  12. Differential comparator cirucit

    DOEpatents

    Hickling, Ronald M.

    1996-01-01

    A differential comparator circuit for an Analog-to-Digital Converter (ADC) or other application includes a plurality of differential comparators and a plurality of offset voltage generators. Each comparator includes first and second differentially connected transistor pairs having equal and opposite voltage offsets. First and second offset control transistors are connected in series with the transistor pairs respectively. The offset voltage generators generate offset voltages corresponding to reference voltages which are compared with a differential input voltage by the comparators. Each offset voltage is applied to the offset control transistors of at least one comparator to set the overall voltage offset of the comparator to a value corresponding to the respective reference voltage. The number of offset voltage generators required in an ADC application can be reduced by a factor of approximately two by applying the offset voltage from each offset voltage generator to two comparators with opposite logical sense such that positive and negative offset voltages are produced by each offset voltage generator.

  13. Text File Comparator

    NASA Technical Reports Server (NTRS)

    Kotler, R. S.

    1983-01-01

    File Comparator program IFCOMP, is text file comparator for IBM OS/VScompatable systems. IFCOMP accepts as input two text files and produces listing of differences in pseudo-update form. IFCOMP is very useful in monitoring changes made to software at the source code level.

  14. Comparing Adult Education Worldwide.

    ERIC Educational Resources Information Center

    Charters, Alexander N.; And Others

    Comparative international adult education, defined as that field in which adult educators from various countries compare their own institutions and practices with those of their counterparts in other nations, is examined. Provided is an account of adult education in nine European socialist countries (including the Soviet Union), as well as…

  15. Studies on water transport through the sweet cherry fruit surface: IX. Comparing permeability in water uptake and transpiration.

    PubMed

    Beyer, Marco; Lau, Steffen; Knoche, Moritz

    2005-01-01

    Water uptake and transpiration were studied through the surface of intact sweet cherry (Prunus avium L.) fruit, exocarp segments (ES) and cuticular membranes (CM) excised from the cheek of sweet cherry fruit and astomatous CM isolated from Schefflera arboricola (Hayata) Hayata, Citrus aurantium L., and Stephanotis floribunda Brongn. leaves or from Lycopersicon esculentum Mill. and Capsicum annuum L. var. annuum Fasciculatum Group fruit. ES and CM were mounted in diffusion cells. Water (deionized) uptake into intact sweet cherry fruit, through ES or CM interfacing water as a donor and a polyethyleneglycol (PEG 6000, osmotic pressure 2.83 MPa)-containing receiver was determined gravimetrically. Transpiration was quantified by monitoring weight loss of a PEG 6000-containing donor (2.83 MPa) against dry silica as a receiver. The permeability coefficients for osmotic water uptake and transpiration were calculated from the amount of water taken up or transpired per unit surface area and time, and the driving force for transport. Permeability during osmotic water uptake was markedly higher than during transpiration in intact sweet cherry fruit (40.2-fold), excised ES of sweet cherry fruit (12.5- to 53.7-fold) and isolated astomatous fruit and leaf CM of a range of species (on average 23.0-fold). Partitioning water transport into stomatal and cuticular components revealed that permeability of the sweet cherry fruit cuticle for water uptake was 11.9-fold higher and that of stomata 56.8-fold higher than the respective permeability during transpiration. Increasing water vapor activity in the receiver from 0 to 1 increased permeability during transpiration across isolated sweet cherry fruit CM about 2.1-fold. Permeability for vapor uptake from saturated water vapor into a PEG 6000 receiver solution was markedly lower than from liquid water, but of similar magnitude to the permeability during self-diffusion of (3)H(2)O in the absence of osmotica. The energy of activation for

  16. Studies on water transport through the sweet cherry fruit surface: IX. Comparing permeability in water uptake and transpiration.

    PubMed

    Beyer, Marco; Lau, Steffen; Knoche, Moritz

    2005-01-01

    Water uptake and transpiration were studied through the surface of intact sweet cherry (Prunus avium L.) fruit, exocarp segments (ES) and cuticular membranes (CM) excised from the cheek of sweet cherry fruit and astomatous CM isolated from Schefflera arboricola (Hayata) Hayata, Citrus aurantium L., and Stephanotis floribunda Brongn. leaves or from Lycopersicon esculentum Mill. and Capsicum annuum L. var. annuum Fasciculatum Group fruit. ES and CM were mounted in diffusion cells. Water (deionized) uptake into intact sweet cherry fruit, through ES or CM interfacing water as a donor and a polyethyleneglycol (PEG 6000, osmotic pressure 2.83 MPa)-containing receiver was determined gravimetrically. Transpiration was quantified by monitoring weight loss of a PEG 6000-containing donor (2.83 MPa) against dry silica as a receiver. The permeability coefficients for osmotic water uptake and transpiration were calculated from the amount of water taken up or transpired per unit surface area and time, and the driving force for transport. Permeability during osmotic water uptake was markedly higher than during transpiration in intact sweet cherry fruit (40.2-fold), excised ES of sweet cherry fruit (12.5- to 53.7-fold) and isolated astomatous fruit and leaf CM of a range of species (on average 23.0-fold). Partitioning water transport into stomatal and cuticular components revealed that permeability of the sweet cherry fruit cuticle for water uptake was 11.9-fold higher and that of stomata 56.8-fold higher than the respective permeability during transpiration. Increasing water vapor activity in the receiver from 0 to 1 increased permeability during transpiration across isolated sweet cherry fruit CM about 2.1-fold. Permeability for vapor uptake from saturated water vapor into a PEG 6000 receiver solution was markedly lower than from liquid water, but of similar magnitude to the permeability during self-diffusion of (3)H(2)O in the absence of osmotica. The energy of activation for

  17. Sugar transport regulation: comparative characterization of the effect of NADH CoQ reductase deficiency in two cell culture systems.

    PubMed

    Germinario, R J; Continelli, L; Pratt, S

    2000-11-01

    In this report, we have characterized the upregulation of glucose transport in two different respiration-deficient fibroblast cell cultures. We have demonstrated that glucose transport increases in respiration-deficient cells as measured by 2 deoxy D-glucose transport and is readily observed in both the WG750 human and G14 Chinese hamster fibroblast respiration-deficient cell lines when compared with the MCH55 normal human and V79 parental Chinese hamster cell lines, respectively. Using subcellular fractionation techniques, the GLUT 1 glucose transporter was found located predominantly in the plasma membrane-enriched fraction of the human and hamster cell lines. In human cells, the expression of the GLUT 1 glucose transporter was elevated three-fold in the plasma membrane-enriched fraction of the WG750 respiration-deficient mutant cells. In the Chinese hamster cell lines, the respiration-deficient G14 cells exhibited no such GLUT 1 glucose transporter elevation in the plasma membrane-enriched fraction, yet expressed a >2-fold increase in glucose transport. Furthermore, the G14 cells had a similar content of GLUT 1 glucose transporter in the plasma membrane fraction when compared with the V79 parental cell line. Using Western blot analysis, the GLUT 1 glucose transporter in G14 cells exhibited a different mobility on a polyacrylamide gel when compared with the mobility of the GLUT 1 glucose transporter of the V79 cell line. This differential mobility of the glucose transporters in the hamster cells appeared to be related to glycosylation differences of the glucose transporters. Although normal human and hamster cell lines exhibited significant increases in insulin-stimulated sugar transport (P < 0.05), the two respective respiration-deficient cell lines exhibited no significant increases in insulin-stimulated sugar transport (P > 0.05). Additionally, the expression of the GLUT 1 mRNA in the human WG750 mutant cells was elevated when compared with GLUT 1 mRNA in

  18. Hybridization increases invasive knotweed success

    PubMed Central

    Parepa, Madalin; Fischer, Markus; Krebs, Christine; Bossdorf, Oliver

    2014-01-01

    Hybridization is one of the fundamental mechanisms by which rapid evolution can occur in exotic species. If hybrids show increased vigour, this could significantly contribute to invasion success. Here, we compared the success of the two invasive knotweeds, Fallopia japonica and F. sachalinensis, and their hybrid, F. × bohemica, in competing against experimental communities of native plants. Using plant material from multiple clones of each taxon collected across a latitudinal gradient in Central Europe, we found that knotweed hybrids performed significantly better in competition with a native community and that they more strongly reduced the growth of the native plants. One of the parental species, F. sachalinensis, regenerated significantly less well from rhizomes, and this difference disappeared if activated carbon was added to the substrate, which suggests allelopathic inhibition of F. sachalinensis regeneration by native plants. We found substantial within-taxon variation in competitive success in all knotweed taxa, but variation was generally greatest in the hybrid. Interestingly, there was also significant variation within the genetically uniform F. japonica, possibly reflecting epigenetic differences. Our study shows that invasive knotweed hybrids are indeed more competitive than their parents and that hybridization increased the invasiveness of the exotic knotweed complex. PMID:24665343

  19. Hybridization increases invasive knotweed success.

    PubMed

    Parepa, Madalin; Fischer, Markus; Krebs, Christine; Bossdorf, Oliver

    2014-03-01

    Hybridization is one of the fundamental mechanisms by which rapid evolution can occur in exotic species. If hybrids show increased vigour, this could significantly contribute to invasion success. Here, we compared the success of the two invasive knotweeds, Fallopia japonica and F. sachalinensis, and their hybrid, F. × bohemica, in competing against experimental communities of native plants. Using plant material from multiple clones of each taxon collected across a latitudinal gradient in Central Europe, we found that knotweed hybrids performed significantly better in competition with a native community and that they more strongly reduced the growth of the native plants. One of the parental species, F. sachalinensis, regenerated significantly less well from rhizomes, and this difference disappeared if activated carbon was added to the substrate, which suggests allelopathic inhibition of F. sachalinensis regeneration by native plants. We found substantial within-taxon variation in competitive success in all knotweed taxa, but variation was generally greatest in the hybrid. Interestingly, there was also significant variation within the genetically uniform F. japonica, possibly reflecting epigenetic differences. Our study shows that invasive knotweed hybrids are indeed more competitive than their parents and that hybridization increased the invasiveness of the exotic knotweed complex. PMID:24665343

  20. p38 Mitogen-Activated Protein Kinase (MAPK) Increases Arginase Activity and Contributes to Endothelial Dysfunction in Corpora Cavernosa from Angiotensin-II Treated Mice

    PubMed Central

    Toque, Haroldo A.; Romero, Maritza J.; Tostes, Rita C.; Shatanawi, Alia; Chandra, Surabhi; Carneiro, Zidonia N.; Inscho, Edward W.; Webb, R. Clinton; Caldwell, Ruth B.; Caldwell, R. William

    2010-01-01

    Introduction Angiotensin II (AngII) activates p38 mitogen-activated protein kinase (MAPK) and elevates arginase activity in endothelial cells. Upregulation of arginase activity has been implicated in endothelial dysfunction by reducing NO bioavailability. However, signaling pathways activated by AngII in the penis are largely unknown. Aim We hypothesized that activation of p38 MAPK increases arginase activity and thus impairs penile vascular function in AngII-treated mice. Methods Male C57BL/6 mice were implanted with osmotic minipumps containing saline or AngII (42 μg/kg/h) for 14 days and co-treated with p38 MAPK inhibitor, SB 203580 (5 μg/kg/day), beginning 2 days before minipump implantation. Systolic blood pressure (SBP) was measured. Corpus cavernosum (CC) tissue was used for vascular functional studies and protein expression levels of p38 MAPK, arginase and constitutive NOS, and arginase activity. Main Outcome Measures Arginase expression and activity; expression of phospho-p38 MAPK, -eNOS and nNOS proteins; endothelium-dependent and nitrergic nerve-mediated relaxations were determined in CC from control and AngII-infused mice. Results AngII increased SBP (22%) and increased CC arginase activity and expression (~2-fold), and phosphorylated P38 MAPK levels (30%) over control. Treatment with SB 203580 prevented these effects. Endothelium-dependent NO-mediated relaxation to acetylcholine was significantly reduced by AngII and this effect was prevented by SB 203580 (P<0.01). AngII (2-week) did not alter nitrergic function. However, SB 203580 significantly increased nitrergic relaxation in both control and AngII tissue at lower frequencies. Maximum contractile responses for phenylephrine and electrical field stimulation were increased by AngII (56% and 171%, respectively), and attenuated by SB 203580 treated. AngII treatment also decreased eNOS phosphorylation at Ser-1177 compared to control. Treatment with SB 203580 prevented all these changes. Conclusion p38

  1. Postcolonialism And Comparative Education

    NASA Astrophysics Data System (ADS)

    Tikly, Leon

    1999-11-01

    The article considers the relevance of recent developments in postcolonial theory for comparative education research. The article starts with an account of these developments. This account is then used as a basis for a critical discussion of previous theoretical frameworks that have been used by comparative researchers to explain the colonial legacy. The implications of adopting a postcolonial approach in comparative education are discussed in relation to issues of race, culture, language and the curriculum. The article concludes by arguing that a consideration of the postcolonial condition is necessary for developing a more holistic and less eurocentric understanding of the relationship between globalisation and education.

  2. Metabolic engineering of lipid catabolism increases microalgal lipid accumulation without compromising growth

    PubMed Central

    Trentacoste, Emily M.; Shrestha, Roshan P.; Smith, Sarah R.; Glé, Corine; Hartmann, Aaron C.; Hildebrand, Mark; Gerwick, William H.

    2013-01-01

    Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of advancing economic feasibility. We report that the targeted knockdown of a multifunctional lipase/phospholipase/acyltransferase increased lipid yields without affecting growth in the diatom Thalassiosira pseudonana. Antisense-expressing knockdown strains 1A6 and 1B1 exhibited wild-type–like growth and increased lipid content under both continuous light and alternating light/dark conditions. Strains 1A6 and 1B1, respectively, contained 2.4- and 3.3-fold higher lipid content than wild-type during exponential growth, and 4.1- and 3.2-fold higher lipid content than wild-type after 40 h of silicon starvation. Analyses of fatty acids, lipid classes, and membrane stability in the transgenic strains suggest a role for this enzyme in membrane lipid turnover and lipid homeostasis. These results demonstrate that targeted metabolic manipulations can be used to increase lipid accumulation in eukaryotic microalgae without compromising growth. PMID:24248374

  3. Comparative Packaging Study

    NASA Technical Reports Server (NTRS)

    Perchonok, Michele; Antonini, David

    2008-01-01

    This viewgraph presentation describes a comparative packaging study for use on long duration space missions. The topics include: 1) Purpose; 2) Deliverables; 3) Food Sample Selection; 4) Experimental Design Matrix; 5) Permeation Rate Comparison; and 6) Packaging Material Information.

  4. Comparative Card Production Methods

    ERIC Educational Resources Information Center

    Turner, Ann Craig

    1972-01-01

    Seven methods of card production tried by the University of British Columbia library are described and compared in terms of total cost per set of cards and their applicability to libraries of various sizes. (5 references) (Author)

  5. Document Update and Compare

    NASA Technical Reports Server (NTRS)

    Knoch, C. F.; Caldwell, D. C.; Caldwell, D. L.

    1983-01-01

    Document Update and Compare programs provide simple computerized documentmaintenance system on Data General NOVA 840 computer. Document Update program allows user to update document either by batch or terminal input. Documents are modified and lists of modifications printed out.

  6. Mechanical code comparator

    DOEpatents

    Peter, Frank J.; Dalton, Larry J.; Plummer, David W.

    2002-01-01

    A new class of mechanical code comparators is described which have broad potential for application in safety, surety, and security applications. These devices can be implemented as micro-scale electromechanical systems that isolate a secure or otherwise controlled device until an access code is entered. This access code is converted into a series of mechanical inputs to the mechanical code comparator, which compares the access code to a pre-input combination, entered previously into the mechanical code comparator by an operator at the system security control point. These devices provide extremely high levels of robust security. Being totally mechanical in operation, an access control system properly based on such devices cannot be circumvented by software attack alone.

  7. Intravenous AAV8 Encoding Urocortin-2 Increases Function of the Failing Heart in Mice

    PubMed Central

    Lai, N. Chin; Gao, Mei Hua; Giamouridis, Dimosthenis; Suarez, Jorge; Miyanohara, Atsushi; Parikh, Jay; Hightower, Stephen; Guo, Tracy; Dillmann, Wolfgang; Kim, Young-Chul; Diaz-Juarez, Julieta

    2015-01-01

    Abstract Urocortin-2 (UCn2) peptide infusion increases cardiac function in patients with heart failure, but chronic peptide infusion is cumbersome, is costly, and provides only short-term benefits. Gene transfer would circumvent these shortcomings. We previously showed that a single intravenous (IV) injection of AAV8.UCn2 increases plasma UCn2 and left ventricular (LV) systolic and diastolic function for at least 7 months in normal mice. Here we test the hypothesis that IV delivery of AAV8.UCn2 increases function of the failing heart. Myocardial infarction (MI, by coronary ligation) was used to induce heart failure, which was assessed by echocardiography 3 weeks after MI. Mice with LV ejection fraction (EF) <25% received IV delivery of AAV8.UCn2 (5×1011 gc) or saline, and 5 weeks later echocardiography showed increased LV EF in mice that received UCn2 gene transfer (p=0.01). In vivo physiological studies showed a 2-fold increase in peak rate of LV pressure development (LV +dP/dt; p<0.0001) and a 1.6-fold increase in peak rate of LV pressure decay (LV −dP/dt; p=0.0007), indicating increased LV systolic and diastolic function in treated mice. UCn2 gene transfer was associated with increased peak systolic Ca2+ transient amplitude and rate of Ca2+ decline and increased SERCA2a expression. In addition, UCn2 gene transfer reduced Thr286 phosphorylation of Cam kinase II, and increased expression of cardiac myosin light chain kinase, findings that would be anticipated to increase function of the failing heart. We conclude that a single IV injection of AAV8.UCn2 increases function of the failing heart. The simplicity of IV injection of a vector encoding a gene with beneficial paracrine effects to increase cardiac function is an attractive potential clinical strategy. PMID:25760560

  8. Bioavailability of beta-carotene (betaC) from purple carrots is the same as typical orange carrots while high-betaC carrots increase betaC stores in Mongolian gerbils (Meriones unguiculatus).

    PubMed

    Dosti, Mandy Porter; Mills, Jordan P; Simon, Philipp W; Tanumihardjo, Sherry A

    2006-08-01

    Vitamin A (VA) deficiency is a worldwide public health problem. Biofortifying existing sources of beta-carotene (betaC) and increasing dietary betaC could help combat the issue. Two studies were performed to investigate the relative betaC bioavailability of a betaC supplement to purple, high-betaC orange, and typical orange carrots using Mongolian gerbils (Meriones unguiculatus). In study 1, which used a traditional bioavailability design, gerbils (n 32) received a diet containing orange, purple, or white carrot powder, or white carrot powder +a betaC supplement. In study 2, which included betaC-biofortified carrots, gerbils (n 39) received orange, high-betaC orange, purple, or white carrot powder in their diet. Both studies lasted 21 d and the gerbils were killed to determine the effect of carrot type or supplement on serum and liver betaC, alpha-carotene, and VA concentrations. Liver stores of betaC or VA in the gerbils did not differ between orange and purple carrot diets when equal amounts of betaC from each of the diets were consumed (P>0.05). Both the orange and purple carrot diet resulted in higher liver VA compared with the supplement (P<0.05). High-betaC carrots resulted in more than 2-fold higher betaC and 1.1 times greater VA liver stores compared with typical orange carrots (P<0.05). These results suggest that high-betaC carrots may be an alternative source of VA to typical carrots in areas of VA deficiency. Second, phenolics including anthocyanins and phenolic acids in purple carrot do not interfere with the bioavailability of betaC from purple carrots.

  9. Sociological analysis and comparative education

    NASA Astrophysics Data System (ADS)

    Woock, Roger R.

    1981-12-01

    It is argued that comparative education is essentially a derivative field of study, in that it borrows theories and methods from academic disciplines. After a brief humanistic phase, in which history and philosophy were central for comparative education, sociology became an important source. In the mid-50's and 60's, sociology in the United States was characterised by Structural Functionalism as a theory, and Social Survey as a dominant methodology. Both were incorporated into the development of comparative education. Increasingly in the 70's, and certainly today, the new developments in sociology are characterised by an attack on Positivism, which is seen as the philosophical position underlying both functionalism and survey methods. New or re-discovered theories with their attendant methodologies included Marxism, Phenomenological Sociology, Critical Theory, and Historical Social Science. The current relationship between comparative education and social science is one of uncertainty, but since social science is seen to be returning to its European roots, the hope is held out for the development of an integrated social theory and method which will provide a much stronger basis for developments in comparative education.

  10. Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

    SciTech Connect

    Trifilieff, Alexandre; Ethell, Brian T.; Sykes, David A.; Watson, Kenny J.; Collingwood, Steve; Charlton, Steven J.; Kent, Toby C.

    2015-08-15

    Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M

  11. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.

    PubMed

    Forstpointner, Roswitha; Dreyling, Martin; Repp, Roland; Hermann, Sandra; Hänel, Annette; Metzner, Bernd; Pott, Christiane; Hartmann, Frank; Rothmann, Frank; Rohrberg, Robert; Böck, Hans-Peter; Wandt, Hannes; Unterhalt, Michael; Hiddemann, Wolfgang

    2004-11-15

    In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.

  12. Virtual Optical Comparator

    SciTech Connect

    Thompson, Greg

    2008-10-20

    The Virtual Optical Comparator, VOC, was conceived as a result of the limitations of conventional optical comparators and vision systems. Piece part designs for mechanisms have started to include precision features on the face of parts that must be viewed using a reflected image rather than a profile shadow. The VOC concept uses a computer generated overlay and a digital camera to measure features on a video screen. The advantage of this system is superior edge detection compared to traditional systems. No vinyl charts are procured or inspected. The part size and expensive fixtures are no longer a concern because of the range of the X-Y table of the Virtual Optical Comparator. Product redesigns require only changes to the CAD image overlays; new vinyl charts are not required. The inspection process is more ergonomic by allowing the operator to view the part sitting at a desk rather than standing over a 30 inch screen. The procurement cost for the VOC will be less than a traditional comparator with a much smaller footprint with less maintenance and energy requirements.

  13. Ensembl comparative genomics resources

    PubMed Central

    Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J.; Searle, Stephen M. J.; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

    2016-01-01

    Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. PMID:26896847

  14. Ensembl comparative genomics resources.

    PubMed

    Herrero, Javier; Muffato, Matthieu; Beal, Kathryn; Fitzgerald, Stephen; Gordon, Leo; Pignatelli, Miguel; Vilella, Albert J; Searle, Stephen M J; Amode, Ridwan; Brent, Simon; Spooner, William; Kulesha, Eugene; Yates, Andrew; Flicek, Paul

    2016-01-01

    Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org.

  15. Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cells

    NASA Technical Reports Server (NTRS)

    Nguyen, K. T.; Frye, S. R.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

    2001-01-01

    Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.

  16. Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57-KIR-NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57-KIR-NKG2A- NK Cells.

    PubMed

    Forslund, Elin; Sohlberg, Ebba; Enqvist, Monika; Olofsson, Per E; Malmberg, Karl-Johan; Önfelt, Björn

    2015-10-01

    NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(-) (lacking inhibitory receptors; IR(-)) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A(+) NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR(-) NK cells. NKG2A(+) NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A(+) NK cells. Conjugates involving IR(-) NK cells were generally more short-lived and IR(-) NK cells did not become activated to the same extent as NKG2A(+) NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A(+) and IR(-) NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A(+) NK cells is linked to processes regulating events in the recognition phase of NK-target cell contact rather than events after cytotoxicity has been triggered. PMID:26320254

  17. Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57-KIR-NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57-KIR-NKG2A- NK Cells.

    PubMed

    Forslund, Elin; Sohlberg, Ebba; Enqvist, Monika; Olofsson, Per E; Malmberg, Karl-Johan; Önfelt, Björn

    2015-10-01

    NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(-) (lacking inhibitory receptors; IR(-)) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A(+) NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR(-) NK cells. NKG2A(+) NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A(+) NK cells. Conjugates involving IR(-) NK cells were generally more short-lived and IR(-) NK cells did not become activated to the same extent as NKG2A(+) NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A(+) and IR(-) NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A(+) NK cells is linked to processes regulating events in the recognition phase of NK-target cell contact rather than events after cytotoxicity has been triggered.

  18. Analysis of Genes for Succinoyl Trehalose Lipid Production and Increasing Production in Rhodococcus sp. Strain SD-74

    PubMed Central

    Inaba, Tomohiro; Tokumoto, Yuta; Miyazaki, Yusuke; Inoue, Naoyuki; Maseda, Hideaki; Nakajima-Kambe, Toshiaki; Uchiyama, Hiroo

    2013-01-01

    Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants produced from n-alkanes that are secreted by Rhodococcus species bacteria. These compounds not only exhibit unique interfacial properties but also demonstrate versatile biochemical actions. In this study, three novel types of genes involved in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA) transferase (tlsA), fructose-bisphosphate aldolase (fda), and alkane monooxygenase (alkB), were identified. The predicted functions of these genes indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups are important for the biosynthesis of STLs. Based on these results, we propose a biosynthesis pathway for STLs from alkanes in Rhodococcus sp. strain SD-74. By overexpressing tlsA, we achieved a 2-fold increase in the production of STLs. This study advances our understanding of bacterial glycolipid production in Rhodococcus species. PMID:24038682

  19. Comparative Higher Education.

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    The comparative higher education course offered at the State University of New York at Buffalo is briefly described, and a course schedule is presented, including required and recommended readings for each topic. The course is intended to provide a broad cross-cultural perspective and considers the growth and development of universities in Europe,…

  20. Comparative Cognitive Development

    ERIC Educational Resources Information Center

    Matsuzawa, Tetsuro

    2007-01-01

    This paper aims to compare cognitive development in humans and chimpanzees to illuminate the evolutionary origins of human cognition. Comparison of morphological data and life history strongly highlights the common features of all primate species, including humans. The human mother-infant relationship is characterized by the physical separation of…

  1. Trends in Comparative Education.

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    1991-01-01

    Examines societal and academic factors influencing the development of comparative education since 1945, particularly in the United States. Discusses the dominance of structural functionalism and human capital theory in the 1960s, the recent shift to diverse research orientations and ideologies, and effects of institutional decline and…

  2. Terrestrial Planets: Comparative Planetology

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Papers were presented at the 47th Annual Meteoritical Society Meeting on the Comparative planetology of Terrestrial Planets. Subject matter explored concerning terrestrial planets includes: interrelationships among planets; plaentary evolution; planetary structure; planetary composition; planetary Atmospheres; noble gases in meteorites; and planetary magnetic fields.

  3. Comparing Item Characteristic Curves.

    ERIC Educational Resources Information Center

    Rosenbaum, Paul R.

    1987-01-01

    This paper develops and applies three nonparametric comparisons of the shapes of two item characteristic surfaces: (1) proportional latent odds; (2) uniform relative difficulty; and (3) item sensitivity. A method is presented for comparing the relative shapes of two item characteristic curves in two examinee populations who were administered an…

  4. Comparative Index Terms.

    ERIC Educational Resources Information Center

    Rasheed, Muhammad Abdur

    1989-01-01

    Describes a study that compared indexing terms suggested by authors of articles in "The American Journal of the Medical Science" and indexing terms assigned to the same articles in MEDLARS. Case studies are used to examine the differences between author and indexer indexing. (CLB)

  5. Postcolonialism and Comparative Education.

    ERIC Educational Resources Information Center

    Tikly, Leon

    1999-01-01

    Discusses the implications of adopting a postcolonial approach in comparative education in relation to issues of race, culture, language, and the curriculum. Concludes by arguing that a consideration of the post-colonial condition is necessary for developing a more holistic and less eurocentric understanding of the relationship between…

  6. Comparative cardiac imaging

    SciTech Connect

    Brundage, B.H.

    1990-01-01

    This book is designed to compare all major cardiac imaging techniques. All major imaging techniques - including conventional angiography, digital angiography, echocardiography and Doppler imaging, conventional radioisotope techniques, computed tomography, and magnetic resonance imaging - are covered in this text as they apply to the major cardiovascular disorders. There is brief coverage of positron emission tomography and an extensive presentation of ultrafast computed tomography.

  7. Slow motion increases perceived intent.

    PubMed

    Caruso, Eugene M; Burns, Zachary C; Converse, Benjamin A

    2016-08-16

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor's intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in "slow motion." Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception.

  8. Slow motion increases perceived intent

    PubMed Central

    Caruso, Eugene M.; Burns, Zachary C.; Converse, Benjamin A.

    2016-01-01

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor’s intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in “slow motion.” Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception. PMID:27482091

  9. Slow motion increases perceived intent.

    PubMed

    Caruso, Eugene M; Burns, Zachary C; Converse, Benjamin A

    2016-08-16

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor's intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in "slow motion." Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception. PMID:27482091

  10. Increased chronic acceleration exposure enhances work capacity.

    PubMed

    Burton, R R; Smith, A H

    1997-10-01

    Adult male chickens adapted to 1.75 or 2.5 G from long term centrifugation, were maximally exercised on an animal treadmill at 1 g (Earth's gravity) and compared with the exercise capacities of control chickens raised at 1 g. The increased-G birds had statistically significantly greater exercise capacities than the controls during the first 3 weeks of the study after the initial exercise exposure. Thereafter however for the following two months of the study, there was no difference in either group's exercise capacities. This early increased work capacity was attributed to the increased-G birds improved ability to maximize their muscular strength with neurological adaptation. The increased-G birds lost body mass at a 31% greater rate during exercise than the controls although this difference was not statistically significant. This increased body mass loss was considered to have resulted from increased use of glycogen during exercise.

  11. Enhancer Identification through Comparative Genomics

    SciTech Connect

    Visel, Axel; Bristow, James; Pennacchio, Len A.

    2006-10-01

    With the availability of genomic sequence from numerousvertebrates, a paradigm shift has occurred in the identification ofdistant-acting gene regulatory elements. In contrast to traditionalgene-centric studies in which investigators randomly scanned genomicfragments that flank genes of interest in functional assays, the modernapproach begins electronically with publicly available comparativesequence datasets that provide investigators with prioritized lists ofputative functional sequences based on their evolutionary conservation.However, although a large number of tools and resources are nowavailable, application of comparative genomic approaches remains far fromtrivial. In particular, it requires users to dynamically consider thespecies and methods for comparison depending on the specific biologicalquestion under investigation. While there is currently no single generalrule to this end, it is clear that when applied appropriately,comparative genomic approaches exponentially increase our power ingenerating biological hypotheses for subsequent experimentaltesting.

  12. Internationally Comparable Health Indices

    PubMed Central

    Meijer, Erik; Kapteyn, Arie; Andreyeva, Tatiana

    2013-01-01

    One of the most intractable problems in international health research is the lack of comparability of health measures across countries or cultures. We develop a cross-country measurement model for health in which functional limitations, self-reports of health, and a physical measure are interrelated to construct health indices. To establish comparability across countries, we define the measurement scales by the physical measure while other parameters vary by country to reflect cultural and linguistic differences in response patterns. We find significant cross-country variation in response styles of health reports along with variability in genuine health that is related to differences in national income. Our health indices achieve satisfactory reliability of about 80% and their gradients by age, income, and wealth for the most part show the expected patterns. Moreover, the health indices correlate much more strongly with income and net worth than self reported health measures. PMID:20572201

  13. Banking: shop and compare.

    PubMed

    O'Brien, Jennifer A; DeJarnette, Sherry

    2014-01-01

    There are many reasons to take a critical look at the practice's banking relationship(s)--technology advancements, security measures, improvements in available services, recent banking enhancements designed specifically for medical practices, the impact of the financial crisis on bank ratings and stability, changing practice needs, opportunities for operational automation at the practice--and it is just simply smart to periodically evaluate and compare the features, pricing, and potential savings offered by vendors.

  14. Banking: shop and compare.

    PubMed

    O'Brien, Jennifer A; DeJarnette, Sherry

    2014-01-01

    There are many reasons to take a critical look at the practice's banking relationship(s)--technology advancements, security measures, improvements in available services, recent banking enhancements designed specifically for medical practices, the impact of the financial crisis on bank ratings and stability, changing practice needs, opportunities for operational automation at the practice--and it is just simply smart to periodically evaluate and compare the features, pricing, and potential savings offered by vendors. PMID:25108982

  15. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  16. Teaching about Comparative Government

    ERIC Educational Resources Information Center

    Risinger, C. Frederick

    2009-01-01

    As international relationships become increasingly important (with both friendly and not-so-friendly governments), the author believes that it is important for U.S. students to learn about how a parliamentary democracy works--how it is similar, but different from a presidential-style government. Learning about the systems of government of other…

  17. Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind.

    PubMed

    Hudda, Neelakshi; Gould, Tim; Hartin, Kris; Larson, Timothy V; Fruin, Scott A

    2014-06-17

    We measured the spatial pattern of particle number (PN) concentrations downwind from the Los Angeles International Airport (LAX) with an instrumented vehicle that enabled us to cover larger areas than allowed by traditional stationary measurements. LAX emissions adversely impacted air quality much farther than reported in previous airport studies. We measured at least a 2-fold increase in PN concentrations over unimpacted baseline PN concentrations during most hours of the day in an area of about 60 km(2) that extended to 16 km (10 miles) downwind and a 4- to 5-fold increase to 8-10 km (5-6 miles) downwind. Locations of maximum PN concentrations were aligned to eastern, downwind jet trajectories during prevailing westerly winds and to 8 km downwind concentrations exceeded 75 000 particles/cm(3), more than the average freeway PN concentration in Los Angeles. During infrequent northerly winds, the impact area remained large but shifted to south of the airport. The freeway length that would cause an impact equivalent to that measured in this study (i.e., PN concentration increases weighted by the area impacted) was estimated to be 280-790 km. The total freeway length in Los Angeles is 1500 km. These results suggest that airport emissions are a major source of PN in Los Angeles that are of the same general magnitude as the entire urban freeway network. They also indicate that the air quality impact areas of major airports may have been seriously underestimated. PMID:24871496

  18. Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind.

    PubMed

    Hudda, Neelakshi; Gould, Tim; Hartin, Kris; Larson, Timothy V; Fruin, Scott A

    2014-06-17

    We measured the spatial pattern of particle number (PN) concentrations downwind from the Los Angeles International Airport (LAX) with an instrumented vehicle that enabled us to cover larger areas than allowed by traditional stationary measurements. LAX emissions adversely impacted air quality much farther than reported in previous airport studies. We measured at least a 2-fold increase in PN concentrations over unimpacted baseline PN concentrations during most hours of the day in an area of about 60 km(2) that extended to 16 km (10 miles) downwind and a 4- to 5-fold increase to 8-10 km (5-6 miles) downwind. Locations of maximum PN concentrations were aligned to eastern, downwind jet trajectories during prevailing westerly winds and to 8 km downwind concentrations exceeded 75 000 particles/cm(3), more than the average freeway PN concentration in Los Angeles. During infrequent northerly winds, the impact area remained large but shifted to south of the airport. The freeway length that would cause an impact equivalent to that measured in this study (i.e., PN concentration increases weighted by the area impacted) was estimated to be 280-790 km. The total freeway length in Los Angeles is 1500 km. These results suggest that airport emissions are a major source of PN in Los Angeles that are of the same general magnitude as the entire urban freeway network. They also indicate that the air quality impact areas of major airports may have been seriously underestimated.

  19. Increase in β-ionone, a carotenoid-derived volatile in zeaxanthin-biofortified sweet corn.

    PubMed

    Gallon, Camilla Z; Fuller, Steven C; Fanning, Kent J; Smyth, Heather E; Pun, Sharon; Martin, Ian F; O'Hare, Timothy J

    2013-07-31

    Carotenoids are responsible for the yellow color of sweet corn (Zea mays var. saccharata), but are also potentially the source of flavor compounds from the cleavage of carotenoid molecules. The carotenoid-derived volatile, β-ionone, was identified in both standard yellow sweet corn ('Hybrix5') and a zeaxanthin-enhanced experimental variety ('HZ') designed for sufferers of macular degeneration. As β-ionone is highly perceivable at extremely low concentration by humans, it was important to confirm if alterations in carotenoid profile may also affect flavor volatiles. The concentration of β-ionone was most strongly correlated (R(2) > 0.94) with the β-arm carotenoids, β-carotene, β-cryptoxanthin, and zeaxanthin, and to a lesser degree (R(2) = 0.90) with the α-arm carotenoid, zeinoxanthin. No correlation existed with either lutein (R(2) = 0.06) or antheraxanthin (R(2) = 0.10). Delaying harvest of cobs resulted in a significant increase of both carotenoid and β-ionone concentrations, producing a 6-fold increase of β-ionone in 'HZ' and a 2-fold increase in 'Hybrix5', reaching a maximum of 62 μg/kg FW and 24 μg/kg FW, respectively. PMID:23767984

  20. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus.

    PubMed

    Wolf, Susanne A; Steiner, Barbara; Wengner, Antje; Lipp, Martin; Kammertoens, Thomas; Kempermann, Gerd

    2009-09-01

    To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.

  1. Supplementation of branched-chain amino acids to a reduced-protein diet improves growth performance in piglets: involvement of increased feed intake and direct muscle growth-promoting effect.

    PubMed

    Zheng, Liufeng; Wei, Hongkui; Cheng, Chuanshang; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2016-06-01

    The aim of this study was to investigate whether supplementing branched-chain amino acids (AA) (BCAA) along with a reduced-protein diet increases piglet growth, and whether elevated feed intake and muscle growth-promoting effect contribute to this improvement. In Expt 1, twenty-eight weanling piglets were randomly fed one of the following four diets: a positive control (PC) diet, a reduced-protein negative control (NC) diet, an NC diet supplemented with BCAA to the same levels as in the PC diet (test 1 (T1)) and an NC diet supplemented with a 2-fold dose of BCAA in T1 diet (test 2 (T2)) for 28 d. In Expt 2, twenty-one weanling piglets were randomly assigned to NC, T1 and pair-fed T1 (P) groups. NC and T1 diets were the same as in Expt 1, whereas piglets in the P group were individually pair-fed with the NC group. In Expt 1, the NC group had reduced piglet growth and feed intake compared with the PC group, which were restored in T1 and T2 groups, but no differences were detected between T1 and T2 groups. In Expt 2, T1 and P groups showed increases in growth and mass of some muscles compared with the NC group. Increased feed intake after BCAA supplementation was associated with increased mRNA expressions of agouti-related peptide and co-express neuropeptide Y (NPY) and phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 (S6K1), as well as decreased mRNA expressions of melanocortin-4 receptor and cocaine- and amphetamine-regulated transcript and phosphorylation of eukaryotic initiation factor 2α in the hypothalamus. No differences were observed among PC, T1 and T2 groups except for higher NPY mRNA expression in the T2 group than in the PC group (Expt 1). Phosphorylation of mTOR and S6K1 in muscle was enhanced after BCAA supplementation, which was independent of change in feed intake (Expt 2). In conclusion, supplementing BCAA to reduced-protein diets increases feed intake and muscle mass, and contributes to better growth

  2. Ferroelectric optical image comparator

    DOEpatents

    Butler, Michael A.; Land, Cecil E.; Martin, Stephen J.; Pfeifer, Kent B.

    1993-01-01

    A ferroelectric optical image comparator has a lead lanthanum zirconate titanate thin-film device which is constructed with a semi-transparent or transparent conductive first electrode on one side of the thin film, a conductive metal second electrode on the other side of the thin film, and the second electrode is in contact with a nonconducting substrate. A photoinduced current in the device represents the dot product between a stored image and an image projected onto the first electrode. One-dimensional autocorrelations are performed by measuring this current while displacing the projected image.

  3. Ferroelectric optical image comparator

    DOEpatents

    Butler, M.A.; Land, C.E.; Martin, S.J.; Pfeifer, K.B.

    1993-11-30

    A ferroelectric optical image comparator has a lead lanthanum zirconate titanate thin-film device which is constructed with a semi-transparent or transparent conductive first electrode on one side of the thin film, a conductive metal second electrode on the other side of the thin film, and the second electrode is in contact with a nonconducting substrate. A photoinduced current in the device represents the dot product between a stored image and an image projected onto the first electrode. One-dimensional autocorrelations are performed by measuring this current while displacing the projected image. 7 figures.

  4. Compare Gene Profiles

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linuxmore » environment in serial or parallel mode.« less

  5. Comparator With Noise Suppression

    NASA Technical Reports Server (NTRS)

    Batts, C. N.

    1985-01-01

    Comparator continuously and automatically adjusts noise immunity period. High-gain amplifier used in conjunction with multivibrator 4 to provide clear pulse to multivibrator 1 at first negative-going zero crossing of input signal. Once multivibrator 1 cleared, output goes to zero volts and not retriggered until next time positive input exceeds reference level. Since input signal noise at zero crossing does not exceed reference level, no effect on multivibrator 1 operation. Circuit fabricated using standard solid-state operational amplifiers, multivibrators, OR gates, and passive elements.

  6. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs

    PubMed Central

    Zhou, Lufang; Cabrera, Marco E; Huang, Hazel; Yuan, Celvie L; Monika, Duda K; Sharma, Naveen; Bian, Fang; Stanley, William C

    2007-01-01

    Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fatty acid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction. Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively, but ATP and ADP concentrations did not change. NADH-generating pathways were rapidly activated in both the cytosol and mitochondria, as seen in a 40% depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase, and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental computational model of cardiac energy metabolism predicted that parallel activation of glycolysis and mitochondrial metabolism results in an increase in the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was observed. In conclusion, in the transition to a high cardiac workload there is rapid parallel activation of substrate oxidation that results in an increase in the NADH/NAD+ ratio. PMID:17185335

  7. Manipulator comparative testing program

    SciTech Connect

    Draper, J.V.; Handel, S.J.; Sundstrom, E.; Herndon, J.N.; Fujita, Y.; Maida, M.

    1986-01-01

    The Manipulator Comparative Testing Program compared performance of selected manipulator systems under typical remote handling conditions. The site of testing was the Remote Operations and Maintenance Demonstration Facility operated by the Consolidated Fuel Reprocessing Program of the Oak Ridge National Laboratory. Three experiment examined differences among manipulator systems from the US and Japan. The manipulator systems included the Meidensha BILARM 83A, Central Research Laboratories' (CRL's) Model M-2, and GCA PaR systems Model 6000. Six manipulator and control mode combinations were evaluated: (a) the BILARM in master-slave mode without force reflection; (b) the BILARM in master-slave mode with force reflection; (c) the Model M-2 in master-slave mode without force reflection; (d) the Model M-2 in master-slave mode with force reflection; (e) the BILARM with switchbox controls; and (f) the PaR 6000 with switchbox controls. The experiments also examined differences between master-slave systems with and without force reflections, and differences between master-slave systems and switchbox-controlled systems.

  8. Comparability of IQ Scores over Time

    ERIC Educational Resources Information Center

    Must, Olev; te Nijenhuis, Jan; Must, Aasa; van Vianen, Annelies E. M.

    2009-01-01

    This study investigates the comparability of IQ scores. Three cohorts (1933/36, 1997/98, 2006) of Estonian students (N = 2173) are compared using the Estonian National Intelligence Test. After 72 years the secular rise of the IQ test scores is 0.79 SD. The mean 0.16 SD increase in the last 8 years suggests a rapid increase of the Flynn Effect (FE)…

  9. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin

    PubMed Central

    Ramirez, Horacio A.; Liang, Liang; Pastar, Irena; Rosa, Ashley M.; Stojadinovic, Olivera; Zwick, Thomas G.; Kirsner, Robert S.; Maione, Anna G.; Garlick, Jonathan A.; Tomic-Canic, Marjana

    2015-01-01

    Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular

  10. Comparative and International Education: A Bibliography (2014)

    ERIC Educational Resources Information Center

    Comparative Education Review, 2015

    2015-01-01

    The 2014 "Comparative Education Review" bibliography of refereed journal articles on topics relevant to comparative and international education covers all 12 months in 2014 and includes 3,389 entries--a full 30 percent increase over the set of references assembled in the 2013 bibliography. They are drawn from 280 refereed journals, both…

  11. Poverty in Ireland in Comparative European Perspective

    ERIC Educational Resources Information Center

    Whelan, Christopher T.; Maitre, Bertrand

    2010-01-01

    In this paper we seek to put Irish poverty rates in a comparative European context. We do so in a context whereby the Irish economic boom and EU enlargement have led to increasing reservations being expressed regarding rates deriving from the EU "at risk of poverty" indicator. Our comparative analysis reports findings for both overall levels of…

  12. Data in support of comparative physiology and proteomic analysis of two wheat genotypes contrasting in drought tolerance.

    PubMed

    Faghani, Elham; Gharechahi, Javad; Komatsu, Setsuko; Mirzaei, Mehdi; Ali Khavarinejad, Ramzan; Najafi, Farzaneh; Karimi Farsad, Laleh; Salekdeh, Ghasem Hosseini

    2015-03-01

    Here, we present the data from a comparative physiology and proteomics approach used to analyze the response of two wheat genotypes (SERI M 82 (SE) and SW89.5193/kAu2 (SW)) with contrasting responses to drought stress. Proteomic analysis resulted in identification of 49 unique proteins with significant change in abundance (2-fold) under water shortage in roots and leaves. Gene ontology analysis of drought-responsive proteins (DRPs) suggested an induction of proteins related to cell wall biogenesis, ATP synthesis, photosynthesis, and carbohydrate/energy metabolism in leaves under stress condition. A large fraction of root proteins were identified to be involved in defense and oxidative stress response. In addition, a significant change was detected in proteins related to protein synthesis, ATP synthesis, and germin-like proteins in response to drought stress. A detailed analysis of this data may be obtained from Ref. [1]. PMID:26217700

  13. Comparative Effectiveness Research in Oncology

    PubMed Central

    2013-01-01

    Although randomized controlled trials represent the gold standard for comparative effective research (CER), a number of additional methods are available when randomized controlled trials are lacking or inconclusive because of the limitations of such trials. In addition to more relevant, efficient, and generalizable trials, there is a need for additional approaches utilizing rigorous methodology while fully recognizing their inherent limitations. CER is an important construct for defining and summarizing evidence on effectiveness and safety and comparing the value of competing strategies so that patients, providers, and policymakers can be offered appropriate recommendations for optimal patient care. Nevertheless, methodological as well as political and social challenges for CER remain. CER requires constant and sophisticated methodological oversight of study design and analysis similar to that required for randomized trials to reduce the potential for bias. At the same time, if appropriately conducted, CER offers an opportunity to identify the most effective and safe approach to patient care. Despite rising and unsustainable increases in health care costs, an even greater challenge to the implementation of CER arises from the social and political environment questioning the very motives and goals of CER. Oncologists and oncology professional societies are uniquely positioned to provide informed clinical and methodological expertise to steer the appropriate application of CER toward critical discussions related to health care costs, cost-effectiveness, and the comparative value of the available options for appropriate care of patients with cancer. PMID:23697601

  14. Comparative optimism about healthy eating.

    PubMed

    Sproesser, Gudrun; Klusmann, Verena; Schupp, Harald T; Renner, Britta

    2015-07-01

    The present study investigated people's perception of their own as compared to their peers' healthy eating and related these perceptions to actual healthy eating, BMI, and subsequent healthy eating behavior. Data were collected within the framework of the longitudinal cohort study Konstanz Life Study (T1: N = 770; T2: N = 510). Our results demonstrated an optimistic bias on the group level. Specifically, people rated their own eating behavior as healthier on average than that of their average peers. This comparative optimism occurred even when actual healthy eating was unfavorable and BMI was high. However, it increased with actual healthy eating behavior. Importantly, optimistic perceptions were positively related to the intention to eat healthily and healthy eating six months later. Hence, the results suggest that an optimistic comparative view of one's own healthy eating is grounded in reality and boosts rather than deters subsequent health behavior. This implies that there might not be a need to reduce optimistic perceptions of healthy eating behavior.

  15. Comparing Resource Adequacy Metrics

    SciTech Connect

    Ibanez, Eduardo; Milligan, Michael

    2014-11-13

    As the penetration of variable generation (wind and solar) increases around the world, there is an accompanying growing interest and importance in accurately assessing the contribution that these resources can make toward planning reserve. This contribution, also known as the capacity credit or capacity value of the resource, is best quantified by using a probabilistic measure of overall resource adequacy. In recognizing the variable nature of these renewable resources, there has been interest in exploring the use of reliability metrics other than loss of load expectation. In this paper, we undertake some comparisons using data from the Western Electricity Coordinating Council in the western United States.

  16. Comparative Magma Oceanography

    NASA Technical Reports Server (NTRS)

    Jones, John H.

    1999-01-01

    The question of whether the Earth ever passed through a magma ocean stop is of considerable interest. Geochemical evidence strongly suggests that the Moon had a magma ocean and the evidence is mounting that the same was true for Mars. Analyses of mar (SNC) meteorites have yielded insights into the differentiation history of Mars, and consequently, it is interesting to compare that planet to the Earth. Three primary features of An contrast strongly to those of the Earth: (1) the extremely ancient ages of the martian core, mantle, and crust (approx. 4.55 b.y.); (2) the highly depleted nature of the martian mantle; and (3) the extreme ranges of Nd isotopic compositions that arise within the crust and depleted mantle.

  17. Manipulator comparative testing program

    SciTech Connect

    Draper, J.V.; Handel, S.J.; Sundstrom, E.; Herndon, J.N.; Fujita, Y.; Maeda, M.

    1986-01-01

    The Manipulator Comparative Testing Program examined differences among manipulator systems from the United States and Japan. The manipulator systems included the Meidensha BILARM 83A, the Model M-2 of Central Research Laboratories Division of Sargent Industries (CRL), and the GCA Corporation PaR Systems Model 6000. The site of testing was the Remote Operations Maintenance Demonstration (ROMD) facility, operated by the Fuel Recycle Division in the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory (ORNL). In all stages of testing, operators using the CRL Model M-2 manipulator had consistently lower times to completion and error rates than they did using other machines. Performance was second best with the Meidensha BILARM 83A in master-slave mode. Performance with the BILARM in switchbox mode and the PaR 6000 manipulator was approximately equivalent in terms of criteria recorded in testing. These data show no impact of force reflection on task performance.

  18. Terminological Comparability as a Factor in Increasing International Mobility in the Sphere of Higher Education.

    ERIC Educational Resources Information Center

    Kuznetsov, V. M.; And Others

    1986-01-01

    Mutual understanding and the strengthening of ties among the higher education systems of different countries depends largely on overcoming language barriers, and the national and international standardization of terminology would help in that process. (MSE)

  19. Susceptibility to the Flash-Beep Illusion Is Increased in Children Compared to Adults

    ERIC Educational Resources Information Center

    Innes-Brown, Hamish; Barutchu, Ayla; Shivdasani, Mohit N.; Crewther, David P.; Grayden, David B.; Paolini, Antonio

    2011-01-01

    Audio-visual integration was studied in children aged 8-17 (N = 30) and adults (N = 22) using the "flash-beep illusion" paradigm, where the presentation of two beeps causes a single flash to be perceived as two flashes ("fission" illusion), and a single beep causes two flashes to be perceived as one flash ("fusion" illusion). Children reported…

  20. Comparing Two Training Strategies to Increase Competence in Solving Ethical Dilemmas

    ERIC Educational Resources Information Center

    Garcia, Jorge; Froehlic, Robert; McGuire-Kuletz, Maureen; Rejiester, Nicole

    2009-01-01

    This study examined which of two training models delivered through the internet led to better cultural competence in resolving ethical dilemmas with a sample of rehabilitation professionals. One type of training involved teaching a transcultural integrative model of ethical decision-making while the other training involved using the same…

  1. Increasing FCC regenerator catalyst level

    SciTech Connect

    Wong, R.F. )

    1993-11-01

    A Peruvian FCC unit's operations were improved by increasing the regenerator's catalyst level. This increase resulted in lower stack losses, an improved temperature profile, increased catalyst activity and a lower catalyst consumption rate. A more stable operation saved this Peruvian refiner over $131,000 per year in catalyst alone. These concepts and data may be suitable for your FCC unit as well.

  2. Trifluoperazine increases fatty acid turnover in phospholipids in cultured human fibroblasts.

    PubMed

    Mazière, C; Mazière, J C; Mora, L; Auclair, M; Polonovski, J

    1988-05-01

    A 24-hr pretreatment of cultured human fibroblasts with trifluoperazine induced a marked increase in incorporation of saturated (stearic, palmitic) and unsaturated (oleic, arachidonic) fatty acids into phospholipids (1.5- to 2-fold for 5.10(-5) M trifluoperazine). Concomitantly, incorporation into cholesteryl esters was strongly inhibited (20% of control for 5.10(-5) M trifluoperazine). The drug did not change the phospholipid composition of treated cells. The effect of trifluoperazine on oleic acid incorporation into phospholipids was time-dependent and reached a maximum after a six-hr preincubation with the drug. Trifluoperazine also induced an increase in the rate of chase of oleic acid from the different phospholipid classes. In vitro preincubation of cell-free extracts with trifluoperazine resulted in activation of phospholipid acyltransferases, whereas cholesterol acyltransferase activity was decreased. The rapid effect of trifluoperazine together with its effect on a cell-free system suggests a direct action of this amphiphilic drug on the acyltransferase activities, probably by modification of the structural organization of cellular membranes.

  3. Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis.

    PubMed

    Gardi, C; Bauerova, K; Stringa, B; Kuncirova, V; Slovak, L; Ponist, S; Drafi, F; Bezakova, L; Tedesco, I; Acquaviva, A; Bilotto, S; Russo, G L

    2015-10-01

    Novel therapies for rheumatoid arthritis also include the use of naturally occurring compounds possessing antioxidant properties. In the present work, the effects of oral administration of quercetin were investigated in a rat model of adjuvant arthritis. Arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experimental groups were treated with an oral daily dose of 150 mg/kg b.w. of quercetin for 28 days. Results indicated that quercetin was able to ameliorate all markers of inflammation and oxidative stress measured. Quercetin lowered levels of interleukin-1β, C-reactive protein, and monocyte chemotactic protein-1 and restored plasma antioxidant capacity. In addition, quercetin inhibited the enzymatic activity of pro-inflammatory 12/15-lipoxygenase in lung and liver and increased the expression of heme oxygenase-1 in joint and lung of arthritic rats. Finally, quercetin inhibited the 2-fold increase of NF-қB activity observed in lung, liver and joint after induction of arthritis. PMID:26297952

  4. Corn stover harvest increases herbicide movement to subsurface drains: RZWQM simulations

    USGS Publications Warehouse

    Shipitalo, Martin J.; Malone, Robert W.; Ma, Liwang; Nolan, Bernard T.; Kanwar, Rameshwar S.; Shaner, Dale L.; Pederson, Carl H.

    2016-01-01

    BACKGROUND Crop residue removal for bioenergy production can alter soil hydrologic properties and the movement of agrochemicals to subsurface drains. The Root Zone Water Quality Model (RZWQM), previously calibrated using measured flow and atrazine concentrations in drainage from a 0.4 ha chisel-tilled plot, was used to investigate effects of 50 and 100% corn (Zea mays L.) stover harvest and the accompanying reductions in soil crust hydraulic conductivity and total macroporosity on transport of atrazine, metolachlor, and metolachlor oxanilic acid (OXA). RESULTS The model accurately simulated field-measured metolachlor transport in drainage. A 3-yr simulation indicated that 50% residue removal decreased subsurface drainage by 31% and increased atrazine and metolachlor transport in drainage 4 to 5-fold when surface crust conductivity and macroporosity were reduced by 25%. Based on its measured sorption coefficient, ~ 2-fold reductions in OXA losses were simulated with residue removal. CONCLUSION RZWQM indicated that if corn stover harvest reduces crust conductivity and soil macroporosity, losses of atrazine and metolachlor in subsurface drainage will increase due to reduced sorption related to more water moving through fewer macropores. Losses of the metolachlor degradation product OXA will decrease due to the more rapid movement of the parent compound into the soil.

  5. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    PubMed Central

    Hansen, M. E.; Tippetts, T. S.; Anderson, M. C.; Holub, Z. E.; Moulton, E. R.; Swensen, A. C.; Prince, J. T.; Bikman, B. T.

    2014-01-01

    Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects. PMID:24949486

  6. Comparing Mutational Variabilities

    PubMed Central

    Houle, D.; Morikawa, B.; Lynch, M.

    1996-01-01

    We have reviewed the available data on V(M), the amount of genetic variation in phenotypic traits produced each generation by mutation. We use these data to make several qualitative tests of the mutation-selection balance hypothesis for the maintenance of genetic variance (MSB). To compare V(M) values, we use three dimensionless quantities: mutational heritability, V(M)/V(E); the mutational coefficient of variation, CV(M); and the ratio of the standing genetic variance to V(M), V(G)/V(M). Since genetic coefficients of variation for life history traits are larger than those for morphological traits, we predict that under MSB, life history traits should also have larger CV(M). This is confirmed; life history traits have a median CV(M) value more than six times higher than that for morphological traits. V(G)/V(M) approximates the persistence time of mutations under MSB in an infinite population. In order for MSB to hold, V(G)/V(M) must be small, substantially less than 1000, and life history traits should have smaller values than morphological traits. V(G)/V(M) averages about 50 generations for life history traits and 100 generations for morphological traits. These observations are all consistent with the predictions of a mutation-selection balance model. PMID:8807316

  7. Comparative ISS accelerometric analyses

    NASA Astrophysics Data System (ADS)

    Sáez, N.; Ruiz, X.; Gavaldà, Jna.; Pallarés, J.; Shevtsova, V.

    2014-02-01

    Two accelerometric records coming from the SAMSes es08 sensor in the Columbus module, the so-called Runs 14 and 33 in terms of the IVIDIL experiment, has been studied here using standard digital signal analysis techniques. The principal difference between both records is the vibrational state of the IVIDIL experiment, that is to say, during Run 14 the shaking motor of the experiment is active while that in Run 33 this motor is stopped. Identical procedures have been applied to a third record coming from the SAMSII 121f03 sensor located in the Destiny module during an IVIDIL quiescent period. All records have been downloaded from the corresponding public binary accelerometric files from the NASA Principal Investigator Microgravity Services, PIMS website and, in order to be properly compared, have the same number of data. Results detect clear differences in the accelerometric behavior, with or without shaking, despite the care of the designers to ensure the achievement of the ISS μg-vibrational requirements all along the experiments.

  8. Comparing Two Satellite Sensors

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This pair of images shows the same area of South Africa's Kruger National Park taken by different satellite sensors only minutes apart. The top image is from the Enhanced Thematic Mapper plus (ETM+) aboard Landsat 7, the latest in a long line of high-resolution remote sensing satellites begun in 1972 with the Earth Resources Technology Satellite (ERTS), later renamed Landsat-1. The bottom image was acquired by the Advanced Land Imager (ALI) aboard Earth Observer-1 (EO-1), an instrument designed to test new technologies that will continue the observations begun by the Landsat satellites. Future instruments like the ALI will be much smaller and less expensive than the ETM+, enabling NASA and the United States Geological Survey (USGS) to continue exploring the surface of the Earth. Both images above are false color composites combining short wave infrared (1.65 um), near infrared (.79 um), and green (.57 um) wavelengths as red, green, and blue, respectively. Dense vegetation appears green. The similarity of the images demonstrates the ability of the ALI to produce data that can be compared with the 29-year archive of Landsat data. Several NASA field campaigns conducted in Kruger National Park provided ground-based data needed to evaluate measurements from each of the satellite sensors. For more information, read the EO-1 fact sheet and the Landsat-7 fact sheet. Images courtesy Landsat 7 Science Team

  9. Ecotoxicogenomics: Microarray interlaboratory comparability.

    PubMed

    Vidal-Dorsch, Doris E; Bay, Steven M; Moore, Shelly; Layton, Blythe; Mehinto, Alvine C; Vulpe, Chris D; Brown-Augustine, Marianna; Loguinov, Alex; Poynton, Helen; Garcia-Reyero, Natàlia; Perkins, Edward J; Escalon, Lynn; Denslow, Nancy D; Cristina, Colli-Dula R; Doan, Tri; Shukradas, Shweta; Bruno, Joy; Brown, Lorraine; Van Agglen, Graham; Jackman, Paula; Bauer, Megan

    2016-02-01

    Transcriptomic analysis can complement traditional ecotoxicology data by providing mechanistic insight, and by identifying sub-lethal organismal responses and contaminant classes underlying observed toxicity. Before transcriptomic information can be used in monitoring and risk assessment, it is necessary to determine its reproducibility and detect key steps impacting the reliable identification of differentially expressed genes. A custom 15K-probe microarray was used to conduct transcriptomics analyses across six laboratories with estuarine amphipods exposed to cyfluthrin-spiked or control sediments (10 days). Two sample types were generated, one consisted of total RNA extracts (Ex) from exposed and control samples (extracted by one laboratory) and the other consisted of exposed and control whole body amphipods (WB) from which each laboratory extracted RNA. Our findings indicate that gene expression microarray results are repeatable. Differentially expressed data had a higher degree of repeatability across all laboratories in samples with similar RNA quality (Ex) when compared to WB samples with more variable RNA quality. Despite such variability a subset of genes were consistently identified as differentially expressed across all laboratories and sample types. We found that the differences among the individual laboratory results can be attributed to several factors including RNA quality and technical expertise, but the overall results can be improved by following consistent protocols and with appropriate training.

  10. Ebolavirus comparative genomics

    DOE PAGES

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; et al

    2015-07-14

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. We examine the dynamics of this genome, comparing more than one hundred currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus, and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of themore » same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP), and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. In conclusion, this information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies.« less

  11. Is asthma prevalence still increasing?

    PubMed

    Lundbäck, Bo; Backman, Helena; Lötvall, Jan; Rönmark, Eva

    2016-01-01

    Increased awareness of asthma in society and altered diagnostic practices makes evaluation of data on prevalence change difficult. In most parts of the world the asthma prevalence seems to still be increasing. The increase is associated with urbanization and has been documented particularly among children and teenagers in urban areas of middle- and low-level income countries. Use of validated questionnaires has enabled comparisons of studies. Among adults there are few studies based on representative samples of the general population which allow evaluation of time trends of prevalence. This review focuses mainly on studies of asthma prevalence and symptoms among adults. Parallel with increased urbanization, we can assume that the increase in asthma prevalence in most areas of the world will continue. However, in Australia and North-West Europe studies performed, particularly among children and adolescents, indicate that the increase in asthma prevalence may now be leveling off. PMID:26610152

  12. Comparative waste forms study

    SciTech Connect

    Wald, J.W.; Lokken, R.O.; Shade, J.W.; Rusin, J.M.

    1980-12-01

    A number of alternative process and waste form options exist for the immobilization of nuclear wastes. Although data exists on the characterization of these alternative waste forms, a straightforward comparison of product properties is difficult, due to the lack of standardized testing procedures. The characterization study described in this report involved the application of the same volatility, mechanical strength and leach tests to ten alternative waste forms, to assess product durability. Bulk property, phase analysis and microstructural examination of the simulated products, whose waste loading varied from 5% to 100% was also conducted. The specific waste forms investigated were as follows: Cold Pressed and Sintered PW-9 Calcine; Hot Pressed PW-9 Calcine; Hot Isostatic Pressed PW-9 Calcine; Cold Pressed and Sintered SPC-5B Supercalcine; Hot Isostatic pressed SPC-5B Supercalcine; Sintered PW-9 and 50% Glass Frit; Glass 76-68; Celsian Glass Ceramic; Type II Portland Cement and 10% PW-9 Calcine; and Type II Portland Cement and 10% SPC-5B Supercalcine. Bulk property data were used to calculate and compare the relative quantities of waste form volume produced at a spent fuel processing rate of 5 metric ton uranium/day. This quantity ranged from 3173 L/day (5280 Kg/day) for 10% SPC-5B supercalcine in cement to 83 L/day (294 Kg/day) for 100% calcine. Mechanical strength, volatility, and leach resistance tests provide data related to waste form durability. Glass, glass-ceramic and supercalcine ranked high in waste form durability where as the 100% PW-9 calcine ranked low. All other materials ranked between these two groupings.

  13. Ebolavirus comparative genomics

    PubMed Central

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S.; Pedersen, Thomas D.; Wassenaar, Trudy M.; Ussery, David W.

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). PMID:26175035

  14. Loving-kindness meditation increases social connectedness.

    PubMed

    Hutcherson, Cendri A; Seppala, Emma M; Gross, James J

    2008-10-01

    The need for social connection is a fundamental human motive, and it is increasingly clear that feeling socially connected confers mental and physical health benefits. However, in many cultures, societal changes are leading to growing social distrust and alienation. Can feelings of social connection and positivity toward others be increased? Is it possible to self-generate these feelings? In this study, the authors used a brief loving-kindness meditation exercise to examine whether social connection could be created toward strangers in a controlled laboratory context. Compared with a closely matched control task, even just a few minutes of loving-kindness meditation increased feelings of social connection and positivity toward novel individuals on both explicit and implicit levels. These results suggest that this easily implemented technique may help to increase positive social emotions and decrease social isolation.

  15. Increased aldosterone: mechanism of hypertension in obesity.

    PubMed

    Flynn, Colleen

    2014-05-01

    The prevalence of both obesity and hypertension are increasing worldwide. Hypertension is a common consequence of obesity. Increased central adiposity is associated with increased aldosterone levels and blood pressure in human beings. A number of small studies have shown an association between obesity-mediated hypertension and mechanisms directly linked to increased levels of aldosterone. These studies have shown a trend toward relatively greater blood pressure reduction using aldosterone-receptor blockers compared with other classes of antihypertensive agents. Other than treatment for weight loss, treatment of hypertension with specific antihypertensive medications that block or reduce aldosterone action are appropriate in obese patients. Further research is needed to understand the exact role of the adipocyte in obesity-mediated hypertension.

  16. Comparative Digestive Physiology

    PubMed Central

    Karasov, William H.; Douglas, Angela E.

    2015-01-01

    In vertebrates and invertebrates, morphological and functional features of gastrointestinal (GI) tracts generally reflect food chemistry, such as content of carbohydrates, proteins, fats, and material(s) refractory to rapid digestion (e.g., cellulose). The expression of digestive enzymes and nutrient transporters approximately matches the dietary load of their respective substrates, with relatively modest excess capacity. Mechanisms explaining differences in hydrolase activity between populations and species include gene copy number variations and single-nucleotide polymorphisms. Transcriptional and posttranscriptional adjustments mediate phenotypic changes in the expression of hydrolases and transporters in response to dietary signals. Many species respond to higher food intake by flexibly increasing digestive compartment size. Fermentative processes by symbiotic microorganisms are important for cellulose degradation but are relatively slow, so animals that rely on those processes typically possess special enlarged compartment(s) to maintain a microbiota and other GI structures that slow digesta flow. The taxon richness of the gut microbiota, usually identified by 16S rRNA gene sequencing, is typically an order of magnitude greater in vertebrates than invertebrates, and the interspecific variation in microbial composition is strongly influenced by diet. Many of the nutrient transporters are orthologous across different animal phyla, though functional details may vary (e.g., glucose and amino acid transport with K+ rather than Na+ as a counter ion). Paracellular absorption is important in many birds. Natural toxins are ubiquitous in foods and may influence key features such as digesta transit, enzymatic breakdown, microbial fermentation, and absorption PMID:23720328

  17. Increasing point-count duration increases standard error

    USGS Publications Warehouse

    Smith, W.P.; Twedt, D.J.; Hamel, P.B.; Ford, R.P.; Wiedenfeld, D.A.; Cooper, R.J.

    1998-01-01

    We examined data from point counts of varying duration in bottomland forests of west Tennessee and the Mississippi Alluvial Valley to determine if counting interval influenced sampling efficiency. Estimates of standard error increased as point count duration increased both for cumulative number of individuals and species in both locations. Although point counts appear to yield data with standard errors proportional to means, a square root transformation of the data may stabilize the variance. Using long (>10 min) point counts may reduce sample size and increase sampling error, both of which diminish statistical power and thereby the ability to detect meaningful changes in avian populations.

  18. Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat

    SciTech Connect

    Kaiser, C.A.; Seydoux, J.; Giacobino, J.P.; Girardier, L.; Burger, A.G.

    1988-03-01

    In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation.

  19. Increased airway glucose increases airway bacterial load in hyperglycaemia.

    PubMed

    Gill, Simren K; Hui, Kailyn; Farne, Hugo; Garnett, James P; Baines, Deborah L; Moore, Luke S P; Holmes, Alison H; Filloux, Alain; Tregoning, John S

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  20. Increased airway glucose increases airway bacterial load in hyperglycaemia

    PubMed Central

    Gill, Simren K.; Hui, Kailyn; Farne, Hugo; Garnett, James P.; Baines, Deborah L.; Moore, Luke S.P.; Holmes, Alison H.; Filloux, Alain; Tregoning, John S.

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  1. Elevated atmospheric carbon dioxide increases soil carbon

    SciTech Connect

    Norby, Richard J; Jastrow, Julie D; Miller, Michael R; Matamala, Roser; Boutton, Thomas W; Rice, Charles W; Owensby, Clenton E

    2005-01-01

    In a study funded by the U.S. Department of Energy's Office of Science, researchers from Argonne and Oak Ridge National Laboratories and Kansas State and Texas A&M Universities evaluated the collective results of earlier studies by using a statistical procedure called meta-analysis. They found that on average elevated CO2 increased soil carbon by 5.6 percent over a two to nine year period. They also measured comparable increases in soil carbon for Tennessee deciduous forest and Kansas grassland after five to eight years of experimental exposure to elevated CO2.

  2. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  3. Increased hedonic differences despite increases in hedonic range.

    PubMed

    Zellner, Debra A; Jones, Ke'Nesha; Morino, Jennifer; Cogan, Elizabeth S; Jennings, Emily M; Parker, Scott

    2010-07-01

    Viewing hedonically negative paintings increased the hedonic ratings of subsequently viewed test paintings (positive hedonic contrast; Experiment 1) and also increased the degree of preference between the test paintings (Experiments 2 and 3). This result differs from the reduction in hedonic preference (hedonic condensation) that accompanies negative hedonic contrast. It also differs from the reduction in perceived differences that usually accompanies expansion of stimulus range and that is predicted by numerous theories.

  4. Volatiles Which Increase Magma Viscosity

    NASA Astrophysics Data System (ADS)

    Webb, S.

    2015-12-01

    The standard model of an erupting volcano is one in which the viscosity of a decompressing magma increases as the volatiles leave the melt structure to form bubbles. It has now been observed that the addition of the "volatiles" P, Cl and F result in an increase in silicate melt viscosity. This observation would mean that the viscosity of selected degassing magmas would decrease rather than increase. Here we look at P, Cl and F as three volatiles which increase viscosity through different structural mechanisms. In all three cases the volatiles increase the viscosity of peralkaline composition melts, but appear to always decrease the viscosity of peraluminous melts. Phosphorus causes the melt to unmix into a Na-P rich phase and a Na-poor silicate phase. Thus as the network modifying Na (or Ca) are removed to the phosphorus-rich melt, the matrix melt viscosity increases. With increasing amounts of added phosphorus (at network modifying Na ~ P) the addition of further phosphorus causes a decrease in viscosity. The addition of chlorine to Fe-free aluminosilicate melts results in an increase in viscosity. NMR data on these glass indicates that the chlorine sits in salt-like structures surrounded by Na and/or Ca. Such structures would remove network-modifying atoms from the melt structure and thus result in an increase in viscosity. The NMR spectra of fluorine-bearing glasses shows that F takes up at least 5 different structural positions in peralkaline composition melts. Three of these positions should result in a decrease in viscosity due to the removal of bridging oxygens. Two of the structural positons of F, however, should result in an increase in viscosity as they require the removal of network-modifying atoms from the melt structure (with one of the structures being that observed for Cl). This would imply that increasing amounts of F might result in an increase in viscosity. This proposed increase in viscosity with increasing F has now been experimentally confirmed.

  5. Comparative effectiveness in esophagogastric cancer.

    PubMed

    Knab, Lawrence M; Belotte, Jim; Munshi, Hidayatullah G; Bentrem, David J

    2015-01-01

    Cancer of the esophagus and the gastroesophageal junction (GEJ) continues to have a dismal prognosis, with the incidence of esophageal cancer increasing in the United States. Although radical resection was initially the primary treatment for this disease process, systemic chemotherapy and radiation have been shown to play a role in prolonging survival in most patient populations. This chapter explores the evidence that guides treatment for esophageal and GEJ cancer today. Chemotherapy and radiation therapy were introduced as treatment modalities for esophageal and GEJ cancers when it became evident that surgical therapy alone provided poor long-term survival rates. A variety of treatment strategies have been explored including preoperative (neoadjuvant) and postoperative (adjuvant) chemotherapy, with and without radiation. The evidence suggests that neoadjuvant chemotherapy or chemoradiotherapy provides better outcomes compared to surgery alone for esophageal, GEJ, and gastric cancers. Studies indicate a trend towards improved survival when neoadjuvant chemoradiotherapy is compared to chemotherapy alone. When patients have undergone resection with node-positive disease without receiving neoadjuvant therapy, some form of adjuvant treatment is recommended. This chapter also explores the surgical management of esophageal, GEJ, and gastric cancers including the extent of the gastric lymph node dissection. It also includes a discussion about adherence to national guidelines in terms of gastric cancer treatment and esophageal and gastric lymph node examinations.

  6. Increasing hope by addressing clients' outcome expectations.

    PubMed

    Swift, Joshua K; Derthick, Annie O

    2013-09-01

    Addressing clients' outcome expectations is an important clinical process that can lead to a strong therapeutic alliance, more positive treatment outcomes, and decreased rates of premature termination from psychotherapy. Five interventions designed to foster appropriate outcome expectations are discussed, including presenting a convincing treatment rationale, increasing clients' faith in their therapists, expressing faith in clients, providing outcome education, and comparing progress with expectations. Clinical examples and research support are provided for each. PMID:24000836

  7. Increased gasoline octane in FCC reactor

    SciTech Connect

    Beech, J.H.; Gross, B.; Ramage, M.P.

    1984-07-10

    The operation of FCC apparatus is improved by decreasing oil partial pressure in the FCC reactor riser by about 10 psia, as compared to the normal oil partial pressure in the riser, thereby increasing octane rating of the gasoline produced in the FCC unit. The oil partial pressure may be reduced by injecting a suitable amount of an inert diluent into the riser, or by decreasing throughput of the FCC reactor.

  8. Comparative Magma Oceanography

    NASA Technical Reports Server (NTRS)

    Jones, J. H.

    1999-01-01

    The question of whether the Earth ever passed through a magma ocean stage is of considerable interest. Geochemical evidence strongly suggests that the Moon had a magma ocean and the evidence is mounting that the same was true for Mars. Analyses of martian (SNC) meteorites have yielded insights into the differentiation history of Mars, and consequently, it is interesting to compare that planet to the Earth. Three primary features of Mars contrast strongly to those of the Earth: (i) the extremely ancient ages of the martian core, mantle, and crust (about 4.55 b.y.); (ii) the highly depleted nature of the martian mantle; and (iii) the extreme ranges of Nd isotopic compositions that arise within the crust and depleted mantle. The easiest way to explain the ages and diverse isotopic compositions of martian basalts is to postulate that Mars had an early magma ocean. Cumulates of this magma ocean were later remelted to form the SNC meteorite suite and some of these melts assimilated crustal materials enriched in incompatible elements. The REE pattern of the crust assimilated by these SNC magmas was LREE enriched. If this pattern is typical of the crust as a whole, the martian crust is probably similar in composition to melts generated by small degrees of partial melting (about 5%) of a primitive source. Higher degrees of partial melting would cause the crustal LREE pattern to be essentially flat. In the context of a magma ocean model, where large degrees of partial melting presumably prevailed, the crust would have to be dominated by late-stage, LREE-enriched residual liquids. Regardless of the exact physical setting, Nd and W isotopic evidence indicates that martian geochemical reservoirs must have formed early and that they have not been efficiently remixed since. The important point is that in both the Moon and Mars we see evidence of a magma ocean phase and that we recognize it as such. Several lines of theoretical inference point to an early Earth that was also hot

  9. Increasing diversity in radiologic technology.

    PubMed

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity. PMID:14671827

  10. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

    PubMed

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-04-29

    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.

  11. Hypothermia Increases Tissue Plasminogen Activator Expression and Decreases Post-Operative Intra-Abdominal Adhesion

    PubMed Central

    Lee, Chien-Chang; Wang, Hsuan-Mao; Chou, Tzung-Hsin; Wu, Meng-Che; Hsueh, Kuang-Lung; Chen, Shyr-Chyr

    2016-01-01

    Background Therapeutic hypothermia during operation decreases postoperative intra-abdominal adhesion formation. We sought to determine the most appropriate duration of hypothermia, and whether hypothermia affects the expression of tissue plasminogen activator (tPA). Methods 80 male BALB/c mice weighing 25–30 g are randomized into one of five groups: adhesion model with infusion of 15°C saline for 15 minutes (A); 30 minutes (B); 45 minute (C); adhesion model without infusion of cold saline (D); and sham operation without infusion of cold saline (E). Adhesion scores and tPA levels in the peritoneum fluid levels were analyzed on postoperative days 1, 7, and 14. Results On day 14, the cold saline infusion groups (A, B, and C) had lower adhesion scores than the without infusion of cold saline group (D). However, only group B (cold saline infusion for 30 minutes) had a significantly lower adhesion scores than group D. Also, group B was found to have 3.4 fold, 2.3 fold, and 2.2 fold higher levels of tPA than group D on days 1, 7, and 14 respectively. Conclusions Our results suggest that cold saline infusion for 30 minutes was the optimum duration to decrease postoperative intra-abdominal adhesion formation. The decrease in the adhesion formations could be partly due to an increase in the level of tPA. PMID:27583464

  12. Different Resistance-Training Regimens Evoked a Similar Increase in Myostatin Inhibitors Expression.

    PubMed

    Santos, A R; Lamas, L; Ugrinowitsch, C; Tricoli, V; Miyabara, E H; Soares, A G; Aoki, M S

    2015-08-01

    The aim of the present study was to investigate the effect of different resistance-training regimens (S or P) on the expression of genes related to the MSTN signaling pathway in physically-active men. 29 male subjects with at least 2 years of experience in strength training were assigned to either a strength-training group (S; n=11) or a power-training group (P; n=11). The control group (C; n=7) was composed of healthy physically-active males. The S and the P groups performed high- and low-intensity squats, respectively, 3 times per week, for 8 weeks. Muscle biopsies from the vastus lateralis muscle were collected before and after the training period. No change was observed in MSTN, ACTIIB, GASP-1 and FOXO-3 A gene expression after the training period. A similar increase in the gene expression of the inhibitory proteins of the MSTN signaling pathway, FLST (S: 4.2 fold induction and P: 3.7 fold induction, p<0.01) and FL-3 (S: 5.6 fold induction and P: 5.6 fold induction, p<0.01), was detected after the training period. SMAD-7 gene expression was similarly augmented after both training protocols (S: 2.5 fold induction; P: 2.8 fold induction; p<0.05). In conclusion, the resistance-training regimens (S and P) activated the expression of inhibitors of the MSTN signaling pathway in a similar manner. PMID:25822941

  13. Increasing Learning from TV News.

    ERIC Educational Resources Information Center

    Perloff, Richard M.; And Others

    1982-01-01

    Describes an experiment that manipulated two variables, repetition and pausing for viewer "digestion" of information in a news telecast. Concludes that the use of repetition increased viewers' retention of information, but that pauses did not. (FL)

  14. Clinton proposes science funding increase

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    President Bill Clinton proposed a major increase in science funding and several science and environment initiatives during his State of the Union address on January 28.As part of the White House Millennium Program the administration established to promote the nation's creativity and innovation, the President proposed a 21st Century Research Fund for scientific inquiry that would provide the largest one-year funding increase in history for the National Science Foundation (NSF), National Institutes of Health, and National Cancer Institute.

  15. Can improvement in photosynthesis increase crop yields?

    PubMed

    Long, Stephen P; Zhu, Xin-Guang; Naidu, Shawna L; Ort, Donald R

    2006-03-01

    The yield potential (Yp) of a grain crop is the seed mass per unit ground area obtained under optimum growing conditions without weeds, pests and diseases. It is determined by the product of the available light energy and by the genetically determined properties: efficiency of light capture (epsilon i), the efficiency of conversion of the intercepted light into biomass (epsilon c) and the proportion of biomass partitioned into grain (eta). Plant breeding brings eta7 and epsilon i close to their theoretical maxima, leaving epsilon c, primarily determined by photosynthesis, as the only remaining major prospect for improving Yp. Leaf photosynthetic rate, however, is poorly correlated with yield when different genotypes of a crop species are compared. This led to the viewpoint that improvement of leaf photosynthesis has little value for improving Yp. By contrast, the many recent experiments that compare the growth of a genotype in current and future projected elevated [CO2] environments show that increase in leaf photosynthesis is closely associated with similar increases in yield. Are there opportunities to achieve similar increases by genetic manipulation? Six potential routes of increasing epsilon c by improving photosynthetic efficiency were explored, ranging from altered canopy architecture to improved regeneration of the acceptor molecule for CO2. Collectively, these changes could improve epsilon c and, therefore, Y p by c. 50%. Because some changes could be achieved by transgenic technology, the time of the development of commercial cultivars could be considerably less than by conventional breeding and potentially, within 10-15 years.

  16. Pulsed electric field increases reproduction.

    PubMed

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

  17. Pulsed electric field increases reproduction.

    PubMed

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated. PMID:26651869

  18. Comparative Habitability of Transiting Exoplanets

    NASA Astrophysics Data System (ADS)

    Barnes, Rory; Meadows, Victoria S.; Evans, Nicole

    2015-12-01

    Exoplanet habitability is traditionally assessed by comparing a planet’s semimajor axis to the location of its host star’s “habitable zone,” the shell around a star for which Earth-like planets can possess liquid surface water. The Kepler space telescope has discovered numerous planet candidates near the habitable zone, and many more are expected from missions such as K2, TESS, and PLATO. These candidates often require significant follow-up observations for validation, so prioritizing planets for habitability from transit data has become an important aspect of the search for life in the universe. We propose a method to compare transiting planets for their potential to support life based on transit data, stellar properties and previously reported limits on planetary emitted flux. For a planet in radiative equilibrium, the emitted flux increases with eccentricity, but decreases with albedo. As these parameters are often unconstrained, there is an “eccentricity-albedo degeneracy” for the habitability of transiting exoplanets. Our method mitigates this degeneracy, includes a penalty for large-radius planets, uses terrestrial mass-radius relationships, and, when available, constraints on eccentricity to compute a number we call the “habitability index for transiting exoplanets” that represents the relative probability that an exoplanet could support liquid surface water. We calculate it for Kepler objects of interest and find that planets that receive between 60% and 90% of the Earth’s incident radiation, assuming circular orbits, are most likely to be habitable. Finally, we make predictions for the upcoming TESS and James Webb Space Telescope missions.

  19. COMPARATIVE HABITABILITY OF TRANSITING EXOPLANETS

    SciTech Connect

    Barnes, Rory; Meadows, Victoria S.; Evans, Nicole

    2015-12-01

    Exoplanet habitability is traditionally assessed by comparing a planet’s semimajor axis to the location of its host star’s “habitable zone,” the shell around a star for which Earth-like planets can possess liquid surface water. The Kepler space telescope has discovered numerous planet candidates near the habitable zone, and many more are expected from missions such as K2, TESS, and PLATO. These candidates often require significant follow-up observations for validation, so prioritizing planets for habitability from transit data has become an important aspect of the search for life in the universe. We propose a method to compare transiting planets for their potential to support life based on transit data, stellar properties and previously reported limits on planetary emitted flux. For a planet in radiative equilibrium, the emitted flux increases with eccentricity, but decreases with albedo. As these parameters are often unconstrained, there is an “eccentricity-albedo degeneracy” for the habitability of transiting exoplanets. Our method mitigates this degeneracy, includes a penalty for large-radius planets, uses terrestrial mass–radius relationships, and, when available, constraints on eccentricity to compute a number we call the “habitability index for transiting exoplanets” that represents the relative probability that an exoplanet could support liquid surface water. We calculate it for Kepler objects of interest and find that planets that receive between 60% and 90% of the Earth’s incident radiation, assuming circular orbits, are most likely to be habitable. Finally, we make predictions for the upcoming TESS and James Webb Space Telescope missions.

  20. Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight.

    PubMed

    Smith, Steven R; Lovejoy, Jennifer C; Bray, George A; Rood, Jennifer; Most, Marlene M; Ryan, Donna H

    2008-12-01

    Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.

  1. Thyrotropin-releasing Hormone Increases Behavioral Arousal Through Modulation of Hypocretin/Orexin Neurons

    PubMed Central

    Hara, Junko; Gerashchenko, Dmitry; Wisor, Jonathan P.; Sakurai, Takeshi; Xie, Xinmin (Simon); Kilduff, Thomas S.

    2009-01-01

    Thyrotropin-releasing hormone (TRH) has previously been shown to promote wakefulness and to induce arousal from hibernation. Expression of TRH receptor 1 (TRH-R1) is enriched in the tuberal and lateral hypothalamic area (LHA), brain regions in which the hypocretin/orexin (Hcrt) cells are located. Since the Hcrt system is implicated in sleep/wake control, we hypothesized that TRH provides modulatory input to the Hcrt cells. In vitro electrophysiological studies showed that bath application of TRH caused concentration-dependent membrane depolarization, decreased input resistance, and increased firing rate of identified Hcrt neurons. In the presence of tetrodotoxin, TRH induced inward currents that were associated with a decrease in frequency, but not amplitude, of miniature postsynaptic currents (PSCs). Ion substitution experiments suggested that the TRH-induced inward current was mediated in part by Ca2+ influx. Although TRH did not significantly alter either the frequency or amplitude of spontaneous excitatory PSCs, TRH (100nM) increased the frequency of spontaneous inhibitory PSCs by 2-fold without affecting the amplitude of these events, indicating increased presynaptic GABA release onto Hcrt neurons. In contrast, TRH significantly reduced the frequency, but not amplitude, of miniature excitatory PSCs without affecting miniature inhibitory PSC frequency or amplitude, indicating that TRH also reduces the probability of glutamate release onto Hcrt neurons. When injected into the LHA, TRH increased locomotor activity in wild type mice but not in orexin/ataxin-3 mice in which the Hcrt neurons degenerate postnatally. Together, these results are consistent with the hypothesis that TRH modulates behavioral arousal, in part, through the Hcrt system. PMID:19321767

  2. COX-2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus

    PubMed Central

    Kreiss, C; Birder, L A; Kiss, S; VanBibber, M M; Bauer, A J

    2003-01-01

    Background and aims: Cyclooxygenase 2 (COX-2) and prostaglandins (PGs) participate in the pathogenesis of inflammatory postoperative ileus. We sought to determine whether the emerging neuronal modulator COX-2 plays a significant role in primary afferent activation during postoperative ileus using spinal Fos expression as a marker. Methods: Rats, and COX-2+/+ and COX-2−/− mice underwent simple intestinal manipulation. The effect of intestinal manipulation on Fos immunoreactivity (IR) in the L5-S1 spinal cord, in situ circumference, and postoperative leucocytic infiltrate of the intestinal muscularis was measured. Postoperative PGE2 production was measured in peritoneal lavage fluid. The dependence of these parameters on COX-2 was studied in pharmacological (DFU, Merck- Frosst, selective COX-2 inhibitor) and genetic (COX-2−/− mice) models. Results: Postoperative Fos IR increased 3.7-fold in rats and 2.2-fold in mice. Both muscularis leucocytic infiltrate and the circumference of the muscularis increased significantly in rats and COX-2+/+ mice postoperatively, indicating dilating ileus. Surgical manipulation markedly increased PGE2 levels in the peritoneal cavity. DFU pretreatment and the genetic absence of COX-2−/− prevented dilating ileus, and leucocytic infiltrate was diminished by 40% with DFU and by 54% in COX-2−/− mice. DFU reversed postsurgical intra- abdominal PGE2 levels to normal. Fos IR after intestinal manipulation was attenuated by approximately 50% in DFU treated rats and in COX-2−/− mice. Conclusions: Postoperatively, small bowel manipulation causes a significant and prolonged increase in spinal Fos expression, suggesting prolonged primary afferent activation. COX-2 plays a key role in this response. This activation of primary afferents may subsequently initiate inhibitory motor reflexes to the gut, contributing to postoperative ileus. PMID:12631664

  3. Increasing population, limited dental insurance, but increasing use of services.

    PubMed

    Waldman, H Barry; Truhlar, Mary Rose

    2010-01-01

    During the careers of many current and soon-to-be dental practitioners, one-in-five residents of the U.S. will be 65-plus years of age. Although the current population of seniors has limited dental insurance coverage, older Americans are increasing their use of services. Demographic variations are reviewed in terms of the need for services, dental visit patterns and expenditures for services. A challenge is presented to prepare practitioners for the care of this burgeoning population. PMID:20359067

  4. The Effect of Increasing Mass upon Locomotion

    NASA Technical Reports Server (NTRS)

    DeWitt, John; Hagan, Donald

    2007-01-01

    The purpose of this investigation was to determine if increasing body mass while maintaining bodyweight would affect ground reaction forces and joint kinetics during walking and running. It was hypothesized that performing gait with increased mass while maintaining body weight would result in greater ground reaction forces, and would affect the net joint torques and work at the ankle, knee and hip when compared to gait with normal mass and bodyweight. Vertical ground reaction force was measured for ten subjects (5M/5F) during walking (1.34 m/s) and running (3.13 m/s) on a treadmill. Subjects completed one minute of locomotion at normal mass and bodyweight and at four added mass (AM) conditions (10%, 20%, 30% and 40% of body mass) in random order. Three-dimensional joint position data were collected via videography. Walking and running were analyzed separately. The addition of mass resulted in several effects. Peak impact forces and loading rates increased during walking, but decreased during running. Peak propulsive forces decreased during walking and did not change during running. Stride time increased and hip extensor angular impulse and positive work increased as mass was added for both styles of locomotion. Work increased at a greater rate during running than walking. The adaptations to additional mass that occur during walking are different than during running. Increasing mass during exercise in microgravity may be beneficial to increasing ground reaction forces during walking and strengthening hip musculature during both walking and running. Future study in true microgravity is required to determine if the adaptations found would be similar in a weightless environment.

  5. Fires increase Amazon forest productivity through increases in diffuse radiation