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Sample records for activities includes functions

  1. Effects of restricted feeding on daily fluctuations of hepatic functions including p450 monooxygenase activities in rats.

    PubMed

    Hirao, Jun; Arakawa, Shingo; Watanabe, Kyoko; Ito, Kazumi; Furukawa, Tadashi

    2006-02-10

    Hepatic P450 monooxygenase activities, assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities, show obvious daily fluctuations in male rats with high values during the dark period and low values during the light period. We have already confirmed that the ACD activities are controlled by the suprachiasmatic nucleus (SCN), which is well known as the oscillator of circadian rhythm. Recently, it is reported that circadian oscillators exist not only in the SCN but also in peripheral organs. To date, it is unclear which circadian oscillators predominantly drive the daily fluctuations of hepatic ACD activities. To address this question, we examined the effects of restricted feeding, which uncouples the circadian oscillators in the liver from the central pacemaker in the SCN, on the daily fluctuations in hepatic ACD activities in male rats. Here we show that restricted feeding inverts the oscillation phase of the daily fluctuations in hepatic ACD activities. Regarding the hepatic P450 content, there were no fluctuations between the light and dark periods under ad libitum and restricted feeding conditions. Therefore, it is considered that the daily fluctuations in hepatic ACD activities are predominantly driven by the circadian factors in peripheral organs rather than by the oscillator in the SCN directly.

  2. Preschool Curriculum: A Child Centered Curriculum of Concepts and Activities Including All of the CDA Functional Areas--Bi-lingual and Home Activities.

    ERIC Educational Resources Information Center

    Cunningham, Dorothy, Comp.

    This preschool resource curriculum, intended for use in a Head Start center, was written to correspond with a work plan and curriculum for children 3 to 5 years of age. The units included in the curriculum guide are aimed at integrating growth experiences with the learning of basic skills. Each of the 16 units contains material related to each of…

  3. Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment.

    PubMed

    Kron, Miriam; Howell, C James; Adams, Ian T; Ransbottom, Michael; Christian, Diana; Ogier, Michael; Katz, David M

    2012-10-01

    Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and methyl-CpG-binding protein 2 (Mecp2)-null (Null) mice, a model of RTT, before and after the appearance of overt symptoms (3 and 6 weeks of age, respectively). At 6 weeks, Null mice exhibit significantly less Fos labeling than Wt in limbic cortices and subcortical structures, including key nodes in the default mode network. In contrast, Null mice exhibit significantly more Fos labeling than Wt in the hindbrain, most notably in cardiorespiratory regions of the nucleus tractus solitarius (nTS). Using nTS as a model, whole-cell recordings demonstrated that increased Fos expression in Nulls at 6 weeks of age is associated with synaptic hyperexcitability, including increased frequency of spontaneous and miniature EPSCs and increased amplitude of evoked EPSCs in Nulls. No such effect of genotype on Fos or synaptic function was seen at 3 weeks. In the mutant forebrain, reduced Fos expression, as well as abnormal sensorimotor function, were reversed by the NMDA receptor antagonist ketamine. In light of recent findings that the default mode network is hypoactive in autism, our data raise the possibility that hypofunction within this meta-circuit is a shared feature of RTT and other ASDs and is reversible. PMID:23035095

  4. Protein interaction module-assisted function X (PIMAX) approach to producing challenging proteins including hyperphosphorylated tau and active CDK5/p25 kinase complex.

    PubMed

    Sui, Dexin; Xu, Xinjing; Ye, Xuemei; Liu, Mengyu; Mianecki, Maxwell; Rattanasinchai, Chotirat; Buehl, Christopher; Deng, Xiexiong; Kuo, Min-Hao

    2015-01-01

    Many biomedically critical proteins are underrepresented in proteomics and biochemical studies because of the difficulty of their production in Escherichia coli. These proteins might possess posttranslational modifications vital to their functions, tend to misfold and be partitioned into bacterial inclusion bodies, or act only in a stoichiometric dimeric complex. Successful production of these proteins requires efficient interaction between these proteins and a specific "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a natural physical partner within the dimeric complex. Here we report the design and application of a protein interaction module-assisted function X (PIMAX) system that effectively overcomes these hurdles. By fusing two proteins of interest to a pair of well-studied protein-protein interaction modules, we were able to potentiate the association of these two proteins, resulting in successful production of an enzymatically active cyclin-dependent kinase complex and hyperphosphorylated tau protein, which is intimately linked to Alzheimer disease. Furthermore, using tau isoforms quantitatively phosphorylated by GSK-3β and CDK5 kinases via PIMAX, we demonstrated the hyperphosphorylation-stimulated tau oligomerization in vitro, paving the way for new Alzheimer disease drug discoveries. Vectors for PIMAX can be easily modified to meet the needs of different applications. This approach thus provides a convenient and modular suite with broad implications for proteomics and biomedical research.

  5. Synthesis and Exploratory Catalysis of 3d Metals: Group-Transfer Reactions, and the Activation and Functionalization of Small Molecules Including Greenhouse Gases

    SciTech Connect

    Mindiola, Daniel J.

    2014-05-07

    Our work over the past three years has resulted in the development of electron rich and low-coordinate vanadium fragments, molecular nitrides of vanadium and parent imide systems of titanium, and the synthesis of phosphorus containing molecules of the 3d transition metal series. Likewise, with financial support from BES Division in DOE (DE-FG02-07ER15893), we now completed the full characterization of the first single molecular magnet (SMM) of Fe(III). We demonstrated that this monomeric form of Fe(III) has an unusual slow relaxation of the magnetization under zero applied field. To make matters more interesting, this system also undergoes a rare example of an intermediate to high-spin transition (an S = 3/2 to S = 5/2 transition). In 2010 we reported the synthesis of the first neutral and low-coordinate vanadium complexes having the terminal nitride functionality. We have now completed a full study to understand formation of the nitride ligand from the metastable azide precursor, and have also explored the reactivity of the nitride ligand in the context of incomplete and complete N-atom transfer. During the 2010-2013 period we also discovered a facile approach to assemble low-coordinate and low-valent vanadium(II) complexes and exploit their multielectron chemistry ranging from 1-3 electrons. Consequently, we can now access 3d ligand frameworks such as cyclo-P3 (and its corresponding radical anion), nitride radical anions and cations, low-coordinate vanadium oxo’s, and the first example of a vanadium thionitrosyl complex. A cis-divacant iron(IV) imido having some ligand centered radical has been also discovered, and we are in the process of elucidating its electronic structure (in particular the sign of zero field splitting and the origin of its magnitude), bonding and reactivity. We have also revisited some paramagnetic and classic metallocene compounds with S >1/2 ground states in order to understand their reactivity patterns and electronic structure. Lastly

  6. Toward the standard population synthesis model of the X-ray background: Evolution of X-ray luminosity and absorption functions of active galactic nuclei including Compton-thick populations

    SciTech Connect

    Ueda, Yoshihiro; Akiyama, Masayuki; Hasinger, Günther; Miyaji, Takamitsu; Watson, Michael G.

    2014-05-10

    We present the most up to date X-ray luminosity function (XLF) and absorption function of active galactic nuclei (AGNs) over the redshift range from 0 to 5, utilizing the largest, highly complete sample ever available obtained from surveys performed with Swift/BAT, MAXI, ASCA, XMM-Newton, Chandra, and ROSAT. The combined sample, including that of the Subaru/XMM-Newton Deep Survey, consists of 4039 detections in the soft (0.5-2 keV) and/or hard (>2 keV) band. We utilize a maximum likelihood method to reproduce the count rate versus redshift distribution for each survey, by taking into account the evolution of the absorbed fraction, the contribution from Compton-thick (CTK) AGNs, and broadband spectra of AGNs, including reflection components from tori based on the luminosity- and redshift-dependent unified scheme. We find that the shape of the XLF at z ∼ 1-3 is significantly different from that in the local universe, for which the luminosity-dependent density evolution model gives much better description than the luminosity and density evolution model. These results establish the standard population synthesis model of the X-ray background (XRB), which well reproduces the source counts, the observed fractions of CTK AGNs, and the spectrum of the hard XRB. The number ratio of CTK AGNs to the absorbed Compton-thin (CTN) AGNs is constrained to be ≈0.5-1.6 to produce the 20-50 keV XRB intensity within present uncertainties, by assuming that they follow the same evolution as CTN AGNs. The growth history of supermassive black holes is discussed based on the new AGN bolometric luminosity function.

  7. Everglades National Park Including Biscayne National Park. Activity Book.

    ERIC Educational Resources Information Center

    Ruehrwein, Dick

    Intended to help elementary school children learn about the resources of the Everglades and Biscayne National Parks, this activity book includes information, puzzles, games, and quizzes. The booklet deals with concepts related to: (1) the seasons; (2) fire ecology; (3) water; (4) fish; (5) mammals; (6) mosquitos; (7) birds; (8) venomous snakes;…

  8. A scattering function of star polymers including excluded volume effects

    DOE PAGES

    Li, Xin; Do, Changwoo; Liu, Yun; Sánchez-Diáz, Luis; Smith, Gregory; Chen, Wei-Ren

    2014-11-04

    In this work we present a new model for the form factor of a star polymer consisting of self-avoiding branches. This new model incorporates excluded volume effects and is derived from the two point correlation function for a star polymer.. We compare this model to small angle neutron scattering (SANS) measurements from polystyrene (PS) stars immersed in a good solvent, tetrahydrofuran (THF). It is shown that this model provides a good description of the scattering signature originating from the excluded volume effect and it explicitly elucidates the connection between the global conformation of a star polymer and the local stiffnessmore » of its constituent branch.« less

  9. A scattering function of star polymers including excluded volume effects

    SciTech Connect

    Li, Xin; Do, Changwoo; Liu, Yun; Sánchez-Diáz, Luis; Smith, Gregory; Chen, Wei-Ren

    2014-11-04

    In this work we present a new model for the form factor of a star polymer consisting of self-avoiding branches. This new model incorporates excluded volume effects and is derived from the two point correlation function for a star polymer.. We compare this model to small angle neutron scattering (SANS) measurements from polystyrene (PS) stars immersed in a good solvent, tetrahydrofuran (THF). It is shown that this model provides a good description of the scattering signature originating from the excluded volume effect and it explicitly elucidates the connection between the global conformation of a star polymer and the local stiffness of its constituent branch.

  10. Valuing preferences over stormwater management outcomes including improved hydrologic function

    NASA Astrophysics Data System (ADS)

    LondoñO Cadavid, Catalina; Ando, Amy W.

    2013-07-01

    Stormwater runoff causes environmental problems such as flooding, soil erosion, and water pollution. Conventional stormwater management has focused primarily on flood reduction, while a new generation of decentralized stormwater solutions yields ancillary benefits such as healthier aquatic habitat, improved surface water quality, and increased water table recharge. Previous research has estimated values for flood reduction from stormwater management, but no estimates exist for the willingness to pay (WTP) for some of the other environmental benefits of alternative approaches to stormwater control. This paper uses a choice experiment survey of households in Champaign-Urbana, Illinois, to estimate the values of several attributes of stormwater management outcomes. We analyzed data from 131 surveyed households in randomly selected neighborhoods. We find that people value reduced basement flooding more than reductions in yard or street flooding, but WTP for basement flood reduction in the area only exists if individuals are currently experiencing significant flooding themselves. Citizens value both improved water quality and improved hydrologic function and aquatic habitat from runoff reduction. Thus, widespread investment in low impact development stormwater solutions could have very large total benefits, and stormwater managers should be wary of policies and infrastructure plans that reduce flooding at the expense of water quality and aquatic habitat.

  11. Antiradical activity of gallic acid included in lipid interphases.

    PubMed

    Salcedo, C L; Frías, M A; Cutro, A C; Nazareno, M A; Disalvo, E A

    2014-10-01

    Polyphenols are well known as antioxidant agents and by their effects on the hydration layers of lipid interphases. Among them, gallic acid and its derivatives are able to decrease the dipole potential and to act in water as a strong antioxidant. In this work we have studied both effects on lipid interphases in monolayers and bilayers of dimyristoylphosphatidylcholine. The results show that gallic acid (GA) increases the negative surface charges of large unilamellar vesicles (LUVs) and decreases the dipole potential of the lipid interphase. As a result, positively charged radical species such as ABTS(+) are able to penetrate the membrane forming an association with GA. These results allow discussing the antiradical activity (ARA) of GA at the membrane phase which may be taking place in water spaces between the lipids.

  12. A cerebrovascular response model for functional neuroimaging including dynamic cerebral autoregulation

    PubMed Central

    Diamond, Solomon Gilbert; Perdue, Katherine L.; Boas, David A.

    2009-01-01

    Functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) can be used to isolate an evoked response to a stimulus from significant background physiological fluctuations. Data analysis approaches typically use averaging or linear regression to remove this physiological baseline with varying degrees of success. Biophysical model-based analysis of the functional hemodynamic response has also been advanced previously with the Balloon and Windkessel models. In the present work, a biophysical model of systemic and cerebral circulation and gas exchange is applied to resting state NIRS neuroimaging data from 10 human subjects. The model further includes dynamic cerebral autoregulation, which modulates the cerebral arteriole compliance to control cerebral blood flow. This biophysical model allows for prediction, from noninvasive blood pressure measurements, of the background hemodynamic fluctuations in the systemic and cerebral circulations. Significantly higher correlations with the NIRS data were found using the biophysical model predictions compared to blood pressure regression and compared to transfer function analysis (multifactor ANOVA, p<0.0001). This finding supports the further development and use of biophysical models for removing baseline activity in functional neuroimaging analysis. Future extensions of this work could model changes in cerebrovascular physiology that occur during development, aging and disease. PMID:19442671

  13. Rabbit-Specific Ventricular Model of Cardiac Electrophysiological Function including Specialized Conduction System

    PubMed Central

    Bordas, R.; Gillow, K.; Lou, Q.; Efimov, I. R.; Gavaghan, D.; Kohl, P.; Grau, V.; Rodriguez, B.

    2011-01-01

    The function of the ventricular specialized conduction system in the heart is to ensure the coordinated electrical activation of the ventricles. It is therefore critical to the overall function of the heart, and has also been implicated as an important player in various diseases, including lethal ventricular arrhythmias such as ventricular fibrillation and drug-induced torsades de pointes. However, current ventricular models of electrophysiology usually ignore, or include highly simplified representations of the specialized conduction system. Here, we describe the development of a image-based, species-consistent, anatomically-detailed model of rabbit ventricular electrophysiology that incorporates a detailed description of the free-running part of the specialized conduction system. Techniques used for the construction of the geometrical model of the specialized conduction system from a magnetic resonance dataset and integration of the system model into a ventricular anatomical model, developed from the same dataset, are described. Computer simulations of rabbit ventricular electrophysiology are conducted using the novel anatomical model and rabbit-specific membrane kinetics to investigate the importance of the components and properties of the conduction system in determining ventricular function under physiological conditions. Simulation results are compared to panoramic optical mapping experiments for model validation and results interpretation. Full access is provided to the anatomical models developed in this study. PMID:21672547

  14. Comprehensive functional characterization of murine infantile Batten disease including Parkinson-like behavior and dopaminergic markers.

    PubMed

    Dearborn, Joshua T; Harmon, Steven K; Fowler, Stephen C; O'Malley, Karen L; Taylor, George T; Sands, Mark S; Wozniak, David F

    2015-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten disease) is a neurodegenerative lysosomal storage disease caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). The PPT1-deficient mouse (Cln1(-/-)) is a useful phenocopy of human INCL. Cln1(-/-) mice display retinal dysfunction, seizures, motor deficits, and die at ~8 months of age. However, little is known about the cognitive and behavioral functions of Cln1(-/-) mice during disease progression. In the present study, younger (~1-2 months of age) Cln1(-/-) mice showed minor deficits in motor/sensorimotor functions while older (~5-6 months of age) Cln1(-/-) mice exhibited more severe impairments, including decreased locomotor activity, inferior cued water maze performance, decreased running wheel ability, and altered auditory cue conditioning. Unexpectedly, certain cognitive functions such as some learning and memory capabilities seemed intact in older Cln1(-/-) mice. Younger and older Cln1(-/-) mice presented with walking initiation defects, gait abnormalities, and slowed movements, which are analogous to some symptoms reported in INCL and parkinsonism. However, there was no evidence of alterations in dopaminergic markers in Cln1(-/-) mice. Results from this study demonstrate quantifiable changes in behavioral functions during progression of murine INCL and suggest that Parkinson-like motor/sensorimotor deficits in Cln1(-/-) mice are not mediated by dopamine deficiency. PMID:26238334

  15. Optimal design of active and semi-active suspensions including time delays and preview

    NASA Astrophysics Data System (ADS)

    Hac', A.; Youn, I.

    1993-10-01

    Several control laws for active and semi-active suspension based on a linear half car model are derived and investigated. The strategies proposed take full advantage of the fact that the road input to the rear wheels is a delayed version of that to the front wheels, which in turn can be obtained either from the measurements of the front wheels and body motions or by direct preview of road irregularities if preview sensors are available. The suspension systems are optimized with respect to ride comfort, road holding and suspension rattle space as expressed by the mean-square-values of body acceleration (including effects of heave and pitch), tire deflections and front and rear suspension travels. The optimal control laws that minimize the given performance index and include passivity constraints in the semi-active case are derived using calculus of variation. The optimal semi-active suspension becomes piecewise linear, varying between passive and fully active systems and combinations of them. The performances of active and semi-active systems with and without preview were evaluated by numerical simulation in the time and frequency domains. The results show that incorporation of time delay between the front and rear axles in controller design improves the dynamic behavior of the rear axle and control of body pitch motion, while additional preview improves front wheel dynamics and body heave.

  16. Obstacles to activity pacing: assessment, relationship to activity and functioning.

    PubMed

    Cane, Douglas; McCarthy, Mary; Mazmanian, Dwight

    2016-07-01

    Activity pacing is frequently included among the strategies provided to individuals with chronic pain to manage pain and improve functioning. Individuals with chronic pain may, however, limit their use of activity pacing because they perceive significant obstacles to its use. This study describes the development of a measure to assess obstacles to activity pacing and examines the relationship of this measure to activity patterns and functioning. A sample of 637 individuals with chronic pain completed items describing potential obstacles to activity pacing as part of their pretreatment assessment. Item analyses were used to construct a 14-item measure of obstacles to activity pacing. A subset of these individuals completed the measure again after completion of a group treatment program. The resulting measure demonstrated excellent internal consistency and was minimally affected by social desirability. Correlations with measures of activity and psychosocial functioning provided initial construct validity for the measure. Sex differences were found with women initially identifying more obstacles to activity pacing. Fewer obstacles were identified by both men and women after treatment, and these changes were related to modest changes in activity patterns and functioning. The present results identify a number of obstacles that may limit the use of activity pacing by individuals with chronic pain. Treatment may result in a decrease in the number of obstacles identified, and this change is related to changes in the individual's activity pattern and psychosocial functioning. PMID:26963845

  17. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  18. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    PubMed Central

    Ferreira, Naomi Vidal; Cunha, Paulo Jannuzzi; da Costa, Danielle Irigoyen; dos Santos, Fernando; Costa, Fernando Oliveira; Consolim-Colombo, Fernanda; Irigoyen, Maria Cláudia

    2015-01-01

    Introduction Peripheral arterial disease, as measured by the ankle–brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. Aim To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. Method The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). Results Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. Conclusion This study found an independent association between

  19. Functionalized active-nucleus complex sensor

    DOEpatents

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  20. Deep Neural Networks with Multistate Activation Functions

    PubMed Central

    Cai, Chenghao; Xu, Yanyan; Ke, Dengfeng; Su, Kaile

    2015-01-01

    We propose multistate activation functions (MSAFs) for deep neural networks (DNNs). These MSAFs are new kinds of activation functions which are capable of representing more than two states, including the N-order MSAFs and the symmetrical MSAF. DNNs with these MSAFs can be trained via conventional Stochastic Gradient Descent (SGD) as well as mean-normalised SGD. We also discuss how these MSAFs perform when used to resolve classification problems. Experimental results on the TIMIT corpus reveal that, on speech recognition tasks, DNNs with MSAFs perform better than the conventional DNNs, getting a relative improvement of 5.60% on phoneme error rates. Further experiments also reveal that mean-normalised SGD facilitates the training processes of DNNs with MSAFs, especially when being with large training sets. The models can also be directly trained without pretraining when the training set is sufficiently large, which results in a considerable relative improvement of 5.82% on word error rates. PMID:26448739

  1. Molecular density functional theory of water including density-polarization coupling

    NASA Astrophysics Data System (ADS)

    Jeanmairet, Guillaume; Levy, Nicolas; Levesque, Maximilien; Borgis, Daniel

    2016-06-01

    We present a three-dimensional molecular density functional theory of water derived from first-principles that relies on the particle’s density and multipolar polarization density and includes the density-polarization coupling. This brings two main benefits: (i) scalar density and vectorial multipolar polarization density fields are much more tractable and give more physical insight than the full position and orientation densities, and (ii) it includes the full density-polarization coupling of water, that is known to be non-vanishing but has never been taken into account. Furthermore, the theory requires only the partial charge distribution of a water molecule and three measurable bulk properties, namely the structure factor and the Fourier components of the longitudinal and transverse dielectric susceptibilities.

  2. Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family That Includes Sphingomyelinase D in Sicariid Spider Venoms

    PubMed Central

    Bodner, Melissa R.; Cordes, Matthew H.J.; Baldwin, Katherine L.; Rynerson, Melody R.; Burns, Scott N.; Zobel-Thropp, Pamela A.

    2009-01-01

    The venom enzyme sphingomyelinase D (SMase D) in the spider family Sicariidae (brown or fiddleback spiders [Loxosceles] and six-eyed sand spiders [Sicarius]) causes dermonecrosis in mammals. SMase D is in a gene family with multiple venom-expressed members that vary in functional specificity. We analyze molecular evolution of this family and variation in SMase D activity among crude venoms using a data set that represents the phylogenetic breadth of Loxosceles and Sicarius. We isolated a total of 190 nonredundant nucleotide sequences encoding 168 nonredundant amino acid sequences of SMase D homologs from 21 species. Bayesian phylogenies support two major clades that we name α and β, within which we define seven and three subclades, respectively. Sequences in the α clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have SMase D and dermonecrotic activity. The β clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Gene duplications are frequent, consistent with a birth-and-death model, and there is evidence of purifying selection with episodic positive directional selection. Despite having venom-expressed SMase D homologs, venoms from New World Sicarius have reduced, or no, detectable SMase D activity, and Loxosceles in the Southern African spinulosa group have low SMase D activity. Sequence conservation mapping shows >98% conservation of proposed catalytic residues of the active site and around a plug motif at the opposite end of the TIM barrel, but α and β clades differ in conservation of key residues surrounding the apparent substrate binding pocket. Based on these combined results, we propose an inclusive nomenclature for the gene family, renaming it SicTox, and discuss emerging patterns of functional diversification. PMID:19042943

  3. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... Requirements § 641.864 What functions and activities constitute programmatic activity costs? Programmatic activity costs include, but are not limited to, the costs of the following functions: (a) Participant...

  4. Improvements to the FATOLA computer program including added actively controlled landing gear subroutines

    NASA Technical Reports Server (NTRS)

    Mall, G. H.

    1983-01-01

    Modifications to a multi-degree-of-freedom flexible aircraft take-off and landing analysis (FATOLA) computer program, including a provision for actively controlled landing gears to expand the programs simulation capabilities, are presented. Supplemental instructions for preparation of data and for use of the modified program are included.

  5. Communication: importance sampling including path correlation in semiclassical initial value representation calculations for time correlation functions.

    PubMed

    Pan, Feng; Tao, Guohua

    2013-03-01

    Full semiclassical (SC) initial value representation (IVR) for time correlation functions involves a double phase space average over a set of two phase points, each of which evolves along a classical path. Conventionally, the two initial phase points are sampled independently for all degrees of freedom (DOF) in the Monte Carlo procedure. Here, we present an efficient importance sampling scheme by including the path correlation between the two initial phase points for the bath DOF, which greatly improves the performance of the SC-IVR calculations for large molecular systems. Satisfactory convergence in the study of quantum coherence in vibrational relaxation has been achieved for a benchmark system-bath model with up to 21 DOF.

  6. Operational Dataset Update Functionality Included in the NCAR Research Data Archive Management System

    NASA Astrophysics Data System (ADS)

    Ji, Z.; Worley, S. J.; Schuster, D. C.

    2011-12-01

    Growing complexity, volume, and reliance on operationally created datasets poses challenges to the centers tasked with archiving and curating this information. Past tools focused on data delivered via media, such as tape, or data downloaded by single dataset customized ftp scripting. Presently nearly all data are acquired via network interactions, which can happen many times per day. Prior archive management technologies do not scale to this new paradigm. The Research Data Archive Management System (RDAMS) was developed to meet this challenge and has been implemented to support archive management within the Research Data Archive (RDA) at the National Center for Atmospheric Research (NCAR). RDAMS is driven by open source based databases and utilities, and is designed to support the complete data archive cycle by fetching, interrogating, archiving, and providing long-term research data stewardship. A good example of RDAMS functionality is found in the utility developed to specifically manage operational dataset updates, and can be applied to any dataset that requires periodic updating. The RDAMS dataset update utility (DSUPDT) accomplishes four basic tasks: 1) contact and query a remote server to see if new or modified data are available, 2) move data from a remote host to a local system and verify data transfer integrity, 3) execute any required data processing steps including metadata harvesting, 4) archive data to local disk and backup media systems. To accomplish these tasks across a diverse variety of datasets, DSUPDT incorporates a broad base of functionality. For example, it can be configured to run according to many different data set requirements, handles multiple web protocols, automatically recovers from system outages at the remote or local site, can execute 3rd party data manipulation software, and accommodates irregular data delivery schedules. Currently over 150 RDA dataset products are configured to be under DSUPDT control, with datasets being updated

  7. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice

    PubMed Central

    Weisberg, S; Leibel, R; Tortoriello, D V

    2016-01-01

    Background: Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background). Results: In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity. Conclusions: These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance. PMID:27110686

  8. Functional Stability of Plasminogen Activator Inhibitor-1

    PubMed Central

    Kuru, Pinar; Toksoy Oner, Ebru; Agirbasli, Mehmet

    2014-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease. PMID:25386620

  9. Pulmonary Function after Treatment for Embryonal Brain Tumors on SJMB03 that Included Craniospinal Irradiation

    PubMed Central

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose Treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods Protocol XXXXX enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by spirometry, total lung capacity (TLC) by nitrogen washout or plethysmography and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOcorr)] were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after completion of treatment (ACT) were compared using exact Wilcoxon signed rank tests and repeated measures models. Results 303 eligible patients (spine dose: ≤ 2345 cGy- 201; > 2345 cGy-102; proton beam, 20) were enrolled between June 24, 2003 and March 1, 2010, 260 of whom had at least one PFT. The median age at diagnosis was 8.9 years (range, 3.1–20.4 years). The median thoracic spinal RT dose was 23.4 Gy (Inter Quartile Range (IQR), 23.4–36.0 Gy). The median cyclophosphamide dose was 16.0 g/m2 (IQR, 15.7–16.0 g/m2). 24 and 60 months ACT, DLCOcorr was <75% predicted in 23% (27/118) and 25% (21/84), FEV1 <80% predicted in 20% (34/170) and 29% (32/109), FVC < 80% predicted in 27% (46/172) and 28% (30/108) and TLC <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCOcorr was significantly decreased 24 (median difference (MD) in % predicted, − 3.00%; p=0.028) and 60 months ACT (MD in % predicted, − 6.00%; p=0.033) compared to the end of RT. These significant decreases in DLCOcorr were also observed in repeated measures models (p=0.011 and p=0.032 at 24 and 60 months ACT, respectively). Conclusions A significant minority of EBT survivors experience PFT deficits following CSI. Continued monitoring of this cohort is planned. PMID:26279023

  10. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    SciTech Connect

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  11. Nonseparable exchange-correlation functional for molecules, including homogeneous catalysis involving transition metals.

    PubMed

    Yu, Haoyu S; Zhang, Wenjing; Verma, Pragya; He, Xiao; Truhlar, Donald G

    2015-05-14

    The goal of this work is to develop a gradient approximation to the exchange-correlation functional of Kohn-Sham density functional theory for treating molecular problems with a special emphasis on the prediction of quantities important for homogeneous catalysis and other molecular energetics. Our training and validation of exchange-correlation functionals is organized in terms of databases and subdatabases. The key properties required for homogeneous catalysis are main group bond energies (database MGBE137), transition metal bond energies (database TMBE32), reaction barrier heights (database BH76), and molecular structures (database MS10). We also consider 26 other databases, most of which are subdatabases of a newly extended broad database called Database 2015, which is presented in the present article and in its ESI. Based on the mathematical form of a nonseparable gradient approximation (NGA), as first employed in the N12 functional, we design a new functional by using Database 2015 and by adding smoothness constraints to the optimization of the functional. The resulting functional is called the gradient approximation for molecules, or GAM. The GAM functional gives better results for MGBE137, TMBE32, and BH76 than any available generalized gradient approximation (GGA) or than N12. The GAM functional also gives reasonable results for MS10 with an MUE of 0.018 Å. The GAM functional provides good results both within the training sets and outside the training sets. The convergence tests and the smooth curves of exchange-correlation enhancement factor as a function of the reduced density gradient show that the GAM functional is a smooth functional that should not lead to extra expense or instability in optimizations. NGAs, like GGAs, have the advantage over meta-GGAs and hybrid GGAs of respectively smaller grid-size requirements for integrations and lower costs for extended systems. These computational advantages combined with the relatively high accuracy for all

  12. Population and Human Development: A Course Curriculum Including Lesson Plans, Activities, and Bibliography. Revised.

    ERIC Educational Resources Information Center

    Murphy, Elaine M.; Long, Alison T.

    This course outline suggests materials and learning activities on the interrelated causes and consequences of population growth and other population matters. The document describes 15 class sessions which integrate information for sociology, anthropology, psychology, biology, animal behavior, and education. Topics include the history of human…

  13. 76 FR 10385 - Agency Information Collection Activities: Various Contract Related Forms That Will be Included in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... SECURITY Agency Information Collection Activities: Various Contract Related Forms That Will be Included in the Homeland Security Acquisition Regulation, DHS FORM 0700-01, DHS FORM 0700-02, DHS FORM 0700-03...: The Department of Homeland Security, Office of Chief Procurement Officer, Acquisition Policy...

  14. Comprehensive mathematical simulation of functional magnetic resonance imaging time series including motion-related image distortion and spin saturation effect.

    PubMed

    Kim, Boklye; Yeo, Desmond T B; Bhagalia, Roshni

    2008-02-01

    There has been vast interest in determining the feasibility of functional magnetic resonance imaging (fMRI) as an accurate method of imaging brain function for patient evaluations. The assessment of fMRI as an accurate tool for activation localization largely depends on the software used to process the time series data. The performance evaluation of different analysis tools is not reliable unless truths in motion and activation are known. Lack of valid truths has been the limiting factor for comparisons of different algorithms. Until now, currently available phantom data do not include comprehensive accounts of head motion. While most fMRI studies assume no interslice motion during the time series acquisition in fMRI data acquired using a multislice and single-shot echo-planar imaging sequence, each slice is subject to a different set of motion parameters. In this study, in addition to known three-dimensional motion parameters applied to each slice, included in the time series computation are geometric distortion from field inhomogeneity and spin saturation effect as a result of out-of-plane head motion. We investigated the effect of these head motion-related artifacts and present a validation of the mapping slice-to-volume (MSV) algorithm for motion correction and activation detection against the known truths. MSV was evaluated, and showed better performance in comparison with other widely used fMRI data processing software, which corrects for head motion with a volume-to-volume realignment method. Furthermore, improvement in signal detection was observed with the implementation of the geometric distortion correction and spin saturation effect compensation features in MSV. PMID:17662548

  15. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for... Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. (a) Agents....

  16. Classical density-functional theory of inhomogeneous water including explicit molecular structure and nonlinear dielectric response.

    PubMed

    Lischner, Johannes; Arias, T A

    2010-02-11

    We present an accurate free-energy functional for liquid water written in terms of a set of effective potential fields in which fictitious noninteracting water molecules move. The functional contains an exact expression of the entropy of noninteracting molecules and thus provides an ideal starting point for the inclusion of complex intermolecular interactions which depend on the orientation of the interacting molecules. We show how an excess free-energy functional can be constructed to reproduce the following properties of water: the dielectric response; the experimental site-site correlation functions; the surface tension; the bulk modulus of the liquid and the variation of this modulus with pressure; the density of the liquid and the vapor phase; and liquid-vapor coexistence. As a demonstration, we present results for the application of this theory to the behavior of liquid water in a parallel plate capacitor. In particular, we make predictions for the dielectric response of water in the nonlinear regime, finding excellent agreement with known data.

  17. Active seat suspension for a small vehicle: considerations for control system including observer

    NASA Astrophysics Data System (ADS)

    Katsumata, Hiroyuki; Shiino, Hiroshi; Oshinoya, Yasuo; Ishibashi, Kazuhisa; Ozaki, Koichi; Ogino, Hirohiko

    2007-12-01

    We have examined the improvement of ride quality and the reduction of riding fatigue brought about by the active control of the seat suspension of small vehicles such as one-seater electric automobiles. A small active seat suspension, which is easy to install, was designed and manufactured for one-seater electric automobiles. For the actuator, a maintenance-free voice coil motor used as a direct drive was adopted. For fundamental considerations, we designed a one-degree-of-freedom model for the active seat suspension system. Then, we designed a disturbance cancellation control system that includes the observer for a two-degree-of-freedom model. In an actual driving test, a test road, in which the concavity and convexity of an actual road surface were simulated using hard rubber, was prepared and the control performance of vertical vibrations of the seat surface during driving was examined. As a result, in comparison with the one-degree-of-freedom control system, it was confirmed that the control performance was improved by the two-degree-of-freedom control system that includes the observer.

  18. Dynamical Density Functional Theory for Orientable Colloids Including Inertia and Hydrodynamic Interactions

    NASA Astrophysics Data System (ADS)

    Durán-Olivencia, Miguel A.; Goddard, Benjamin D.; Kalliadasis, Serafim

    2016-08-01

    Over the last few decades, classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become powerful tools in the study of colloidal fluids. Recently, previous DDFTs for spherically-symmetric particles have been generalised to take into account both inertia and hydrodynamic interactions, two effects which strongly influence non-equilibrium properties. The present work further generalises this framework to systems of anisotropic particles. Starting from the Liouville equation and utilising Zwanzig's projection-operator techniques, we derive the kinetic equation for the Brownian particle distribution function, and by averaging over all but one particle, a DDFT equation is obtained. Whilst this equation has some similarities with DDFTs for spherically-symmetric colloids, it involves a translational-rotational coupling which affects the diffusivity of the (asymmetric) particles. We further show that, in the overdamped (high friction) limit, the DDFT is considerably simplified and is in agreement with a previous DDFT for colloids with arbitrary-shape particles.

  19. Density functional method including weak interactions: Dispersion coefficients based on the local response approximation

    NASA Astrophysics Data System (ADS)

    Sato, Takeshi; Nakai, Hiromi

    2009-12-01

    A new method to calculate the atom-atom dispersion coefficients in a molecule is proposed for the use in density functional theory with dispersion (DFT-D) correction. The method is based on the local response approximation due to Dobson and Dinte [Phys. Rev. Lett. 76, 1780 (1996)], with modified dielectric model recently proposed by Vydrov and van Voorhis [J. Chem. Phys. 130, 104105 (2009)]. The local response model is used to calculate the distributed multipole polarizabilities of atoms in a molecule, from which the dispersion coefficients are obtained by an explicit frequency integral of the Casimir-Polder type. Thus obtained atomic polarizabilities are also used in the damping function for the short-range singularity. Unlike empirical DFT-D methods, the local response dispersion (LRD) method is able to calculate the dispersion energy from the ground-state electron density only. It is applicable to any geometry, free from physical constants such as van der Waals radii or atomic polarizabilities, and computationally very efficient. The LRD method combined with the long-range corrected DFT functional (LC-BOP) is applied to calculations of S22 weakly bound complex set [Phys. Chem. Chem. Phys. 8, 1985 (2006)]. Binding energies obtained by the LC-BOP + LRD agree remarkably well with ab initio references.

  20. Enzymatically active 2',5'-oligoadenylate synthetases are widely distributed among Metazoa, including protostome lineage.

    PubMed

    Päri, Mailis; Kuusksalu, Anne; Lopp, Annika; Kjaer, Karina Hansen; Justesen, Just; Kelve, Merike

    2014-02-01

    2',5'-Oligoadenylate synthetases (OASs) belong to the nucleotidyl transferase family together with poly(A) polymerases, CCA-adding enzymes and the recently discovered cyclic-GMP-AMP synthase (cGAS). Mammalian OASs have been thoroughly characterized as components of the interferon-induced antiviral system. The OAS activity and the respective genes were also discovered in marine sponges where the interferon system is absent. In this study the recombinant OASs from several multicellular animals and their closest unicellular relative, a choanoflagellate, were expressed in a bacterial expression system and their enzymatic activities were examined. We demonstrated 2-5A synthesizing activities of OASs from the marine sponge Tedania ignis, a representative of the phylogenetically oldest metazoan phylum (Porifera), from an invertebrate of the protostome lineage, the mollusk Mytilus californianus (Mollusca), and from a vertebrate species, a cartilaginous fish Leucoraja erinacea (Chordata). However, the expressed proteins from an amphibian, the salamander Ambystoma mexicanum (Chordata), and from a protozoan, the marine choanoflagellate Monosiga brevicollis (Choanozoa), did not show 2-5A synthesizing activity. Differently from other studied OASs, OAS from the marine sponge T. ignis was able to catalyze the formation of oligomers having both 2',5'- and 3',5'-phosphodiester linkages. Our data suggest that OASs from sponges and evolutionarily higher animals have similar activation mechanisms which still include different affinities and possibly different structural requirements for the activating RNAs. Considering their 2'- and 3'-specificities, sponge OASs could represent a link between evolutionarily earlier nucleotidyl transferases and 2'-specific OASs from higher animals.

  1. Enzymatically active 2',5'-oligoadenylate synthetases are widely distributed among Metazoa, including protostome lineage.

    PubMed

    Päri, Mailis; Kuusksalu, Anne; Lopp, Annika; Kjaer, Karina Hansen; Justesen, Just; Kelve, Merike

    2014-02-01

    2',5'-Oligoadenylate synthetases (OASs) belong to the nucleotidyl transferase family together with poly(A) polymerases, CCA-adding enzymes and the recently discovered cyclic-GMP-AMP synthase (cGAS). Mammalian OASs have been thoroughly characterized as components of the interferon-induced antiviral system. The OAS activity and the respective genes were also discovered in marine sponges where the interferon system is absent. In this study the recombinant OASs from several multicellular animals and their closest unicellular relative, a choanoflagellate, were expressed in a bacterial expression system and their enzymatic activities were examined. We demonstrated 2-5A synthesizing activities of OASs from the marine sponge Tedania ignis, a representative of the phylogenetically oldest metazoan phylum (Porifera), from an invertebrate of the protostome lineage, the mollusk Mytilus californianus (Mollusca), and from a vertebrate species, a cartilaginous fish Leucoraja erinacea (Chordata). However, the expressed proteins from an amphibian, the salamander Ambystoma mexicanum (Chordata), and from a protozoan, the marine choanoflagellate Monosiga brevicollis (Choanozoa), did not show 2-5A synthesizing activity. Differently from other studied OASs, OAS from the marine sponge T. ignis was able to catalyze the formation of oligomers having both 2',5'- and 3',5'-phosphodiester linkages. Our data suggest that OASs from sponges and evolutionarily higher animals have similar activation mechanisms which still include different affinities and possibly different structural requirements for the activating RNAs. Considering their 2'- and 3'-specificities, sponge OASs could represent a link between evolutionarily earlier nucleotidyl transferases and 2'-specific OASs from higher animals. PMID:24184688

  2. Plants as sources of airborne bacteria, including ice nucleation-active bacteria.

    PubMed

    Lindemann, J; Constantinidou, H A; Barchet, W R; Upper, C D

    1982-11-01

    Vertical wind shear and concentration gradients of viable, airborne bacteria were used to calculate the upward flux of viable cells above bare soil and canopies of several crops. Concentrations at soil or canopy height varied from 46 colony-forming units per m over young corn and wet soil to 663 colony-forming units per m over dry soil and 6,500 colony-forming units per m over a closed wheat canopy. In simultaneous samples, concentrations of viable bacteria in the air 10 m inside an alfalfa field were fourfold higher than those over a field with dry, bare soil immediately upwind. The upward flux of viable bacteria over alfalfa was three- to fourfold greater than over dry soil. Concentrations of ice nucleation-active bacteria were higher over plants than over soil. Thus, plant canopies may constitute a major source of bacteria, including ice nucleation-active bacteria, in the air.

  3. Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9.

    PubMed

    Koo, Taeyoung; Lee, Jungjoon; Kim, Jin-Soo

    2015-06-01

    Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.

  4. Accurate description of van der Waals complexes by density functional theory including empirical corrections.

    PubMed

    Grimme, Stefan

    2004-09-01

    An empirical method to account for van der Waals interactions in practical calculations with the density functional theory (termed DFT-D) is tested for a wide variety of molecular complexes. As in previous schemes, the dispersive energy is described by damped interatomic potentials of the form C6R(-6). The use of pure, gradient-corrected density functionals (BLYP and PBE), together with the resolution-of-the-identity (RI) approximation for the Coulomb operator, allows very efficient computations for large systems. Opposed to previous work, extended AO basis sets of polarized TZV or QZV quality are employed, which reduces the basis set superposition error to a negligible extend. By using a global scaling factor for the atomic C6 coefficients, the functional dependence of the results could be strongly reduced. The "double counting" of correlation effects for strongly bound complexes is found to be insignificant if steep damping functions are employed. The method is applied to a total of 29 complexes of atoms and small molecules (Ne, CH4, NH3, H2O, CH3F, N2, F2, formic acid, ethene, and ethine) with each other and with benzene, to benzene, naphthalene, pyrene, and coronene dimers, the naphthalene trimer, coronene. H2O and four H-bonded and stacked DNA base pairs (AT and GC). In almost all cases, very good agreement with reliable theoretical or experimental results for binding energies and intermolecular distances is obtained. For stacked aromatic systems and the important base pairs, the DFT-D-BLYP model seems to be even superior to standard MP2 treatments that systematically overbind. The good results obtained suggest the approach as a practical tool to describe the properties of many important van der Waals systems in chemistry. Furthermore, the DFT-D data may either be used to calibrate much simpler (e.g., force-field) potentials or the optimized structures can be used as input for more accurate ab initio calculations of the interaction energies.

  5. Dynamical density functional theory for arbitrary-shape colloidal fluids including inertia and hydrodynamic interactions

    NASA Astrophysics Data System (ADS)

    Duran-Olivencia, Miguel A.; Goddard, Ben; Kalliadasis, Serafim

    2015-11-01

    Over the last few decades the classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become a remarkably powerful tool in the study of colloidal fluids. Recently there has been extensive research to generalise all previous DDFTs finally yielding a general DDFT equation (for spherical particles) which takes into account both inertia and hydrodynamic interactions (HI) which strongly influence non-equilibrium properties. The present work will be devoted to a further generalisation of such a framework to systems of anisotropic particles. To this end, the kinetic equation for the Brownian particle distribution function is derived starting from the Liouville equation and making use of Zwanzig's projection-operator techniques. By averaging over all but one particle, a DDFT equation is finally obtained with some similarities to that for spherical colloids. However, there is now an inevitable translational-rotational coupling which affects the diffusivity of asymmetric particles. Lastly, in the overdamped (high friction) limit the theory is notably simplified leading to a DDFT equation which agrees with previous derivations. We acknowledge financial support from European Research Council via Advanced Grant No. 247031.

  6. An improved global analysis of nuclear parton distribution functions including RHIC data

    NASA Astrophysics Data System (ADS)

    Eskola, Kari J.; Paukkunen, Hannu; Salgado, Carlos A.

    2008-07-01

    We present an improved leading-order global DGLAP analysis of nuclear parton distribution functions (nPDFs), supplementing the traditionally used data from deep inelastic lepton-nucleus scattering and Drell-Yan dilepton production in proton-nucleus collisions, with inclusive high-pT hadron production data measured at RHIC in d+Au collisions. With the help of an extended definition of the χ2 function, we now can more efficiently exploit the constraints the different data sets offer, for gluon shadowing in particular, and account for the overall data normalization uncertainties during the automated χ2 minimization. The very good simultaneous fit to the nuclear hard process data used demonstrates the feasibility of a universal set of nPDFs, but also limitations become visible. The high-pT forward-rapidity hadron data of BRAHMS add a new crucial constraint into the analysis by offering a direct probe for the nuclear gluon distributions—a sector in the nPDFs which has traditionally been very badly constrained. We obtain a strikingly stronger gluon shadowing than what has been estimated in previous global analyses. The obtained nPDFs are released as a parametrization called EPS08.

  7. Stability and activity of alcohol dehydrogenases in W/O-microemulsions: enantioselective reduction including cofactor regeneration.

    PubMed

    Orlich, B; Berger, H; Lade, M; Schomäcker, R

    2000-12-20

    Microemulsions provide an interesting alternative to classical methods for the conversion of less water-soluble substrates by alcohol dehydrogenase, but until now stability and activity were too low for economically useful processes. The activity and stability of the enzymes are dependent on the microemulsion composition, mostly the water and the surfactant concentration. Therefore, it is necessary to know the exact phase behavior of a given microemulsion reaction system and the corresponding enzyme behavior therein. Because of their economic and ecologic suitability polyethoxylated fatty alcohols were investigated concerning their phase behavior and their compatibility with enzymes in ternary mixtures. The phase behavior of Marlipal O13-60 (C13EO6 in industrial quality)/cyclohexane/water and its effect on the activity and stability of alcohol dehydrogenase from Yeast (YADH) and horse liver (HLADH) and the carbonyl reductase from Candida parapsilosis (CPCR) is presented in this study. Beside the macroscopic phase behavior of the reaction system, the viscosity of the system indicates structural changes of aggregates in the microemulsion. The changes of the enzyme activities with the composition are discussed on the basis of transitions from reverse micelles to swollen reverse micelles and finally, the transition to the phase separation. The formate dehydrogenase from Candida boidinii was used for the NADH-regeneration during reduction reactions. While the formate dehydrogenase did not show any kinetic effect on the microemulsion composition, the other enzymes show significant changes of activity and stability varying the water or surfactant concentration of the microemulsion. Under certain conditions, stability could be maintained with HLADH for several weeks. Successful experiments with semi-batch processes including cofactor regeneration and product separation were performed.

  8. Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase

    PubMed Central

    Abeysinghe, Hima Charika S.; Phillips, Ellie L.; Chin-Cheng, Heung; Beart, Philip M.; Roulston, Carli L.

    2016-01-01

    Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery. PMID:26927079

  9. Inflation including collapse of the wave function: the quasi-de Sitter case

    NASA Astrophysics Data System (ADS)

    León, Gabriel; Landau, Susana J.; Piccirilli, María Pía

    2015-08-01

    The precise physical mechanism describing the emergence of the seeds of cosmic structure from a perfect isotropic and homogeneous universe has not been fully explained by the standard version of inflationary models. To handle this shortcoming, D. Sudarsky and collaborators have developed a proposal: the self-induced collapse hypothesis. In this scheme, the objective collapse of the inflaton wave function is responsible for the emergence of inhomogeneity and anisotropy at all scales. In previous papers, the proposal was developed with an almost exact de Sitter space-time approximation for the background that led to a perfect scale-invariant power spectrum. In the present article, we consider a full quasi-de Sitter expansion and calculate the primordial power spectrum for three different choices of the self-induced collapse. The consideration of a quasi-de Sitter background allows us to distinguish departures from an exact scale-invariant power spectrum that are due to the inclusion of the collapse hypothesis. These deviations are also different from the prediction of standard inflationary models with a running spectral index. A comparison with the primordial power spectrum and the CMB temperature fluctuation spectrum preferred by the latest observational data is also discussed. From the analysis performed in this work, it follows that most of the collapse schemes analyzed in this paper are viable candidates to explain the present observations of the CMB fluctuation spectrum.

  10. How close can we get waves to wave functions, including potential?

    NASA Astrophysics Data System (ADS)

    Faletič, Sergej

    2016-05-01

    In the following article we show that mechanical waves on a braced string can have the same shapes as important wave functions in introductory quantum mechanics. A braced string is a string with additional transversal springs that serve as external "potential". The aim is not to suggest teaching quantum mechanics with these analogies. Instead, the aim is to provide students with some additional relevant experience in wave mechanics before they are introduced to quantum mechanics. We show how this experience can be used in a constructivist sense as the basis for building quantum concepts. We consider energy transfer along such string and show that penetration of a wave into a region with high "potential" is not unexpected. We also consider energy transfer between two such strings and show that it can appear point-like even though the wave is an extended object. We also suggest that applying quantization of energy transfer to wave phenomena can explain some of the more difficult to accept features of quantum mechanics.

  11. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Functions of agents, including Central Registration..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of...

  12. Broken symmetry approach to density functional calculation of zero field splittings including anisotropic exchange interactions

    SciTech Connect

    Kessler, Eva M. V.; Schmitt, Sebastian; Wüllen, Christoph van

    2013-11-14

    The broken symmetry approach to the calculation of zero field splittings (or magnetic anisotropies) of multinuclear transition metal complexes is further developed. A procedure is suggested how to extract spin Hamiltonian parameters for anisotropic exchange from a set of broken symmetry density functional calculations. For isotropic exchange coupling constants J{sub ij}, the established procedure is retrieved, and anisotropic (or pseudodipolar) exchange coupling tensors D{sub ij} are obtained analogously. This procedure only yields the sum of the individual single-ion zero field splitting tensors D{sub i}. Therefore, a procedure based on localized orbitals has been developed to extract the individual single-ion contributions. With spin Hamiltonian parameters at hand, the zero field splittings of the individual spin multiplets are calculated by an exact diagonalization of the isotropic part, followed by a spin projection done numerically. The method is applied to the binuclear cation [LCr(OH){sub 3}CrL]{sup 3+} (L = 1,4,7-trimethyl-1,4,7-triazanonane) for which experimental zero field splittings for all low-energy spin states are known, and to the single-molecule magnet [Fe{sub 4}(CH{sub 3}C(CH{sub 2}O){sub 3}){sub 2}(dpm){sub 6}] (Hdpm = 2,2,6,6-tetramethylheptane-3,5-dione). In both these 3d compounds, the single-ion tensors mainly come from the spin-orbit interaction. Anisotropic exchange is dominated by the spin-dipolar interaction only for the chromium compound. Despite the rather small isotropic exchange couplings in the iron compound, spin-orbit and spin-dipolar contributions to anisotropic exchange are of similar size here.

  13. Contractile Function During Angiotensin-II Activation

    PubMed Central

    Zhang, Min; Prosser, Benjamin L.; Bamboye, Moradeke A.; Gondim, Antonio N.S.; Santos, Celio X.; Martin, Daniel; Ghigo, Alessandra; Perino, Alessia; Brewer, Alison C.; Ward, Christopher W.; Hirsch, Emilio; Lederer, W. Jonathan; Shah, Ajay M.

    2015-01-01

    Background Renin-angiotensin system activation is a feature of many cardiovascular conditions. Activity of myocardial reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2 or Nox2) is enhanced by angiotensin II (Ang II) and contributes to increased hypertrophy, fibrosis, and adverse remodeling. Recent studies found that Nox2-mediated reactive oxygen species production modulates physiological cardiomyocyte function. Objectives This study sought to investigate the effects of cardiomyocyte Nox2 on contractile function during increased Ang II activation. Methods We generated a cardiomyocyte-targeted Nox2-transgenic mouse model and studied the effects of in vivo and ex vivo Ang II stimulation, as well as chronic aortic banding. Results Chronic subpressor Ang II infusion induced greater cardiac hypertrophy in transgenic than wild-type mice but unexpectedly enhanced contractile function. Acute Ang II treatment also enhanced contractile function in transgenic hearts in vivo and transgenic cardiomyocytes ex vivo. Ang II–stimulated Nox2 activity increased sarcoplasmic reticulum (SR) Ca2+ uptake in transgenic mice, increased the Ca2+ transient and contractile amplitude, and accelerated cardiomyocyte contraction and relaxation. Elevated Nox2 activity increased phospholamban phosphorylation in both hearts and cardiomyocytes, related to inhibition of protein phosphatase 1 activity. In a model of aortic banding–induced chronic pressure overload, heart function was similarly depressed in transgenic and wild-type mice. Conclusions We identified a novel mechanism in which Nox2 modulates cardiomyocyte SR Ca2+ uptake and contractile function through redox-regulated changes in phospholamban phosphorylation. This mechanism can drive increased contractility in the short term in disease states characterized by enhanced renin-angiotensin system activation. PMID:26184620

  14. Functional activity monitoring from wearable sensor data.

    PubMed

    Nawab, S Hamid; Roy, Serge H; De Luca, Carlo J

    2004-01-01

    A novel approach is presented for the interpretation and use of EMG and accelerometer data to monitor, identify, and categorize functional motor activities in individuals whose movements are unscripted, unrestrained, and take place in the "real world". Our proposed solution provides a novel and practical way of conceptualizing physical activities that facilitates the deployment of modern signal processing and interpretation techniques to carry out activity monitoring. A hierarchical approach is adopted that is based upon: 1) blackboard and rule-based technology from artificial intelligence to support a process in which coarse-grained activity partitioning forms the context for finer-grained activity partitioning; 2) neural network technology to support initial activity classification; and 3) integrated processing and understanding of signals (IPUS) technology for revising the initial classifications to account for the high degrees of anticipated signal variability and overlap during freeform activity. PMID:17271844

  15. The EMT-activator ZEB1 induces bone metastasis associated genes including BMP-inhibitors

    PubMed Central

    Mock, Kerstin; Preca, Bogdan-Tiberius; Brummer, Tilman; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2015-01-01

    Tumor cell invasion, dissemination and metastasis is triggered by an aberrant activation of epithelial-to-mesenchymal transition (EMT), often mediated by the transcription factor ZEB1. Disseminating tumor cells must acquire specific features that allow them to colonize at different organ sites. Here we identify a set of genes that is highly expressed in breast cancer bone metastasis and activated by ZEB1. This gene set includes various secreted factors, e.g. the BMP-inhibitor FST, that are described to reorganize the bone microenvironment. By inactivating BMP-signaling, BMP-inhibitors are well-known to induce osteolysis in development and disease. We here demonstrate that the expression of ZEB1 and BMP-inhibitors is correlated with bone metastasis, but not with brain or lung metastasis of breast cancer patients. In addition, we show that this correlated expression pattern is causally linked, as ZEB1 induces the expression of the BMP-inhibitors NOG, FST and CHRDL1 both by directly increasing their gene transcription, as well as by indirectly suppressing their reduction via miR-200 family members. Consequently, ZEB1 stimulates BMP-inhibitor mediated osteoclast differentiation. These findings suggest that ZEB1 is not only driving EMT, but also contributes to the formation of osteolytic bone metastases in breast cancer. PMID:25973542

  16. Economic values of production and functional traits, including residual feed intake, in Finnish milk production.

    PubMed

    Hietala, P; Wolfová, M; Wolf, J; Kantanen, J; Juga, J

    2014-02-01

    Improving the feed efficiency of dairy cattle has a substantial effect on the economic efficiency and on the reduction of harmful environmental effects of dairy production through lower feeding costs and emissions from dairy farming. To assess the economic importance of feed efficiency in the breeding goal for dairy cattle, the economic values for the current breeding goal traits and the additional feed efficiency traits for Finnish Ayrshire cattle under production circumstances in 2011 were determined. The derivation of economic values was based on a bioeconomic model in which the profit of the production system was calculated, using the generated steady state herd structure. Considering beef production from dairy farms, 2 marketing strategies for surplus calves were investigated: (A) surplus calves were sold at a young age and (B) surplus calves were fattened on dairy farms. Both marketing strategies were unprofitable when subsidies were not included in the revenues. When subsidies were taken into account, a positive profitability was observed in both marketing strategies. The marginal economic values for residual feed intake (RFI) of breeding heifers and cows were -25.5 and -55.8 €/kg of dry matter per day per cow and year, respectively. The marginal economic value for RFI of animals in fattening was -29.5 €/kg of dry matter per day per cow and year. To compare the economic importance among traits, the standardized economic weight of each trait was calculated as the product of the marginal economic value and the genetic standard deviation; the standardized economic weight expressed as a percentage of the sum of all standardized economic weights was called relative economic weight. When not accounting for subsidies, the highest relative economic weight was found for 305-d milk yield (34% in strategy A and 29% in strategy B), which was followed by protein percentage (13% in strategy A and 11% in strategy B). The third most important traits were calving

  17. Design of a high-lift experiment in water including active flow control

    NASA Astrophysics Data System (ADS)

    Beutel, T.; Sattler, S.; El Sayed, Y.; Schwerter, M.; Zander, M.; Büttgenbach, S.; Leester-Schädel, M.; Radespiel, R.; Sinapius, M.; Wierach, P.

    2014-07-01

    This paper describes the structural design of an active flow-control experiment. The aim of the experiment is to investigate the increase in efficiency of an internally blown Coanda flap using unsteady blowing. The system uses tailor-made microelectromechanical (MEMS) pressure sensors to determine the state of the oncoming flow and an actuated lip to regulate the mass flow and velocity of a stream near a wall over the internally blown flap. Sensors and actuators are integrated into a highly loaded system that is extremely compact. The sensors are connected to a bus system that feeds the data into a real-time control system. The piezoelectric actuators using the d 33 effect at a comparable low voltage of 120 V are integrated into a lip that controls the blowout slot height. The system is designed for closed-loop control that efficiently avoids flow separation on the Coanda flap. The setup is designed for water-tunnel experiments in order to reduce the free-stream velocity and the system’s control frequency by a factor of 10 compared with that in air. This paper outlines the function and verification of the system’s main components and their development.

  18. Be BOLD: Encouraging Girls to Include Unstructured Bouts of Physical Activity into Daily Routines

    ERIC Educational Resources Information Center

    Hill, Kory; Williams, Gwynne M.

    2014-01-01

    Adolescent girls are less active than their male counterparts and physical activity levels tend to decline as one ages. One of the goals of concerned physical educators is to promote a physically active lifestyle and to teach skills and promote behaviors that will allow students to be active both in and out of school. This article presents a…

  19. Integrating Communication Skills into Functional Routines & Activities.

    ERIC Educational Resources Information Center

    Stremel, Kathleen

    This training module on integrating communication skills into functional routines and activities is from the Mississippi Early Education Program for Children with Multiple Disabilities, a program designed to train Individuals with Disabilities Education Act Part H service coordinators and service providers to use family centered strategies. The…

  20. Opiates and cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  1. Active control of environmental noise, VIII: increasing the response to primary source changes including unpredictable noise

    NASA Astrophysics Data System (ADS)

    Wright, S. E.; Atmoko, H.; Vuksanovic, B.

    2004-07-01

    Conventional adaptive cancellation systems using traditional transverse finite impulse response (FIR) filters, together with least mean square (LMS) adaptive algorithms, well known in active noise control, are slow to adapt to primary source changes. This makes them inappropriate for cancelling rapidly changing noise, including unpredictable noise such as speech and music. Secondly, the cancelling structures require considerable computational processing effort to adapt to primary source and plant changes, particularly for multi-channel systems. This paper describes methods to increase the adaptive speed to primary source changes in large enclosed spaces and outdoor environments. A method is described that increases the response to time varying periodic noise using traditional transverse FIR filters. Here a multi-passband filter, with individual variable adaptive step sizes for each passband is automatically adjusted according to the signal level in each band. This creates a similar adaptive response for all frequencies within the total pass-band, irrespective of amplitude, minimizing the signal distortion and increasing the combined adaptive speed. Unfortunately, there is a limit to the adaptive speed using the above method as classical transverse FIR filters have a finite adaptive speed given by the stability band zero bandwidth. For rapidly changing periodic noise and unpredictable non-stationary noise, a rapid to instantaneous response is required. In this case the on-line adaptive FIR filters are dispensed with and replaced by a time domain solution that gives virtually instantaneous cancellation response (infinite adaptive speed) to primary source changes, and is computationally efficient.

  2. Radio Properties of Low Redshift Broad Line Active Galactic Nuclei Including Multiple Component Radio Sources

    NASA Astrophysics Data System (ADS)

    Rafter, Stephen E.

    2010-01-01

    We present results on the radio properties of a low redshift (z < 0.35) sample of 8434 broad line active galactic nuclei (AGNs) from the Sloan Digital Sky Survey after correlating the optical sources with radio sources in the Faint Images of the Radio Sky at Twenty-Centimeters survey. We find that 10% of our sample has radio emission < 4" away from the optical counterpart (core-only sources), and 1% has significant extended emission that must be taken into account when calculating the total radio luminosity (multi-component sources). Association of the extended radio emission is established by the proximity to the optical source, physical connection of jets and lobes, or large scale symmetry like in classic FRIIs. From these data we find an FRI/FRII luminosity dividing line like that found by Fanaroff & Riley (1974), where we use our core-only sources as proxies for FRIs, and our multi-component sources for the FRIIs. We find a bimodal distribution for the radio loudness (R = L(radio)/L(opt)) where the lower radio luminosity core-only sources appear as a population separate from the multi-component extended sources, compared with no evidence for bimodality when just the core-only sources are used. We also find that a log(R) value of 1.75 is well suited to separate the FRIs from the FRIIs, and that the R bimodality seen here is really a manifestation of the FRI/FRII break originally found by Fanaroff & Riley (1974). We find modest trends in the radio loud fraction as a function of Eddington ratio and black hole mass, where the fraction of RL AGNs decreases with increasing Eddington ratio, and increases when the black hole mass is above 2 x 108 solar masses.

  3. A current type PWM rectifier with active damping function

    SciTech Connect

    Sato, Yukihiko; Kataoka, Teruo

    1995-12-31

    A new control method for current type PWM rectifiers which can provide active damping function is presented. This damping function is effective only on the harmonic components of ac input current selectively. Thus steady state waveform distortion and transient oscillation of the input current are reduced by the active damping effects. The active damping function can be realized by feed-back control of an LC filter connected to the ac side of the rectifier, and it does not require any additional components in the main circuits, permitting a simple circuit configuration. The control system of the proposed PWM rectifier is analyzed by using a simple block diagram developed in the present paper. From the analytical results, the influence of the circuit parameters and control delay on the active damping effects and the stability of the operation is clarified to establish the design method. To confirm the effectiveness of the active damping function, some results of basic experiments are included. As an example of application of the active damping function, the proposed rectifier is applied to reduce the harmonic currents generated by conventional rectifiers operating in parallel with the proposed rectifier. Some experimental results in this application are also included.

  4. A current-type PWM rectifier with active damping function

    SciTech Connect

    Sato, Yukihiko; Kataoka, Teruo

    1996-05-01

    A new control method for current-type pulse-width modulation (PWM) rectifiers which can provide active damping function is presented. This damping function is effective only on the harmonic components of ac input current selectively. Thus steady-state waveform distortion and transient oscillation of the input current are reduced by the active damping effects. The active damping function can be realized by feedback control of an LC filter connected to the ac side of the rectifier, and it does not require any additional components in the main circuits, permitting a simple circuit configuration. The control system of the proposed PWM rectifier is analyzed by using a simple block diagram developed in the present paper. From the analytical results, the influence of the circuit parameters and control delay on the active damping effects and the stability of the operation are clarified to establish the design method. To confirm the effectiveness of the active damping function, some results of basic experiments are included. As an example of application of the active damping function, the proposed rectifier is applied to reduce the harmonic currents generated by conventional rectifiers operating in parallel with the proposed rectifier. Some experimental results in this application are also included.

  5. An efficient algorithm for solving coupled Schroedinger type ODE`s, whose potentials include {delta}-functions

    SciTech Connect

    Gousheh, S.S.

    1996-01-01

    I have used the shooting method to find the eigenvalues (bound state energies) of a set of strongly coupled Schroedinger type equations. I have discussed the advantages of the shooting method when the potentials include {delta}-functions. I have also discussed some points which are universal in these kind of problems, whose use make the algorithm much more efficient. These points include mapping the domain of the ODE into a finite one, using the asymptotic form of the solutions, best use of the normalization freedom, and converting the {delta}-functions into boundary conditions.

  6. 45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 2 2011-10-01 2011-10-01 false Can NEW Program activities include job market assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... Program Design and Operations § 287.130 Can NEW Program activities include job market assessments,...

  7. 45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 2 2012-10-01 2012-10-01 false Can NEW Program activities include job market assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... Program Design and Operations § 287.130 Can NEW Program activities include job market assessments,...

  8. 45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Can NEW Program activities include job market assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... Program Design and Operations § 287.130 Can NEW Program activities include job market assessments,...

  9. 45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 2 2014-10-01 2012-10-01 true Can NEW Program activities include job market assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... Program Design and Operations § 287.130 Can NEW Program activities include job market assessments,...

  10. 45 CFR 287.130 - Can NEW Program activities include job market assessments, job creation and economic development...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 2 2013-10-01 2012-10-01 true Can NEW Program activities include job market assessments, job creation and economic development activities? 287.130 Section 287.130 Public Welfare... Program Design and Operations § 287.130 Can NEW Program activities include job market assessments,...

  11. A predator-prey model with a holling type I functional response including a predator mutual interference

    USGS Publications Warehouse

    Seo, G.; DeAngelis, D.L.

    2011-01-01

    The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

  12. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  13. Using Assistive Technology Adaptations To Include Students with Learning Disabilities in Cooperative Learning Activities.

    ERIC Educational Resources Information Center

    Bryant, Diane Pedrotty; Bryant, Brian R.

    1998-01-01

    Discusses a process for integrating technology adaptations for students with learning disabilities into cooperative-learning activities in terms of three components: (1) selecting adaptations; (2) monitoring use of adaptations during cooperative-learning activities; and (3) evaluating the adaptations' effectiveness. Barriers to and support systems…

  14. The NLP toxin family in Phytophthora sojae includes rapidly evolving groups that lack necrosis-inducing activity.

    PubMed

    Dong, Suomeng; Kong, Guanghui; Qutob, Dinah; Yu, Xiaoli; Tang, Junli; Kang, Jixiong; Dai, Tingting; Wang, Hai; Gijzen, Mark; Wang, Yuanchao

    2012-07-01

    Necrosis- and ethylene-inducing-like proteins (NLP) are widely distributed in eukaryotic and prokaryotic plant pathogens and are considered to be important virulence factors. We identified, in total, 70 potential Phytophthora sojae NLP genes but 37 were designated as pseudogenes. Sequence alignment of the remaining 33 NLP delineated six groups. Three of these groups include proteins with an intact heptapeptide (Gly-His-Arg-His-Asp-Trp-Glu) motif, which is important for necrosis-inducing activity, whereas the motif is not conserved in the other groups. In total, 19 representative NLP genes were assessed for necrosis-inducing activity by heterologous expression in Nicotiana benthamiana. Surprisingly, only eight genes triggered cell death. The expression of the NLP genes in P. sojae was examined, distinguishing 20 expressed and 13 nonexpressed NLP genes. Real-time reverse-transcriptase polymerase chain reaction results indicate that most NLP are highly expressed during cyst germination and infection stages. Amino acid substitution ratios (Ka/Ks) of 33 NLP sequences from four different P. sojae strains resulted in identification of positive selection sites in a distinct NLP group. Overall, our study indicates that expansion and pseudogenization of the P. sojae NLP family results from an ongoing birth-and-death process, and that varying patterns of expression, necrosis-inducing activity, and positive selection suggest that NLP have diversified in function.

  15. Diffractive laser beam homogenizer including a photo-active material and method of fabricating the same

    SciTech Connect

    Bayramian, Andy J; Ebbers, Christopher A; Chen, Diana C

    2014-05-20

    A method of manufacturing a plurality of diffractive optical elements includes providing a partially transmissive slide, providing a first piece of PTR glass, and directing first UV radiation through the partially transmissive slide to impinge on the first piece of PTR glass. The method also includes exposing predetermined portions of the first piece of PTR glass to the first UV radiation and thermally treating the exposed first piece of PTR glass. The method further includes providing a second piece of PTR glass and directing second UV radiation through the thermally treated first piece of PTR glass to impinge on the second piece of PTR glass. The method additionally includes exposing predetermined portions of the second piece of PTR glass to the second UV radiation, thermally treating the exposed second piece of PTR glass, and repeating providing and processing of the second piece of PTR glass using additional pieces of PTR glass.

  16. In vitro and in vivo anti-plasmodial activity of essential oils, including hinokitiol.

    PubMed

    Fujisaki, Ryuichi; Kamei, Kiyoko; Yamamura, Mariko; Nishiya, Hajime; Inouye, Shigeharu; Takahashi, Miki; Abe, Shigeru

    2012-03-01

    Abstract. The anti-plasmodial activity of 47 essential oils and 10 of their constituents were screened for in vitro activity against Plasmodium falciparum. Five of these essential oils (sandalwood, caraway, monarda, nutmeg, and Thujopsis dolabrata var. hondai) and 2 constituents (thymoquinone and hinokitiol) were found to be active against P. falciparum in vitro, with 50% inhibitory concentration (IC50) values equal to or less than 1.0 microg/ml. Furthermore, in vivo analysis using a rodent model confirmed the anti-plasmodial potential of subcutaneously administered sandalwood oil, and percutaneously administered hinokitiol and caraway oil against rodent P. berghei. Notably, these oils showed no efficacy when administered orally, intraperitoneally or intravenously. Caraway oil and hinokitiol dissolved in carrier oil, applied to the skin of hairless mice caused high levels in the blood, with concentrations exceeding their IC50 values. PMID:23082579

  17. In vitro and in vivo anti-plasmodial activity of essential oils, including hinokitiol.

    PubMed

    Fujisaki, Ryuichi; Kamei, Kiyoko; Yamamura, Mariko; Nishiya, Hajime; Inouye, Shigeharu; Takahashi, Miki; Abe, Shigeru

    2012-03-01

    Abstract. The anti-plasmodial activity of 47 essential oils and 10 of their constituents were screened for in vitro activity against Plasmodium falciparum. Five of these essential oils (sandalwood, caraway, monarda, nutmeg, and Thujopsis dolabrata var. hondai) and 2 constituents (thymoquinone and hinokitiol) were found to be active against P. falciparum in vitro, with 50% inhibitory concentration (IC50) values equal to or less than 1.0 microg/ml. Furthermore, in vivo analysis using a rodent model confirmed the anti-plasmodial potential of subcutaneously administered sandalwood oil, and percutaneously administered hinokitiol and caraway oil against rodent P. berghei. Notably, these oils showed no efficacy when administered orally, intraperitoneally or intravenously. Caraway oil and hinokitiol dissolved in carrier oil, applied to the skin of hairless mice caused high levels in the blood, with concentrations exceeding their IC50 values.

  18. Electrode including porous particles with embedded active material for use in a secondary electrochemical cell

    DOEpatents

    Vissers, Donald R.; Nelson, Paul A.; Kaun, Thomas D.; Tomczuk, Zygmunt

    1978-04-25

    Particles of carbonaceous matrices containing embedded electrode active material are prepared for vibratory loading within a porous electrically conductive substrate. In preparing the particles, active materials such as metal chalcogenides, solid alloys of alkali or alkaline earth metals along with other metals and their oxides in powdered or particulate form are blended with a thermosetting resin and particles of a volatile to form a paste mixture. The paste is heated to a temperature at which the volatile transforms into vapor to impart porosity at about the same time as the resin begins to cure into a rigid, solid structure. The solid structure is then comminuted into porous, carbonaceous particles with the embedded active material.

  19. Benchmark Calculations of Energetic Properties of Groups 4 and 6 Transition Metal Oxide Nanoclusters Including Comparison to Density Functional Theory.

    PubMed

    Fang, Zongtang; Both, Johan; Li, Shenggang; Yue, Shuwen; Aprà, Edoardo; Keçeli, Murat; Wagner, Albert F; Dixon, David A

    2016-08-01

    The heats of formation and the normalized clustering energies (NCEs) for the group 4 and group 6 transition metal oxide (TMO) trimers and tetramers have been calculated by the Feller-Peterson-Dixon (FPD) method. The heats of formation predicted by the FPD method do not differ much from those previously derived from the NCEs at the CCSD(T)/aT level except for the CrO3 nanoclusters. New and improved heats of formation for Cr3O9 and Cr4O12 were obtained using PW91 orbitals instead of Hartree-Fock (HF) orbitals. Diffuse functions are necessary to predict accurate heats of formation. The fluoride affinities (FAs) are calculated with the CCSD(T) method. The relative energies (REs) of different isomers, NCEs, electron affinities (EAs), and FAs of (MO2)n (M = Ti, Zr, Hf, n = 1-4) and (MO3)n (M = Cr, Mo, W, n = 1-3) clusters have been benchmarked with 55 exchange-correlation density functional theory (DFT) functionals including both pure and hybrid types. The absolute errors of the DFT results are mostly less than ±10 kcal/mol for the NCEs and the EAs and less than ±15 kcal/mol for the FAs. Hybrid functionals usually perform better than the pure functionals for the REs and NCEs. The performance of the two types of functionals in predicting EAs and FAs is comparable. The B1B95 and PBE1PBE functionals provide reliable energetic properties for most isomers. Long range corrected pure functionals usually give poor FAs. The standard deviation of the absolute error is always close to the mean errors, and the probability distributions of the DFT errors are often not Gaussian (normal). The breadth of the distribution of errors and the maximum probability are dependent on the energy property and the isomer. PMID:27384926

  20. Benchmark Calculations of Energetic Properties of Groups 4 and 6 Transition Metal Oxide Nanoclusters Including Comparison to Density Functional Theory.

    PubMed

    Fang, Zongtang; Both, Johan; Li, Shenggang; Yue, Shuwen; Aprà, Edoardo; Keçeli, Murat; Wagner, Albert F; Dixon, David A

    2016-08-01

    The heats of formation and the normalized clustering energies (NCEs) for the group 4 and group 6 transition metal oxide (TMO) trimers and tetramers have been calculated by the Feller-Peterson-Dixon (FPD) method. The heats of formation predicted by the FPD method do not differ much from those previously derived from the NCEs at the CCSD(T)/aT level except for the CrO3 nanoclusters. New and improved heats of formation for Cr3O9 and Cr4O12 were obtained using PW91 orbitals instead of Hartree-Fock (HF) orbitals. Diffuse functions are necessary to predict accurate heats of formation. The fluoride affinities (FAs) are calculated with the CCSD(T) method. The relative energies (REs) of different isomers, NCEs, electron affinities (EAs), and FAs of (MO2)n (M = Ti, Zr, Hf, n = 1-4) and (MO3)n (M = Cr, Mo, W, n = 1-3) clusters have been benchmarked with 55 exchange-correlation density functional theory (DFT) functionals including both pure and hybrid types. The absolute errors of the DFT results are mostly less than ±10 kcal/mol for the NCEs and the EAs and less than ±15 kcal/mol for the FAs. Hybrid functionals usually perform better than the pure functionals for the REs and NCEs. The performance of the two types of functionals in predicting EAs and FAs is comparable. The B1B95 and PBE1PBE functionals provide reliable energetic properties for most isomers. Long range corrected pure functionals usually give poor FAs. The standard deviation of the absolute error is always close to the mean errors, and the probability distributions of the DFT errors are often not Gaussian (normal). The breadth of the distribution of errors and the maximum probability are dependent on the energy property and the isomer.

  1. Physical Activity Programs in Higher Education: Modifying Net/Wall Games to Include Individuals with Disabilities

    ERIC Educational Resources Information Center

    Braga, Luciana; Tracy, Julia F.; Taliaferro, Andrea R.

    2015-01-01

    The growing number of students with disabilities in higher education settings has presented challenges for instructors with regards to appropriate inclusion. Concerning physical activity courses in higher education, instructors may not have the knowledge or resources to make modifications and accommodations that will ultimately result in…

  2. Observing a fictitious stressful event: haematological changes, including circulating leukocyte activation.

    PubMed

    Mian, Rubina; Shelton-Rayner, Graham; Harkin, Brendan; Williams, Paul

    2003-03-01

    The aim of this study was to assess the effect of watching a psychological stressful event on the activation of leukocytes in healthy human volunteers. Blood samples were obtained from 32 healthy male and female subjects aged between 20 and 26 years before, during and after either watching an 83-minute horror film that none of the subjects had previously seen (The Texas Chainsaw Massacre, 1974) or by sitting quietly in a room (control group). Total differential cell counts, leukocyte activation as measured by the nitroblue tetrazolium (NBT) test, heart rate and blood pressure (BP) measurements were taken at defined time points. There were significant increases in peripheral circulating leukocytes, the number of activated circulating leukocytes, haemoglobin (Hb) concentration and haematocrit (Hct) in response to the stressor. These were accompanied by significant increases in heart rate, systolic and diastolic BP (P<0.05 from baseline). This is the first reported study on the effects of observing a psychologically stressful, albeit fictitious event on circulating leukocyte numbers and the state of leukocyte activation as determined by the nitrotetrazolium test.

  3. Sixty Minutes of Physical Activity per Day Included within Preschool Academic Lessons Improves Early Literacy

    ERIC Educational Resources Information Center

    Kirk, Stacie M.; Kirk, Erik P.

    2016-01-01

    Background: The effects of increases in physical activity (PA) on early literacy skills in preschool children are not known. Methods: Fifty-four African-American preschool children from a low socioeconomic urban Head Start participated over 8 months. A 2-group, quasi-experimental design was used with one preschool site participating in the PA…

  4. Population and Human Development: A Course Curriculum Including Lesson Plans, Activities and Bibliography.

    ERIC Educational Resources Information Center

    Murphy, Elaine M.

    This course outline suggests materials and learning activities on the interrelated causes and consequences of population growth and other population concerns. Designed to educate general college audiences, it is also intended for use as a preservice course for teachers. In addition, the course can be modified for high school students. The course…

  5. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE ALMONDS GROWN IN CALIFORNIA Administrative Rules and Regulations § 981.441 Credit for market... each activity shall be to promote the sale, consumption or use of California almonds, and nothing... in California almond growing counties with more than 1,000 bearing acres: Provided, That...

  6. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE ALMONDS GROWN IN CALIFORNIA Administrative Rules and Regulations § 981.441 Credit for market... each activity shall be to promote the sale, consumption or use of California almonds, and nothing... in California almond growing counties with more than 1,000 bearing acres: Provided, That...

  7. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURE ALMONDS GROWN IN CALIFORNIA Administrative Rules and Regulations § 981.441 Credit for market... each activity shall be to promote the sale, consumption or use of California almonds, and nothing... in California almond growing counties with more than 1,000 bearing acres: Provided, That...

  8. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE ALMONDS GROWN IN CALIFORNIA Administrative Rules and Regulations § 981.441 Credit for market... each activity shall be to promote the sale, consumption or use of California almonds, and nothing... in California almond growing counties with more than 1,000 bearing acres: Provided, That...

  9. Backyards and Butterflies: Ways to Include Children with Disabilities in Outdoor Activities.

    ERIC Educational Resources Information Center

    Greenstein, Doreen; And Others

    This sourcebook is designed for children, parents, and families, detailing ideas for outdoor play and learning activities, with emphasis on involving children with disabilities in outdoor play. A rural perspective permeates the guide, although each chapter contains ideas for making outdoor environments more accessible and safer for all children,…

  10. Beyond Right or Wrong: Challenges of Including Creative Design Activities in the Classroom

    ERIC Educational Resources Information Center

    Brennan, Karen

    2015-01-01

    In this article, we explore challenges encountered by K-12 educators in establishing classroom cultures that support creative learning activities with the Scratch programming language. Providing opportunities for students to understand and to build capacities for creative work was described by many of the teachers that we interviewed as a central…

  11. Space Resources for Teachers: Biology, Including Suggestions for Classroom Activities and Laboratory Experiments.

    ERIC Educational Resources Information Center

    Lee, Tom E.; And Others

    This compilation of resource units concerns the latest developments in space biology. Some of the topics included are oxygen consumption, temperature, radiation, rhythms, weightlessness, acceleration and vibration stress, toxicity, and sensory and perceptual problems. Many of the topics are interdisciplinary and relate biology, physiology,…

  12. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... relations purposes, including E-commerce (mail ordering through the Internet): Provided, That Credit-Back...-Back is requested. (e) The following requirements shall apply to Credit-Back for all promotional... and Canada, paragraph (e)(5) of this section shall also apply. (2) The clear and evident purpose...

  13. In vitro bactericidal activity of aminoglycosides, including the next-generation drug plazomicin, against Brucella spp.

    PubMed

    Olsen, Steven C; Carlson, Steve A

    2015-01-01

    Plazomicin is a next-generation aminoglycoside with a potentially unique set of clinical characteristics compared with other aminoglycosides. This study assessed the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of plazomicin against 15 clinical isolates as well as three reference strains representing Brucella abortus, Brucella melitensis and Brucella suis. These data were compared with those obtained for six other aminoglycosides and two aminocyclitols. Plazomicin and gentamicin were the only drugs demonstrating bactericidal activity towards two of the three Brucella spp., whilst plazomicin was the only drug exhibiting bactericidal activity against B. suis. This is the first study to assess the bactericidal nature of plazomicin against Brucella spp. in vitro. PMID:25459738

  14. Model of local temperature changes in brain upon functional activation.

    PubMed

    Collins, Christopher M; Smith, Michael B; Turner, Robert

    2004-12-01

    Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12 degrees C and are well within the range reported in recent experimental studies involving human subjects.

  15. Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

    PubMed

    Jones, Ronald N; Critchley, Ian A; Whittington, William L H; Janjic, Nebojsa; Pottumarthy, Sudha

    2005-12-01

    We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon

  16. Phytophthora infestans Has a Plethora of Phospholipase D Enzymes Including a Subclass That Has Extracellular Activity

    PubMed Central

    Meijer, Harold J. G.; Hassen, Hussen Harrun; Govers, Francine

    2011-01-01

    In eukaryotes phospholipase D (PLD) is involved in many cellular processes. Currently little is known about PLDs in oomycetes. Here we report that the oomycete plant pathogen Phytophthora infestans has a large repertoire of PLDs divided over six subfamilies: PXPH-PLD, PXTM-PLD, TM-PLD, PLD-likes, and type A and B sPLD-likes. Since the latter have signal peptides we developed a method using metabolically labelled phospholipids to monitor if P. infestans secretes PLD. In extracellular medium of ten P. infestans strains PLD activity was detected as demonstrated by the production of phosphatidic acid and the PLD specific marker phosphatidylalcohol. PMID:21423760

  17. Phytophthora infestans has a plethora of phospholipase D enzymes including a subclass that has extracellular activity.

    PubMed

    Meijer, Harold J G; Hassen, Hussen Harrun; Govers, Francine

    2011-01-01

    In eukaryotes phospholipase D (PLD) is involved in many cellular processes. Currently little is known about PLDs in oomycetes. Here we report that the oomycete plant pathogen Phytophthora infestans has a large repertoire of PLDs divided over six subfamilies: PXPH-PLD, PXTM-PLD, TM-PLD, PLD-likes, and type A and B sPLD-likes. Since the latter have signal peptides we developed a method using metabolically labelled phospholipids to monitor if P. infestans secretes PLD. In extracellular medium of ten P. infestans strains PLD activity was detected as demonstrated by the production of phosphatidic acid and the PLD specific marker phosphatidylalcohol. PMID:21423760

  18. Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation

    PubMed Central

    Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

    2014-01-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice. PMID:25409232

  19. A Methodology for Post Operational Clean Out of a Highly Active Facility Including Solids Behaviour - 12386

    SciTech Connect

    Edmondson, Michael J.; Ward, Tracy R.; Maxwell, Lisa J.

    2012-07-01

    The Highly Active Liquor Evaporation and Storage (HALES) plant at Sellafield handles acidic fission product containing liquor with typical activities of the order of 18x10{sup 9} Bq/ml. A strategy experimental feedback approach has been used to establish a wash regime for the Post Operational Clean Out (POCO) of the oldest storage tanks for this liquor. Two different wash reagents have been identified as being potentially suitable for removal of acid insoluble fission product precipitates. Ammonium carbamate and sodium carbonate yield similar products during the proposed wash cycle. The proposed wash reagents provide dissolution of caesium phosphomolybdate (CPM) and zirconium molybdate (ZM) solid phases but yields a fine, mobile precipitate of metal carbonates from the Highly Active Liquor (HAL) supernate. Addition of nitric acid to the wash effluent can cause CPM to precipitate where there is sufficient caesium and phosphorous available. Where they are not present (from ZM dissolution) the nitric acid addition initially produces a nitrate precipitate which then re-dissolves, along with the metal carbonates, to give a solid-free solution. The different behaviour of the two solids during the wash cycle has led to the proposal for an amended flowsheet. Additional studies on the potential to change the morphology of crystallising ZM have presented opportunities for changing the rheology of ZM sediments through doping with tellurium or particular organic acids. Two different wash reagents have been identified as being potentially suitable for the POCO of HALES Oldside HASTs. AC and SC both yield similar products during the proposed wash cycle. However, the different behaviour of the two principle HAL solids, CPM and ZM, during the wash cycle has led to the proposal for an amended flowsheet. Additional studies on the potential to change the morphology of crystallising ZM have presented opportunities for changing its rheology through doping with tellurium or certain

  20. Nuclear Rocket Test Facility Decommissioning Including Controlled Explosive Demolition of a Neutron-Activated Shield Wall

    SciTech Connect

    Michael Kruzic

    2007-09-01

    Located in Area 25 of the Nevada Test Site, the Test Cell A Facility was used in the 1960s for the testing of nuclear rocket engines, as part of the Nuclear Rocket Development Program. The facility was decontaminated and decommissioned (D&D) in 2005 using the Streamlined Approach For Environmental Restoration (SAFER) process, under the Federal Facilities Agreement and Consent Order (FFACO). Utilities and process piping were verified void of contents, hazardous materials were removed, concrete with removable contamination decontaminated, large sections mechanically demolished, and the remaining five-foot, five-inch thick radiologically-activated reinforced concrete shield wall demolished using open-air controlled explosive demolition (CED). CED of the shield wall was closely monitored and resulted in no radiological exposure or atmospheric release.

  1. LIPID PEROXIDATION GENERATES BIOLOGICALLY ACTIVE PHOSPHOLIPIDS INCLUDING OXIDATIVELY N-MODIFIED PHOSPHOLIPIDS

    PubMed Central

    Davies, Sean S.; Guo, Lilu

    2014-01-01

    Peroxidation of membranes and lipoproteins converts “inert” phospholipids into a plethora of oxidatively modified phospholipids (oxPL) that can act as signaling molecules. In this review, we will discuss four major classes of oxPL: mildly oxygenated phospholipids, phospholipids with oxidatively truncated acyl chains, phospholipids with cyclized acyl chains, and phospholipids that have been oxidatively N-modified on their headgroups by reactive lipid species. For each class of oxPL we will review the chemical mechanisms of their formation, the evidence for their formation in biological samples, the biological activities and signaling pathways associated with them, and the catabolic pathways for their elimination. We will end by briefly highlighting some of the critical questions that remain about the role of oxPL in physiology and disease. PMID:24704586

  2. Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase

    PubMed Central

    Sahonero-Canavesi, Diana X.; Sohlenkamp, Christian; Sandoval-Calderón, Mario; Lamsa, Anne; Pogliano, Kit; López-Lara, Isabel M.; Geiger, Otto

    2016-01-01

    Summary Phospholipids are well known for their membrane forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth. PMID:25711932

  3. Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase.

    PubMed

    Sahonero-Canavesi, Diana X; Sohlenkamp, Christian; Sandoval-Calderón, Mario; Lamsa, Anne; Pogliano, Kit; López-Lara, Isabel M; Geiger, Otto

    2015-09-01

    Phospholipids are well known for their membrane-forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth.

  4. Modeling the development of biofilm density including active bacteria, inert biomass, and extracellular polymeric substances.

    PubMed

    Laspidou, Chrysi S; Rittmann, Bruce E

    2004-01-01

    We present the unified multi-component cellular automaton (UMCCA) model, which predicts quantitatively the development of the biofilm's composite density for three biofilm components: active bacteria, inert or dead biomass, and extracellular polymeric substances. The model also describes the concentrations of three soluble organic components (soluble substrate and two types of soluble microbial products) and oxygen. The UMCCA model is a hybrid discrete-differential mathematical model and introduces the novel feature of biofilm consolidation. Our hypothesis is that the fluid over the biofilm creates pressures and vibrations that cause the biofilm to consolidate, or pack itself to a higher density over time. Each biofilm compartment in the model output consolidates to a different degree that depends on the age of its biomass. The UMCCA model also adds a cellular automaton algorithm that identifies the path of least resistance and directly moves excess biomass along that path, thereby ensuring that the excess biomass is distributed efficiently. A companion paper illustrates the trends that the UMCCA model is able to represent and shows a comparison with experimental results. PMID:15276752

  5. Ozone control of biological activity during Earth's history, including the KT catastrophe

    NASA Technical Reports Server (NTRS)

    Sheldon, W. R.

    1994-01-01

    There have been brief periods since the beginning of the Cambrian some 600 m.y. ago when mass extinctions destroyed a significant fraction of living species. The most widely studied of these events is the catastrophe at the KT boundary that ended the long dominance of the dinosaurs. In addition to mass extinctions, there is another profound discontinuity in the history of Earth's biota, the explosion of life at the end of the Precambrian era which is an episode that is not explained well at all. For some 3 b.y. before the Cambrian, life had been present on Earth, but maintained a low level of activity which is an aspect of the biota that is puzzling, especially during the last two-thirds of that period. During the last 2 b.y. before the Cambrian, conditions at the Earth's surface were suitable for a burgeoning of the biota, according to most criteria: the oceans neither boiled nor were fozen solid during this time, and the atmosphere contained sufficient O for the development of animals. The purpose of this paper is to suggest that mass extinctions and the lackluster behavior of the Precambrian biota share a common cause: an inadequate amount of ozone in the atmosphere.

  6. Unification of dynamic density functional theory for colloidal fluids to include inertia and hydrodynamic interactions: derivation and numerical experiments.

    PubMed

    Goddard, B D; Nold, A; Savva, N; Yatsyshin, P; Kalliadasis, S

    2013-01-23

    Starting from the Kramers equation for the phase-space dynamics of the N-body probability distribution, we derive a dynamical density functional theory (DDFT) for colloidal fluids including the effects of inertia and hydrodynamic interactions (HI). We compare the resulting theory to extensive Langevin dynamics simulations for both hard rod systems and three-dimensional hard sphere systems with radially symmetric external potentials. As well as demonstrating the accuracy of the new DDFT, by comparing with previous DDFTs which neglect inertia, HI, or both, we also scrutinize the significance of including these effects. Close to local equilibrium we derive a continuum equation from the microscopic dynamics which is a generalized Navier-Stokes-like equation with additional non-local terms governing the effects of HI. For the overdamped limit we recover analogues of existing configuration-space DDFTs but with a novel diffusion tensor. PMID:23220969

  7. Cardiovascular function following reduced aerobic activity

    NASA Technical Reports Server (NTRS)

    Raven, P. B.; Welch-O'Connor, R. M.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure

  8. Phagocytic cell function in active brucellosis.

    PubMed Central

    Ocon, P; Reguera, J M; Morata, P; Juarez, C; Alonso, A; Colmenero, J D

    1994-01-01

    In this study, we analyzed phagocytic cell function in 51 patients with active brucellosis and its relationship with different clinical, serological, and evolutionary variables. A control group was made up of 30 blood donors of similar geographic extraction, age, and sex, with no previous history of brucellosis or known exposure ot the infection or specific antibodies. The investigations were carried out at the time of diagnosis, at the conclusion of treatment, and after 6 months of follow-up. Polymorphonuclear leukocyte adherence and nitroblue tetrazolium reduction in response to Brucella antigen were significantly increased in the patients at the time of diagnosis with respect to the control group. In contrast, chemotaxis in response to Brucella antigen and phagocytosis were significantly reduced in the patients with respect to the control group. The alterations in phagocytic cell function were greater in patients with bacteremia, with focal forms of the disease, or with a longer diagnostic delay. Most of these initial alterations tended to normalize with treatment, indicating their transient character. PMID:8112863

  9. Should Physical Activity Be Included in Nutrition Education? A Comparison of Nutrition Outcomes with and without In-Class Activities

    ERIC Educational Resources Information Center

    Palmer-Keenan, Debra M.; Corda, Kirsten

    2014-01-01

    Limited-resource adults' dietary intakes and nutrition behaviors improve as a result of Expanded Food and Nutrition Education Program (EFNEP)/Supplemental Nutrition Assistance Program Education (SNAP-Ed) participation; however, physical activity education is needed for improved health. The experimental study reported here assessed if spending…

  10. Motivational activation: a unifying hypothesis of orexin/hypocretin function.

    PubMed

    Mahler, Stephen V; Moorman, David E; Smith, Rachel J; James, Morgan H; Aston-Jones, Gary

    2014-10-01

    Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.

  11. Motivational activation: a unifying hypothesis of orexin/hypocretin function

    PubMed Central

    Mahler, Stephen V; Moorman, David E; Smith, Rachel J; James, Morgan H; Aston-Jones, Gary

    2015-01-01

    Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system. PMID:25254979

  12. MSTor: A program for calculating partition functions, free energies, enthalpies, entropies, and heat capacities of complex molecules including torsional anharmonicity

    NASA Astrophysics Data System (ADS)

    Zheng, Jingjing; Mielke, Steven L.; Clarkson, Kenneth L.; Truhlar, Donald G.

    2012-08-01

    We present a Fortran program package, MSTor, which calculates partition functions and thermodynamic functions of complex molecules involving multiple torsional motions by the recently proposed MS-T method. This method interpolates between the local harmonic approximation in the low-temperature limit, and the limit of free internal rotation of all torsions at high temperature. The program can also carry out calculations in the multiple-structure local harmonic approximation. The program package also includes six utility codes that can be used as stand-alone programs to calculate reduced moment of inertia matrices by the method of Kilpatrick and Pitzer, to generate conformational structures, to calculate, either analytically or by Monte Carlo sampling, volumes for torsional subdomains defined by Voronoi tessellation of the conformational subspace, to generate template input files, and to calculate one-dimensional torsional partition functions using the torsional eigenvalue summation method. Catalogue identifier: AEMF_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMF_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 77 434 No. of bytes in distributed program, including test data, etc.: 3 264 737 Distribution format: tar.gz Programming language: Fortran 90, C, and Perl Computer: Itasca (HP Linux cluster, each node has two-socket, quad-core 2.8 GHz Intel Xeon X5560 “Nehalem EP” processors), Calhoun (SGI Altix XE 1300 cluster, each node containing two quad-core 2.66 GHz Intel Xeon “Clovertown”-class processors sharing 16 GB of main memory), Koronis (Altix UV 1000 server with 190 6-core Intel Xeon X7542 “Westmere” processors at 2.66 GHz), Elmo (Sun Fire X4600 Linux cluster with AMD Opteron cores), and Mac Pro (two 2.8 GHz Quad-core Intel Xeon

  13. Development of an oregano-based ointment with anti-microbial activity including activity against methicillin-resistant Staphlococcus aureus.

    PubMed

    Eng, William; Norman, Robert

    2010-04-01

    Increasing antibiotic resistance has prompted a search for new compounds with anti-microbial activity. In the authors' previous study, oregano extract was identified as one of the most potent anti-microbial compounds. The disk diffusion method was employed to assess the degree of inhibition against various microorganisms, and the bacteriostatic or bactericidal mechanism of action. Disk diffusion studies showed that oregano was found to be bacteriostatic for Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus, (MRSA) but bacteriocidal for seven other microorganisms. Pseudomonas aeruginosa could not be inhibited by oregano. An ointment consisting of 1-10% oregano could inhibit most organisms except for Proteus mirabilis and Proteus vulgaris, which required 20% and Pseudomonas which could not be inhibited even at the highest concentration of 80%. Oregano extracts can be formulated into an ointment that shows broad antimicrobial activity. Additional testing to assess tissue toxicity and other adverse reactions would be needed prior to human testing.

  14. Long-term follow-up of pulmonary function in patients cured from testicular cancer with combination chemotherapy including bleomycin.

    PubMed Central

    Lehne, G.; Johansen, B.; Fosså, S. D.

    1993-01-01

    A follow-up study of pulmonary function in two groups of patients with testicular cancer was performed 6-12 years after treatment. Both groups, 47 patients in each, had undergone retroperitoneal lymph node dissection (RPLND). Patients with pathological stage (ps) II had also received bleomycin (median 270 mg) and cisplatin (median 540 mg) in three or four courses which included vinblastine or etoposide. Patients in ps I and II were similar with respect to age, general health, observation period, inspired oxygen fraction (FiO2) and maximal arterial oxygen pressure (pO2) at RPLND, but four (8.2%) with psII disease developed densities on chest X-ray during chemotherapy. At the long-term follow-up the groups were similar with respect to physical exercise, smoking pattern, present drug treatment and history of cardiopulmonary disease. In both groups forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and single breath transfer factor for carbon monoxide (TLCO) were within normal limits, and no difference was found between the groups. The combined data for both groups showed that smoking was highly associated with impairment in TLCO (P = 0.005), and smoking frequency was negatively correlated to TLCO (P = 0.002). We conclude that 3-4 courses with bleomycin, cisplatin and etoposide/vinblastine in testicular cancer patients do not lead to long-term impairment of pulmonary function. PMID:7688978

  15. 20 CFR 641.856 - What functions and activities constitute administrative costs?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... management, accounting, and payroll systems) including the purchase, systems development, and operating costs..., including: (i) Accounting, budgeting, financial, and cash management functions; (ii) Procurement and... carrying out administrative activities or the overall management of the program; (5) Costs of...

  16. Immunomodulation of phloretin by impairing dendritic cell activation and function.

    PubMed

    Lin, Chi-Chen; Chu, Ching-Liang; Ng, Chin-Sheng; Lin, Ching-Yen; Chen, Der-Yuan; Pan, I-Hong; Huang, Kao-Jean

    2014-05-01

    Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-κB, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-γ production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases. PMID:24651121

  17. Building an Understanding of Functions: A Series of Activities for Pre-Calculus

    ERIC Educational Resources Information Center

    Carducci, Olivia M.

    2008-01-01

    Building block toys can be used to illustrate various concepts connected with functions including graphs and rates of change of linear and exponential functions, piecewise functions, and composition of functions. Five brief activities suitable for a pre-calculus course are described.

  18. Effects of Leisure Education Programme Including Sportive Activities on Perceived Freedom in Leisure of Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Ertuzun, Ezgi

    2015-01-01

    The objective of this experimental study is to determine the effect of leisure education programme including sportive activities on the perceived freedom in leisure of adolescents with mild intellectual disabilities. The research was designed with an experimental group (n = 37) and a control group (n = 34), and was conducted among a total of 71…

  19. 25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... other information required under 25 CFR 1000 subpart K. ... self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance...

  20. 25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... other information required under 25 CFR 1000 subpart K. ... self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance...

  1. 25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... other information required under 25 CFR 1000 subpart K. ... self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance...

  2. 25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... other information required under 25 CFR 1000 subpart K. ... self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance...

  3. 25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... other information required under 25 CFR 1000 subpart K. ... self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance...

  4. Age of acquisition and imageability ratings for a large set of words, including verbs and function words.

    PubMed

    Bird, H; Franklin, S; Howard, D

    2001-02-01

    Age of acquisition and imageability ratings were collected for 2,645 words, including 892 verbs and 213 function words. Words that were ambiguous as to grammatical category were disambiguated: Verbs were shown in their infinitival form, and nouns (where appropriate) were preceded by the indefinite article (such as to crack and a crack). Subjects were speakers of British English selected from a wide age range, so that differences in the responses across age groups could be compared. Within the subset of early acquired noun/verb homonyms, the verb forms were rated as later acquired than the nouns, and the verb homonyms of high-imageability nouns were rated as significantly less imageable than their noun counterparts. A small number of words received significantly earlier or later age of acquisition ratings when the 20-40 years and 50-80 years age groups were compared. These tend to comprise words that have come to be used more frequently in recent years (either through technological advances or social change), or those that have fallen out of common usage. Regression analyses showed that although word length, familiarity, and concreteness make independent contributions to the age of acquisition measure, frequency and imageability are the most important predictors of rated age of acquisition.

  5. Reconstruction of exciton wave functions of coupled quantum emitters including spin with ultrafast spectroscopy using localized nanooptical fields

    NASA Astrophysics Data System (ADS)

    Specht, Judith F.; Richter, Marten

    2016-04-01

    Coulomb-induced resonance energy transfer mechanisms between coupled nanostructures lead to the formation of new, delocalized exciton states. Their hybrid wave functions can be decomposed into the basis of local states of the uncoupled system by the use of coherent, spatially resolved spectroscopy. The suggested quantum state tomography protocol combines nanooptical fields with a four-wave mixing technique: At least one pulse of the pulse sequence is spatially localized at a specific quantum emitter. It was suggested to use nanoplasmonic structures together with pulse-shaped fields for the localization. In this paper, the method is applied to a system of two coupled semiconductor quantum dots. The basic reconstruction concept first proposed in Richter et al. (Phys Rev B 86:085308, 2012) and Schlosser et al. (New J Phys 15:025004, 2013) is extended to the case of including different spin states of the excitons in the quantum dots. For this purpose, the theoretical scheme has to be modified and the localized fields need the ability to change their polarization. We show that the application of the developed reconstruction scheme to two-dimensional spectra gives full access to the internal structure of the interacting quantum states.

  6. Optimal hematologic variables for oxygen transport, including P50, hemoglobin cooperativity, hematocrit, acid-base status, and cardiac function.

    PubMed

    Winslow, R M

    1988-01-01

    The two important blood properties that affect O2 delivery are the O2 equilibrium curve (OEC) and blood viscosity with its subsequent effect on flow (cardiac output). To quantitate these properties blood OEC's were analyzed in terms of the Adair 4-step oxygenation model and the resulting parameters were used to construct a computer nomogram to reproduce the OEC at any combination of effectors that regulate P50 (pH, PCO2, and 2,3-DPG). In this way, the P50 could be changed systematically and the effects on overall O2 transport could be studied. Hematocrit-viscosity-cardiac output relationships were taken from the literature and validated using data from human subjects with various pathological states and high-altitude natives. A model was then developed, using the Bohr integration, to predict the O2 transport function of blood under a variety of conditions including exercise and hypoxia. The results indicate that the optimal hematocrit is about 43-45%, even in hypoxia. The optimal P50, however, depends on the availability of O2: a high P50 is not necessarily beneficial in hypoxia and high cardiac output states. This model and general approach should prove useful in the design of blood substitutes.

  7. Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis.

    PubMed

    Heidegger, Isabel; Kern, Johann; Ofer, Philipp; Klocker, Helmut; Massoner, Petra

    2014-05-15

    We scrutinized the effect of insulin receptor (INSR) in addition to IGF1R in PCa using in vitro and in vivo models. In-vitro overexpression of IGF1R and INSRA, but not INSRB increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer cells (DU145, LNCaP, PC3). Opposite effects were induced by downregulation of IGF1R and total INSR, but not INSRB. In contrast to tumor cells, non-cancerous epithelial cells of the prostate (EP156T, RWPE-1) were inhibited on overexpression and stimulated by knockdown of receptors. In-vivo analyses using the chicken allantoic membrane assay confirmed the tumorigenic effects of IGF1R and INSR. Apart of promoting tumor growth, IGF1R and INSR overexpression also enhanced angiogenesis indicated by higher vessel density and increased number of desmin-immunoreactive pericytes. Our study underscores the oncogenic impact of IGF1R including significant effects on tumor growth, cell migration, sensitivity to apoptotic/chemotherapeutic agents and angiogenesis, and characterizes the INSR, in particular the isoform INSRA, as additional cancer-promoting receptor in prostate cancer. Both, the insulin-like growth factor receptor 1 and the insulin receptor exert oncogenic functions, thus proposing that both receptors need to be considered in therapeutic settings.

  8. A lipid chemotactic factor from anaerobic coryneform bacteria including Corynebacterium parvum with activity for macrophages and monocytes.

    PubMed Central

    Russell, R J; McInroy, R J; Wilkinson, P C; White, R G

    1976-01-01

    A lipid with chemoattractant (chemotactic) activity for mouse and guinea-pig macrophages and for human blood monocytes is released by anaerobic coryneform bacteria (including Corynebacterium parvum). The active lipid is associated with fibrillar structures which lie on the outside of the bacterial cell and are released spontaneously during growth. The lipid can also be extracted easily by a number of methods. The fibrils are loosely associated with a capsule-like structure composed largely of polysaccharide. Purification of the active lipid was achieved by chloroform-methanol extraction of the whole organisms yielding a chloroform-soluble fraction attracting mononuclear phagocytes at concentrations around 10 microgram/ml. The infra-red spectrum of this material showed lipid but no peptide or sugar. Thin-layer chromatography yielded twelve spots of which three had chemoattractant properties. The most active of these gave staining reactions consistent with the presence of phospholipid, the other two probably contained free fatty acids and triglycerides. Thin-layer electrophoresis also yielded an active phosphorus-containing spot. Saturated fatty acids of chain lengths found in the anaerobic coryne forms had weak monocyte-attractant activity. As the active material was progressively purified, its activity as a monocyte attractant weakened. Images Figure 2 Figure 3 Figure 4 PMID:1027716

  9. Activated Notch1 Target Genes during Embryonic Cell Differentiation Depend on the Cellular Context and Include Lineage Determinants and Inhibitors

    PubMed Central

    Meier-Stiegen, Franziska; Schwanbeck, Ralf; Bernoth, Kristina; Martini, Simone; Hieronymus, Thomas; Ruau, David; Zenke, Martin; Just, Ursula

    2010-01-01

    Background Notch receptor signaling controls developmental cell fates in a cell-context dependent manner. Although Notch signaling directly regulates transcription via the RBP-J/CSL DNA binding protein, little is known about the target genes that are directly activated by Notch in the respective tissues. Methodology/Principal Findings To analyze how Notch signaling mediates its context dependent function(s), we utilized a Tamoxifen-inducible system to activate Notch1 in murine embryonic stem cells at different stages of mesodermal differentiation and performed global transcriptional analyses. We find that the majority of genes regulated by Notch1 are unique for the cell type and vary widely dependent on other signals. We further show that Notch1 signaling regulates expression of genes playing key roles in cell differentiation, cell cycle control and apoptosis in a context dependent manner. In addition to the known Notch1 targets of the Hes and Hey families of transcriptional repressors, Notch1 activates the expression of regulatory transcription factors such as Sox9, Pax6, Runx1, Myf5 and Id proteins that are critically involved in lineage decisions in the absence of protein synthesis. Conclusion/Significance We suggest that Notch signaling determines lineage decisions and expansion of stem cells by directly activating both key lineage specific transcription factors and their repressors (Id and Hes/Hey proteins) and propose a model by which Notch signaling regulates cell fate commitment and self renewal in dependence of the intrinsic and extrinsic cellular context. PMID:20628604

  10. Antiviral activity of human Vδ2 T-cells against WNV includes both cytolytic and non-cytolytic mechanisms.

    PubMed

    Agrati, Chiara; Castilletti, Concetta; Cimini, Eleonora; Romanelli, Antonella; Lapa, Daniele; Quartu, Serena; Martini, Federico; Capobianchi, Maria Rosaria

    2016-04-01

    West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human γδ T-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of γδ T-cells in the protective immune response. Aim of this study was to analyze the cytolytic and non-cytolytic antiviral activity of human Vδ2 T-cells against WNV replication. The anti-WNV activity of soluble factor released by zoledronic acid (ZA)-activated Vδ2 T-cell lines and the cytotoxic capability of Vδ2 T-cell lines against WNV-infected cells were tested in vitro. The activation of Vδ2 T-cell lines was able to inhibit WNV replication through the release of soluble factors. IFN-γ is massively released by activated Vδ2 T-cell lines and is involved in the anti-WNV activity. Moreover, the Vδ2 T-cell lines can efficiently kill WNV-infected cells possibly through perforin-mediated mechanism. Altogether, our results provide insight into the effector functions of human Vδ2 T-cells against WNV. The possibility to target these cells by ZA, a commercially available drug used in humans, could potentially offer a new immunotherapeutic strategy for WNV infection. PMID:27196553

  11. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

    PubMed Central

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  12. The MRX Complex Ensures NHEJ Fidelity through Multiple Pathways Including Xrs2-FHA–Dependent Tel1 Activation

    PubMed Central

    Iwasaki, Daichi; Hayashihara, Kayoko; Shima, Hiroki; Higashide, Mika; Terasawa, Masahiro; Gasser, Susan M.; Shinohara, Miki

    2016-01-01

    Because DNA double-strand breaks (DSBs) are one of the most cytotoxic DNA lesions and often cause genomic instability, precise repair of DSBs is vital for the maintenance of genomic stability. Xrs2/Nbs1 is a multi-functional regulatory subunit of the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex, and its function is critical for the primary step of DSB repair, whether by homologous recombination (HR) or non-homologous end joining. In human NBS1, mutations result truncation of the N-terminus region, which contains a forkhead-associated (FHA) domain, cause Nijmegen breakage syndrome. Here we show that the Xrs2 FHA domain of budding yeast is required both to suppress the imprecise repair of DSBs and to promote the robust activation of Tel1 in the DNA damage response pathway. The role of the Xrs2 FHA domain in Tel1 activation was independent of the Tel1-binding activity of the Xrs2 C terminus, which mediates Tel1 recruitment to DSB ends. Both the Xrs2 FHA domain and Tel1 were required for the timely removal of the Ku complex from DSB ends, which correlates with a reduced frequency of imprecise end-joining. Thus, the Xrs2 FHA domain and Tel1 kinase work in a coordinated manner to maintain DSB repair fidelity. PMID:26990569

  13. Biological function of activation-induced cytidine deaminase (AID).

    PubMed

    Kumar, Ritu; DiMenna, Lauren J; Chaudhuri, Jayanta; Evans, Todd

    2014-01-01

    Activation-induced Cytidine Deaminase (AID) is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  14. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme.

    PubMed

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  15. Activities and Programs That Improve Children's Executive Functions.

    PubMed

    Diamond, Adele

    2012-10-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children's EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children's motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children's emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to "catch up" with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities. PMID:25328287

  16. Activities and Programs That Improve Children’s Executive Functions

    PubMed Central

    Diamond, Adele

    2014-01-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children’s EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children’s motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children’s emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to “catch up” with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities. PMID:25328287

  17. Activities and Programs That Improve Children's Executive Functions.

    PubMed

    Diamond, Adele

    2012-10-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children's EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children's motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children's emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to "catch up" with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities.

  18. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  19. Altered Hub Functioning and Compensatory Activations in the Connectome: A Meta-Analysis of Functional Neuroimaging Studies in Schizophrenia

    PubMed Central

    Crossley, Nicolas A.; Mechelli, Andrea; Ginestet, Cedric; Rubinov, Mikail; Bullmore, Edward T.; McGuire, Philip

    2016-01-01

    Background: Functional neuroimaging studies of schizophrenia have identified abnormal activations in many brain regions. In an effort to interpret these findings from a network perspective, we carried out a meta-analysis of this literature, mapping anatomical locations of under- and over-activation to the topology of a normative human functional connectome. Methods: We included 314 task-based functional neuroimaging studies including more than 5000 patients with schizophrenia and over 5000 controls. Coordinates of significant under- or over-activations in patients relative to controls were mapped to nodes of a normative connectome defined by a prior meta-analysis of 1641 functional neuroimaging studies of task-related activation in healthy volunteers. Results: Under-activations and over-activations were reported in a wide diversity of brain regions. Both under- and over-activations were significantly more likely to be located in hub nodes that constitute the “rich club” or core of the normative connectome. In a subset of 121 studies that reported both under- and over-activations in the same patients, we found that, in network terms, these abnormalities were located in close topological proximity to each other. Under-activation in a peripheral node was more frequently associated specifically with over-activation of core nodes than with over-activation of another peripheral node. Conclusions: Although schizophrenia is associated with altered brain functional activation in a wide variety of regions, abnormal responses are concentrated in hubs of the normative connectome. Task-specific under-activation in schizophrenia is accompanied by over-activation of topologically central, less functionally specialized network nodes, which may represent a compensatory response. PMID:26472684

  20. Function of streptokinase fragments in plasminogen activation.

    PubMed Central

    Shi, G Y; Chang, B I; Chen, S M; Wu, D H; Wu, H L

    1994-01-01

    Several peptide fragments of streptokinase (SK) were prepared by incubating SK with immobilized human plasmin (hPlm) and purified by h.p.l.c. with a reverse-phase phenyl column. The N-terminal sequences, amino acid compositions and molecular masses of these peptide fragments were determined. The SK peptide fragment of 36 kDa consisting of Ser60-Lys387 (SK-p), was the only peptide fragment that could be tightly bound to immobilized hPlm. Another three large SK peptide fragments, SK-m, SK-n and SK-o, with molecular masses of 7 kDa, 18 kDa and 30 kDa, and consisting of Ile1-Lys59, Glu148-Lys333, Ser60-Lys333 respectively, were also obtained from the supernatant of the reaction mixture. The purified SK-p had high affinity with hPlm and could activate human plasminogen (hPlg) with a kPlg one-sixth that of the native SK. SK-o had low affinity with hPlm and could also activate hPlg, although the catalytic constant was less than 1% of the native SK. SK-n, as well as SK-m, which is the N-terminal 59 amino acid peptide of the native SK, had no activator activity. However, SK-m could enhance the activator activity of both SK-o and SK-p and increase their second-order rate constants by two- and six-fold respectively. It was concluded from these studies that (1) SK-o, the Ser60-Lys333 peptide of SK, was essential for minimal SK activator activity, (2) the C-terminal peptide of SK-p, Ala334-Lys387, was essential for high affinity with hPlm, and (3) the N-terminal 59-amino-acid peptide was important in maintaining the proper conformation of SK to have its full activator activity. Images Figure 1 Figure 2 PMID:7998939

  1. In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains.

    PubMed

    Kohira, Naoki; West, Joshua; Ito, Akinobu; Ito-Horiyama, Tsukasa; Nakamura, Rio; Sato, Takafumi; Rittenhouse, Stephen; Tsuji, Masakatsu; Yamano, Yoshinori

    2015-11-16

    S-649266 is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Two sets of clinical isolate collections were used to evaluate the antimicrobial activity of S-649266 against Enterobacteriaceae. These sets included 617 global isolates collected between 2009 and 2011 and 233 β-lactamase-identified isolates, including 47 KPC-, 49 NDM-, 12 VIM-, and 8 IMP-producers. The MIC90 values of S-649266 against the first set of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae isolates were all ≤1 μg/ml, and there were only 8 isolates (1.3%) among these 617 clinical isolates with MIC values of ≥8 μg/ml. In the second set, the MIC values of S-649266 were ≤4 μg/ml against 109 strains among 116 KPC-producing and class B (metallo) carbapenemase-producing strains. In addition, S-649266 showed MIC values of ≤2 μg/ml against each of the 13 strains that produced other types of carbapenemases such as SME, NMC, and OXA-48. The mechanisms of the decreased susceptibility of 7 class B carbapenemase-producing strains with MIC values of ≥16 μg/ml are uncertain. This is the first report to demonstrate that S-649266, a novel siderophore cephalosporin, has significant antimicrobial activity against Enterobacteriaceae, including strains that produce carbapenemases such as KPC and NDM-1.

  2. Constructive feedforward neural networks using hermite polynomial activation functions.

    PubMed

    Ma, Liying; Khorasani, K

    2005-07-01

    In this paper, a constructive one-hidden-layer network is introduced where each hidden unit employs a polynomial function for its activation function that is different from other units. Specifically, both a structure level as well as a function level adaptation methodologies are utilized in constructing the network. The functional level adaptation scheme ensures that the "growing" or constructive network has different activation functions for each neuron such that the network may be able to capture the underlying input-output map more effectively. The activation functions considered consist of orthonormal Hermite polynomials. It is shown through extensive simulations that the proposed network yields improved performance when compared to networks having identical sigmoidal activation functions.

  3. Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City.

    PubMed

    Abdallah, Marie; Olafisoye, Olawole; Cortes, Christopher; Urban, Carl; Landman, David; Quale, John

    2015-03-01

    Eravacycline demonstrated in vitro activity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90 values, respectively, for Escherichia coli of 0.12/0.5 μg/ml, Klebsiella pneumoniae of 0.25/1 μg/ml, Enterobacter aerogenes of 0.25/1 μg/ml, Enterobacter cloacae 0.5/1 μg/ml, and Acinetobacter baumannii of 0.5/1 μg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. For A. baumannii, eravacycline MICs correlated with increased expression of the adeB gene. PMID:25534744

  4. [Biodiversity and Function Analyses of BIOLAK Activated Sludge Metagenome].

    PubMed

    Tian, Mei; Liu, Han-hu; Shen, Xin; Zhao, Fang-qing; Chen, Shuai; Yao, Yong-jia

    2015-05-01

    The BIOLAK is a multi-stage activated sludge process, which has been successfully promoted worldwide. However, the biological community and function of the BIOLAK activated sludge ( the core component in the process) have not been reported so far. In this study, taking Lianyungang Dapu Industrial Zone WWTP as an example, a large-scale metagenomic data (428 588 high-quality DNA sequences) of the BIOLAK activated sludge were obtained by means of a new generation of high-throughput sequencing technology. Amazing biodiversity was revealed in the BIOLAK activated sludge, which included 47 phyla, 872 genera and 1351 species. There were 33 phyla identified in the Bacteria domain (289 933 sequences). Proteohacteria was the most abundant phylum (62.54%), followed by Bacteroidetes (11.29%), Nitrospirae ( 5. 65%) and Planctomycetes (4.79%), suggesting that these groups played a key role in the BIOLAK wastewater treatment system. Among the 748 bacterial genera, Nitrospira (5.60%) was the most prevalent genus, which was a key group in the nitrogen cycle. Followed by Gemmatimonas (2.45%), which was an important genus in the biological phosphorus removal process. In Archaea domain (1019 sequences), three phyla and 39 genera were detected. In Eukaryota domain (1055 sequences), 60 genera and 10 phyla were identified, among which Ciliophora was the largest phylum (257 sequences). Meanwhile, 448 viral sequences were detected in the BIOLAK sludge metagenome, which were dominated by bacteriophages. The proportions of nitrogen, aromatic compounds and phosphorus metabolism in the BIOLAK sludge were 2.50%, 2.28% and 1.56%, respectively, which were higher than those in the sludge of United States and Australia. Among four processes of nitrogen metabolism, denitrification-related genes were most abundant (80.81%), followed by ammonification (12.78%), nitrification,(4.38%) and nitrogen fixation (2.04%). In conclusion, the BIOLAK activated sludge had amazing biodiversity, meanwhile

  5. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  6. OPIC: a kit for rapid merit function construction for use with all versions of OSLO, including OSLO EDU

    NASA Astrophysics Data System (ADS)

    Blandford, Brian

    2005-09-01

    The history of lens design software is sadly littered with accounts of excellent programs which fell by the wayside for lack of support. Others evolved through various package formats to form the foundation of today's very successful commercial software. One example of this is the Imperial College lens design program developed throughout the 1960s, 1970s and 1980s by Charles Wynne, Michael Kidger, Prudence Wormell, and others. This program (best known as the Kidger Optics Ltd SIGMA) produced many excellent designs over the years. One reason was that the ray patterns and weighting factors for operands in the default merit function had been carefully honed through experience, to produce rapid convergence on the global optimum from a likely starting point. This paper describes a suite of optimisation raysets and weighted operands written in the C-like OSLO compiled macro language CCL, and modeled on the Imperial College tradition. It is available for free download from http://www.lambdares.com/techsupport/kb/index.phtml. Its prime function is to provide a fast, easily understood introduction to merit function construction for the beginner. One version is for use on OSLO EDU, the free version of OSLO, which is also available from the Lambda Research Corporation website. This paper demonstrates how OPIC can be used to locate, from a remote starting point, the global minimum of the "monochromatic quartet," the lens design problem from the SPIE 1990 International Lens Design Conference.

  7. Usage Of New Activation Function In Neuro-Symbolic Integration

    SciTech Connect

    Sathasivam, Saratha

    2010-12-23

    New activation function is examined for its ability to accelerate the performance of doing logic programming in Hopfield network. This method has a higher capacity and upgrades the neuro symbolic integration. Computer simulations are carried out to validate the effectiveness of the new activation function. Empirical results obtained support our theory.

  8. Usage Of New Activation Function In Neuro-Symbolic Integration

    NASA Astrophysics Data System (ADS)

    Sathasivam, Saratha

    2010-12-01

    New activation function is examined for its ability to accelerate the performance of doing logic programming in Hopfield network. This method has a higher capacity and upgrades the neuro symbolic integration. Computer simulations are carried out to validate the effectiveness of the new activation function. Empirical results obtained support our theory.

  9. Multicomponent exercises including muscle power training enhance muscle mass, power output, and functional outcomes in institutionalized frail nonagenarians.

    PubMed

    Cadore, Eduardo L; Casas-Herrero, Alvaro; Zambom-Ferraresi, Fabricio; Idoate, Fernando; Millor, Nora; Gómez, Marisol; Rodriguez-Mañas, Leocadio; Izquierdo, Mikel

    2014-04-01

    This randomized controlled trial examined the effects of multicomponent training on muscle power output, muscle mass, and muscle tissue attenuation; the risk of falls; and functional outcomes in frail nonagenarians. Twenty-four elderly (91.9 ± 4.1 years old) were randomized into intervention or control group. The intervention group performed a twice-weekly, 12-week multicomponent exercise program composed of muscle power training (8-10 repetitions, 40-60 % of the one-repetition maximum) combined with balance and gait retraining. Strength and power tests were performed on the upper and lower limbs. Gait velocity was assessed using the 5-m habitual gait and the time-up-and-go (TUG) tests with and without dual-task performance. Balance was assessed using the FICSIT-4 tests. The ability to rise from a chair test was assessed, and data on the incidence and risk of falls were assessed using questionnaires. Functional status was assessed before measurements with the Barthel Index. Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography. The intervention group showed significantly improved TUG with single and dual tasks, rise from a chair and balance performance (P < 0.01), and a reduced incidence of falls. In addition, the intervention group showed enhanced muscle power and strength (P < 0.01). Moreover, there were significant increases in the total and high-density muscle cross-sectional area in the intervention group. The control group significantly reduced strength and functional outcomes. Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population.

  10. New approaches to enhance active steering system functionalities: preliminary results

    NASA Astrophysics Data System (ADS)

    Serarslan, Benan

    2014-09-01

    An important development of the steering systems in general is active steering systems like active front steering and steer-by-wire systems. In this paper the current functional possibilities in application of active steering systems are explored. A new approach and additional functionalities are presented that can be implemented to the active steering systems without additional hardware such as new sensors and electronic control units. Commercial active steering systems are controlling the steering angle depending on the driving situation only. This paper introduce methods for enhancing active steering system functionalities depending not only on the driving situation but also vehicle parameters like vehicle mass, tyre and road condition. In this regard, adaptation of the steering ratio as a function of above mentioned vehicle parameters is presented with examples. With some selected vehicle parameter changes, the reduction of the undesired influences on vehicle dynamics of these parameter changes has been demonstrated theoretically with simulations and with real-time driving measurements.

  11. Structural aspects of calcium-release activated calcium channel function

    PubMed Central

    Stathopulos, Peter B; Ikura, Mitsuhiko

    2013-01-01

    Store-operated calcium (Ca2+) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca2+ levels by signaling Ca2+ release activated Ca2+ channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca2+ elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca2+ sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca2+ sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID:24213636

  12. The alkaline single cell electrophoresis assay with eight mouse organs: results with 22 mono-functional alkylating agents (including 9 dialkyl N-nitrosoamines) and 10 DNA crosslinkers.

    PubMed

    Tsuda, S; Matsusaka, N; Madarame, H; Miyamae, Y; Ishida, K; Satoh, M; Sekihashi, K; Sasaki, Y F

    2000-04-13

    The genotoxicity of 22 mono-functional alkylating agents (including 9 dialkyl N-nitrosoamines) and 10 DNA crosslinkers selected from IARC (International Agency for Research on Cancer) groups 1, 2A, and 2B was evaluated in eight mouse organs with the alkaline single cell gel electrophoresis (SCGE) (comet) assay. Groups of four mice were treated once intraperitoneally at the dose at which micronucleus tests had been conducted, and the stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and/or 24 h later. All chemicals were positive in the SCGE assay in at least one organ. Of the 22 mono-functional alkylating agents, over 50% were positive in all organs except the brain and bone marrow. The two subsets of mono-functional alkylating agents differed in their bone marrow genotoxicity: only 1 of the 9 dialkyl N-nitrosoamines was positive in bone marrow as opposed to 8 of the 13 other alkylating agents, reflecting the fact that dialkyl N-nitrosoamines are poor micronucleus inducers in hematopoietic cells. The two groups of mono-functional alkylating agents also differ in hepatic carcinogenicity in spite of the fact that they are similar in hepatic genotoxicity. While dialkyl N-nitrosoamines produce tumors primarily in mouse liver, only one (styrene-7,8-oxide) out of 10 of the other type of mono-functional alkylating agents is a mouse hepatic carcinogen. Taking into consideration our previous results showing high concordance between hepatic genotoxicity and carcinogenicity for aromatic amines and azo compounds, a possible explanation for the discrepancy might be that chemicals that require metabolic activation show high concordance between genotoxicity and carcinogenicity in the liver. A high percent of the 10 DNA crosslinkers were positive in the SCGE assay in the gastrointestinal mucosa, but less than 50% were positive in the liver and lung. In this study, we allowed 10 min alkali-unwinding to obtain low and stable control values

  13. A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX.

    PubMed

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-09-01

    A recent chemical footprinting study in our laboratory suggested that region 1803-1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both regions 1803-1810 and 1811-1818 contribute to FVIIIa stability.

  14. A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX.

    PubMed

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-09-01

    A recent chemical footprinting study in our laboratory suggested that region 1803-1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both regions 1803-1810 and 1811-1818 contribute to FVIIIa stability. PMID:23884417

  15. A3 Domain Region 1803–1818 Contributes to the Stability of Activated Factor VIII and Includes a Binding Site for Activated Factor IX

    PubMed Central

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    A recent chemical footprinting study in our laboratory suggested that region 1803–1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803–1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803–1810 and 1811–1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811–1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811–1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803–1810 and FVIII/FV 1811–1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811–1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811–1818 contributes to FIXa binding. Both regions 1803–1810 and 1811–1818 contribute to FVIIIa stability. PMID:23884417

  16. Functional consequences of caspase activation in cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Communal, Catherine; Sumandea, Marius; de Tombe, Pieter; Narula, Jagat; Solaro, R. John; Hajjar, Roger J.

    2002-04-01

    Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including -actin, -actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of -actin and -actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using -adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity

  17. Validation of a high throughput flow cytometric in vitro micronucleus assay including assessment of metabolic activation in TK6 cells.

    PubMed

    Thougaard, Annemette V; Christiansen, Joan; Mow, Tomas; Hornberg, Jorrit J

    2014-12-01

    Genotoxicity is an unacceptable property for new drug candidates and we employ three screening assays during the drug discovery process to identify genotoxicity early and optimize chemical series. One of these methods is the flow cytometric in vitro micronucleus assay for which protocol optimizations have been described recently. Here, we report further validation of the assay in TK6 cells including assessment of metabolic activation. We first optimized assay conditions to allow for testing with and without metabolic activation in parallel in a 96-well plate format. Then, we tested a set of 48 compounds carefully selected to contain known in vivo genotoxins, nongenotoxins and drugs. Avoidance of irrelevant positives, a known issue with mammalian cell-based genotoxicity assays, is important to prevent early deselection of potentially promising compounds. Therefore, we enriched the validation set with compounds that were previously reported to produce irrelevant positive results in mammalian cell-based genotoxicity assays. The resulting dataset was used to set the relevant cut-off values for scoring a compound positive or negative, such that we obtained an optimal balance of high sensitivity (88%) and high specificity (87%). Finally, we tested an additional set of 16 drugs to further probe assay performance and 14 of them were classified correctly. To our knowledge, the present study is the most comprehensive validation of the in vitro flow cytometric micronucleus assay and the first to report parallel assessment with metabolic activation in reasonable throughput. The assay allows for rapidly screening novel compounds for genotoxicity and is therefore well-suited for use in early drug discovery projects. Environ.

  18. Pressure dependent stability and structure of carbon dioxide--a density functional study including long-range corrections.

    PubMed

    Gohr, Sebastian; Grimme, Stefan; Söhnel, Tilo; Paulus, Beate; Schwerdtfeger, Peter

    2013-11-01

    First-principles density functional theory (DFT) is used to study the solid-state modifications of carbon dioxide up to pressures of 60 GPa. All known molecular CO2 structures are investigated in this pressure range, as well as three non-molecular modifications. To account for long-range van der Waals interactions, the dispersion corrected DFT method developed by Grimme and co-workers (DFT-D3) is applied. We find that the DFT-D3 method substantially improves the results compared to the uncorrected DFT methods for the molecular carbon dioxide crystals. Enthalpies at 0 K and cohesive energies support only one possibility of the available experimental solutions for the structure of phase IV: the R3c modification, proposed by Datchi and co-workers [Phys. Rev. Lett. 103, 185701 (2009)]. Furthermore, comparing bulk moduli with experimental values, we cannot reproduce the quite large--rather typical for covalent crystal structures--experimental values for the molecular phases II and III. PMID:24206310

  19. Improvement of Surface Functionalities, Including Allergenicity Attenuation, of Whole Buckwheat Protein Fraction by Maillard-Type Glycation with Dextran

    PubMed Central

    Tazawa, Shigeru; Katayama, Shigeru; Hirabayashi, Masahiro; Yamaguchi, Daiki; Nakamura, Soichiro

    2014-01-01

    The purpose of the current study was to determine the effects of the introduction of polysaccharide chains onto the molecular surface of buckwheat proteins on buckwheat protein surface functionality. The whole buckwheat protein fraction (WBP) was prepared using 50 mM phosphate buffer (pH 7.5) containing 0.5 M NaCl and covalently linked with 6 kDa, 17.5 kDa, 40 kDa, 70 kDa, or 200 kDa dextran by Maillard-type glycation through controlled dry-heating at 60°C and 79% relative humidity for two weeks. Conjugation with 40 kDa dextran improved the water solubility and emulsifying properties of WBP without causing a serious loss of available lysine; 84.9% of the free amino groups were conserved. In addition, we found that the introduction of dextran chains onto the molecular surfaces of WBP attenuated the antigenicity of WBP. PMID:25580398

  20. Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

    PubMed Central

    2011-01-01

    Background Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care programs. Methods/Design This study will include an effect, process and cost evaluation using a mixed methods design of quantitative and qualitative methods. Three hospitals in the Netherlands with different levels of integrated geriatric health care will be evaluated using a quasi-experimental study design. Data collection on outcomes will take place through a prospective cohort study, which will incorporate a nested randomised controlled trial to evaluate the effects of a stay at the centre for prevention and reactivation for patients with complex problems. The study population will consist of elderly persons (65 years or older) at risk for functional loss who are admitted to one of the three hospitals. Data is prospectively collected at time of hospital admission (T0), three months (T1), and twelve months (T2) after hospital admission. Patient and informal caregiver outcomes (e.g. health related quality of life, activities of daily living, burden of care, (re-) admission in hospital or nursing homes, mortality) as well as process measures (e.g. the cooperation and collaboration of multidisciplinary teams, patient and informal caregiver satisfaction with care) will be measured. A qualitative analysis will determine the fidelity of intervention implementation as well as provide further context and explanation for quantitative outcomes. Finally, costs will be determined from a societal viewpoint to allow for cost effectiveness calculations. Discussion It is anticipated that higher levels of integrated hospital health care for at risk elderly will result in prevention of loss of functioning and loss of quality of life after

  1. Factors Affecting The Experimental Line Spread Function (Lsf) Measurement And Modulation Transfer Function (Mtf) Calculation Including Deviation In Characteristic Curve Shape

    NASA Astrophysics Data System (ADS)

    Dahle, Marcia E.; Haus, Arthur G.

    1980-08-01

    The major potential errors in the slit method measurement of the line spread function (LSF) and the modu-lation transfer function (MTF) of radiographic screen-film systems are reviewed. These errors are compared with the potential error introduced in the LSF due to an erroneous representation of the characteristic curve (sensitometric data). If a deviation in the sensitometric data results in a lower average gradient of the characteristic curve, the MTF will show higher resolution capabilities.

  2. Radiosurgery of functioning pituitary adenomas: Comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT

    SciTech Connect

    Grabenbauer, Gerhard G. . E-mail: gg@strahlen.imed.uni-erlangen.de; Ernst-Stecken, Antje; Schneider, Florian; Lambrecht, Ulrike; Ganslandt, Oliver

    2006-11-15

    Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA). Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8-10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: D{sub max} optic chiasm <8 Gy, Vol{sub 10Gy} temporal lobe <10 mL. End points: coverage, conformity index, homogeneity index (HI), Vol{sub 10Gy} temporal lobe. Results: For the end point 'improvement in coverage,' an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol{sub 10Gy} temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol{sub 10Gy} temporal lobe was <10 mL and D{sub max} optic chiasm <8 Gy. However, using circular collimators yielded the highest maximum dose with 39.8 Gy (HI, 2.2) as compared with 20.46-21.74 Gy (HI, 1.13-1.2) for other approaches. Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA.

  3. Acceleration of reverse analysis method using hyperbolic activation function

    NASA Astrophysics Data System (ADS)

    Pwasong, Augustine; Sathasivam, Saratha

    2015-10-01

    Hyperbolic activation function is examined for its ability to accelerate the performance of doing data mining by using a technique named as Reverse Analysis method. In this paper, we describe how Hopfield network perform better with hyperbolic activation function and able to induce logical rules from large database by using reverse analysis method: given the values of the connections of a network, we can hope to know what logical rules are entrenched in the database. We limit our analysis to Horn clauses.

  4. STUDENT ACTIVITIES STAFF FUNCTIONS--SUM AND SUBSTANCE.

    ERIC Educational Resources Information Center

    MARINE, JAMES

    THIS STUDY WAS DESIGNED TO ASSESS (1) THE CURRENT STATUS OF STUDENT ACTIVITIES (S.A.) WORK, (2) THE PERSONS ASSUMING MAJOR RESPONSIBILITY FOR THE S.A. FUNCTION AND THEIR CHARACTERISTICS, BACKGROUND, AND GOALS, (3) THE FUNCTIONS OF PERSONS WHO TAKE LEADERSHIP FOR S.A. PROGRAMS, AND (4) THE TRENDS AND DEVELOPMENTS IN S.A. COPIES OF A FIVE-PAGE…

  5. Sympathetic activation and nitric oxide function in early hypertension

    PubMed Central

    Okamoto, Luis E.; Diedrich, André; Choi, Leena; Robertson, David; Farley, Ginnie; Paranjape, Sachin; Biaggioni, Italo

    2012-01-01

    The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with Nω-monomethyl-l-arginine (l-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to l-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as “positive” controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, l-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study. PMID:22287587

  6. Description of excited states in [Re(Imidazole)(CO)3 (Phen)](+) including solvent and spin-orbit coupling effects: Density functional theory versus multiconfigurational wavefunction approach.

    PubMed

    Fumanal, Maria; Daniel, Chantal

    2016-10-15

    The low-lying electronic excited states of [Re(imidazole)(CO)3 (phen)](+) (phen = 1,10-phenanthroline) ranging between 420 nm and 330 nm have been calculated by means of relativistic spin-orbit time-dependent density functional theory (TD-DFT) and wavefunction approaches (state-average-CASSCF/CASPT2). A direct comparison between the theoretical absorption spectra obtained with different methods including SOC and solvent corrections for water points to the difficulties at describing on the same footing the bands generated by metal-to-ligand charge transfer (MLCT), intraligand (IL) transition, and ligand-to-Ligand- charge transfer (LLCT). While TD-DFT and three-roots-state-average CASSCF (10,10) reproduce rather well the lowest broad MLCT band observed in the experimental spectrum between 420 nm and 330 nm, more flexible wavefunctions enlarged either by the number of roots or by the number of active orbitals and electrons destabilize the MLCT states by introducing IL and LLCT character in the lowest part of the absorption spectrum. © 2016 Wiley Periodicals, Inc. PMID:27510636

  7. Description of excited states in [Re(Imidazole)(CO)3 (Phen)](+) including solvent and spin-orbit coupling effects: Density functional theory versus multiconfigurational wavefunction approach.

    PubMed

    Fumanal, Maria; Daniel, Chantal

    2016-10-15

    The low-lying electronic excited states of [Re(imidazole)(CO)3 (phen)](+) (phen = 1,10-phenanthroline) ranging between 420 nm and 330 nm have been calculated by means of relativistic spin-orbit time-dependent density functional theory (TD-DFT) and wavefunction approaches (state-average-CASSCF/CASPT2). A direct comparison between the theoretical absorption spectra obtained with different methods including SOC and solvent corrections for water points to the difficulties at describing on the same footing the bands generated by metal-to-ligand charge transfer (MLCT), intraligand (IL) transition, and ligand-to-Ligand- charge transfer (LLCT). While TD-DFT and three-roots-state-average CASSCF (10,10) reproduce rather well the lowest broad MLCT band observed in the experimental spectrum between 420 nm and 330 nm, more flexible wavefunctions enlarged either by the number of roots or by the number of active orbitals and electrons destabilize the MLCT states by introducing IL and LLCT character in the lowest part of the absorption spectrum. © 2016 Wiley Periodicals, Inc.

  8. Effects of Physical (In)activity on Platelet Function

    PubMed Central

    Heber, Stefan; Volf, Ivo

    2015-01-01

    As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality. PMID:26557653

  9. High water-stressed population estimated by world water resources assessment including human activities under SRES scenarios

    NASA Astrophysics Data System (ADS)

    Kiguchi, M.; Shen, Y.; Kanae, S.; Oki, T.

    2009-04-01

    In an argument of the reduction and the adaptation for the climate change, the evaluation of the influence by the climate change is important. When we argue in adaptation plan from a damage scale and balance with the cost, it is particularly important. Parry et al (2001) evaluated the risks in shortage of water, malaria, food, the risk of the coast flood by temperature function and clarified the level of critical climate change. According to their evaluation, the population to be affected by the shortage of water suddenly increases in the range where temperature increases from 1.5 to 2.0 degree in 2080s. They showed how much we need to reduce emissions in order to draw-down significantly the number at risk. This evaluation of critical climate change threats and targets of water shortage did not include the water withdrawal divided by water availability. Shen et al (2008a) estimated the water withdrawal of projection of future world water resources according to socio-economic driving factors predicted for scenarios A1b, A2, B1, and B2 of the Special Report on Emission Scenarios (SRES). However, these results were in function of not temperature but time. The assessment of the highly water-stressed population considered the socioeconomic development is necessary for a function of the temperature. Because of it is easy to understand to need to reduce emission. We present a multi-GCM analysis of the global and regional populations lived in highly water-stressed basin for a function of the temperature using the socioeconomic data and the outputs of GCMs. In scenario A2, the population increases gradually with warming. On the other hand, the future projection population in scenario A1b and B1 increase gradually until the temperature anomaly exceeds around from +1 to +1.5 degree. After that the population is almost constant. From Shen et al (2008b), we evaluated the HWSP and its ratio in the world with temperature function for scenarios A1B, A2, and B1 by the index of W

  10. Sexual Function, Activity, and Satisfaction among Women Receiving Maintenance Hemodialysis

    PubMed Central

    Mor, Maria K.; Sevick, Mary Ann; Shields, Anne Marie; Green, Jamie A.; Palevsky, Paul M.; Arnold, Robert M.; Fine, Michael J.

    2014-01-01

    Summary Background and objectives Past studies that demonstrated that sexual dysfunction is common among women receiving chronic hemodialysis did not distinguish sexual dysfunction/difficulty from sexual inactivity. This study sought to differentiate these in order to elucidate the prevalence of true “sexual dysfunction” in this population. Design, setting, participants, & measurements As part of a clinical trial of symptom management strategies in patients receiving chronic hemodialysis, female sexual function was prospectively assessed monthly for 6 months and quarterly thereafter using the Female Sexual Function Index, to which questions were added differentiating sexual dysfunction/difficulty from sexual inactivity. Beginning in month 7, patients were asked three questions about sexual activity, difficulty, and satisfaction monthly. Results Of the women enrolled in the clinical trial,125 participants completed 1721 assessments between 2009 and 2011. Scores on 574 of 643 (89%) quarterly Female Sexual Function Index assessments were consistent with sexual dysfunction, due largely to sexual inactivity, which was reported on 525 (82%) quarterly assessments. When reported (n=1663), the most frequently described reasons for sexual inactivity were lack of interest in sex (n=715; 43%) and lack of a partner (n=647; 39%), but rarely sexual difficulty (n=36; 2%). When reported (n=1582), women were moderately to very satisfied with their sexual life on 1020 (64%) assessments and on 513 of 671 (76%) assessments in which lack of interest was cited as a reason for sexual inactivity. Women indicated an interest in learning about the causes of and treatment for sexual dysfunction on just 5% of all assessments. Conclusions Although many women receiving chronic hemodialysis are sexually inactive, few describe sexual difficulty. Most, including those with a lack of interest in sex, are satisfied with their sexual life and few wish to learn about treatment options. These

  11. Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-, sleep-, and sleep-related diseases including obstructive sleep apnea.

    PubMed

    Dergacheva, Olga; Weigand, Letitia A; Dyavanapalli, Jhansi; Mares, Jacquelyn; Wang, Xin; Mendelowitz, David

    2014-01-01

    Parasympathetic cardiac vagal neurons (CVNs) in the brainstem dominate the control of heart rate. Previous work has determined that these neurons are inherently silent, and their activity is largely determined by synaptic inputs to CVNs that include four major types of synapses that release glutamate, GABA, glycine, or serotonin. Whereas prior reviews have focused on glutamatergic, GABAergic and glycinergic pathways, and the receptors in CVNs activated by these neurotransmitters, this review focuses on the alterations in CVN activity with hypoxia-, sleep-, and sleep-related cardiovascular diseases including obstructive sleep apnea.

  12. [Evaluation of an obesity prevention intervention which included nutrition education and physical activity applied in public schools of Santiago, Chile].

    PubMed

    Kain, Juliana; Leyton, Bárbara; Concha, Fernando; Weisstaub, Gerardo; Lobos, Luz; Bustos, Nelly; Vio, Fernando

    2012-03-01

    The main objective of this study was to assess the effectiveness of an obesity prevention intervention which included nutrition education and physical activity applied to low income Chilean children in a longitudinal three-year follow-up study. Participants included all 4-7 year old children from 7 public schools located in a low socioeconomic district of Santiago. The main aspects of the intervention were: training of teachers so they could apply an educational program on healthy eating, increase in physical education classes from 3 to 4 per week, and improvement of their quality. Weight, height, waist circumference (WC) and the 6-minute walk distance (6MWD) were assessed yearly in 597 children. We calculated BMI, BMI Z, % normal (N), overweight (OW) and obesity (OB), WC > 90th percentile (NHANES III) and fitness (6MWD/height). Annual changes in BMI Z, WC, 6MWD and fitness were assessed, using repeated measures ANOVA and the test of proportions. Knowledge in healthy eating was assessed during 2 of the 3 years. Results showed that % OB remained unchanged for 2 years (17%) but increased to 19.3% at follow-up. BMI Z increased from 0.3 to 0.38 (p = 0.052) in the N, remained unchanged in the OW, while decreasing significantly in the OB (2.73 to 2.41 p < 0.0001). % WC > 90 th percentile decreased in the OW and OB; 6 MWD was higher in the OW, but the increase in distance overtime was greater among the N. Overall fitness improved, however it was only significant among the N (p = 0.0002). There was a significant increase in food knowledge. We conclude that in spite of a decrease in BMI Z of the OB, an improvement in fitness in the N and food knowledge in all the children, obesity increased at follow-up. This study shows that in school-based obesity programs it is necessary to apply more intense interventions with another type of methodology; otherwise this condition will continue to rise.

  13. AMP-ACTIVATED PROTEIN KINASE ACTIVATION AS A STRATEGY FOR PROTECTING VASCULAR ENDOTHELIAL FUNCTION

    PubMed Central

    Zou, Ming-Hui; Wu, Yong

    2010-01-01

    SUMMARY 1. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase involved in the regulation of cellular and organismal metabolism. AMPK has a heterotrimeric structure, consisting of a catalytic α-subunit and regulatory β- and γ-subunits, each of which has two or more isoforms that are differentially expressed in various tissues and that arise from distinct genes. The AMPK system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. In addition, AMPK is activated by physiological stimuli and oxidants. 2. The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK. As a consequence, AMPK has been proposed as a candidate target for therapeutic intervention in the treatment of both Type 2 diabetes and metabolic syndrome owing to its central role in the regulation of energy balance; it may also have a role in weight control. 3. In the present brief review, we summarize the recent progress of AMPK signalling and regulation focusing on vascular endothelial cells. We further hypothesize that AMPK is a dual sensor for energy and redox status within a cell and AMPK may be a therapeutic target for protecting vascular endothelial function. PMID:18177481

  14. Feelings of well being in elderly people: relationship to physical activity and physical function.

    PubMed

    Garatachea, Nuria; Molinero, Olga; Martínez-García, Raquel; Jiménez-Jiménez, Rodrigo; González-Gallego, Javier; Márquez, Sara

    2009-01-01

    The aim of the research was to investigate in a sample of Spanish elderly whether measures of physical activity and physical function are related to feelings of well being, and whether level of dependence is a moderator in the relation of well being, physical activity and physical function. The sample was a cohort of 151 elderly people (89 women and 62 men, aged 60-98 years) from the North of Spain. Participants completed surveys including demographic characteristics, and measures of physical activity (Yale Physical Activity Survey, YPAS), instrumental activities of daily living (Barthel Index, BI) and well being (Psychological Well Being Scale, from Spanish: Escala de Bienestar Psicológico=EBP). Components of the physical function were measured by the Senior Fitness Test (SFT). Upper and lower body strength, dynamic balance, aerobic endurance, self-reported weekly energy expenditure and physical activity total time were significantly correlated with both Material and Subjective well being. All components of physical function were significantly impaired in dependent subjects when compared to independent individuals of the same sex and physical activity category. Significant differences were also observed in Subjective well being among less active dependent or independent individuals. In conclusion, physical function and physical activity are related to feelings of well being, and results emphasize the positive functional and psychological effects of physical activity in dependent subjects.

  15. Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge.

    PubMed

    Tara, S; Elcock, A H; Kirchhoff, P D; Briggs, J M; Radic, Z; Taylor, P; McCammon, J A

    1998-12-01

    It is known that anionic surface residues play a role in the long-range electrostatic attraction between acetylcholinesterase and cationic ligands. In our current investigation, we show that anionic residues also play an important role in the behavior of the ligand within the active site gorge of acetylcholinesterase. Negatively charged residues near the gorge opening not only attract positively charged ligands from solution to the enzyme, but can also restrict the motion of the ligand once it is inside of the gorge. We use Brownian dynamics techniques to calculate the rate constant kon, for wild type and mutant acetylcholinesterase with a positively charged ligand. These calculations are performed by allowing the ligand to diffuse within the active site gorge. This is an extension of previously reported work in which a ligand was allowed to diffuse only to the enzyme surface. By setting the reaction criteria for the ligand closer to the active site, better agreement with experimental data is obtained. Although a number of residues influence the movement of the ligand within the gorge, Asp74 is shown to play a particularly important role in this function. Asp74 traps the ligand within the gorge, and in this way helps to ensure a reaction.

  16. Ultrananocrystalline diamond thin films functionalized with therapeutically active collagen networks.

    SciTech Connect

    Huang, H.; Chen, M.; Bruno, P.; Lam, R.; Robinson, E.; Gruen, D.; Ho, D.; Materials Science Division; Northwestern Univ.

    2009-01-01

    The fabrication of biologically amenable interfaces in medicine bridges translational technologies with their surrounding biological environment. Functionalized nanomaterials catalyze this coalescence through the creation of biomimetic and active substrates upon which a spectrum of therapeutic elements can be delivered to adherent cells to address biomolecular processes in cancer, inflammation, etc. Here, we demonstrate the robust functionalization of ultrananocrystalline diamond (UNCD) with type I collagen and dexamethasone (Dex), an anti-inflammatory drug, to fabricate a hybrid therapeutically active substrate for localized drug delivery. UNCD oxidation coupled with a pH-mediated collagen adsorption process generated a comprehensive interface between the two materials, and subsequent Dex integration, activity, and elution were confirmed through inflammatory gene expression assays. These studies confer a translational relevance to the biofunctionalized UNCD in its role as an active therapeutic network for potent regulation of cellular activity toward applications in nanomedicine.

  17. Geometrical modulation transfer function for different pixel active area shapes

    NASA Astrophysics Data System (ADS)

    Yadid-Pecht, Orly

    2000-04-01

    In this work we consider the effect of the pixel active area geometrical shape on the modulation transfer function (MTF) of an image sensor. When designing a CMOS Active Pixel Sensor, or a CCD or CID sensor for this matter, the active area of the pixel would have a certain geometrical shape which might not cover the whole pixel area. To improve the device performance, it is important to understand the effect this has on the pixel sensitivity and on the resulting MTF. We perform a theoretical analysis of the MTF for the active area shape and derive explicit formulas for the transfer function for pixel arrays with a square, a rectangular and an L shaped active area (most commonly used), and generalize for any connected active area shape. Preliminary experimental results of subpixel scanning sensitivity maps and the corresponding MTFs have also bee obtained, which confirm the theoretical derivations. Both the simulation results and the MTF calculated from the point spread function measurements of the actual pixel arrays show that the active area shape contributes significantly to the behavior of the overall MTF. The results also indicate that for any potential pixel active area shape, the effect of its diversion from the square pixel could be calculated, so that tradeoff between the conflicting requirements, such as SNR and MTF, could be compared per each pixel design for better overall sensor performance.

  18. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails § 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  19. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails § 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  20. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails § 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  1. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails § 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  2. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails § 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  3. HEPS Inventory Tool: An Inventory Tool Including Quality Assessment of School Interventions on Healthy Eating and Physical Activity

    ERIC Educational Resources Information Center

    Dadaczynski, Kevin; Paulus, Peter; de Vries, Nanne; de Ruiter, Silvia; Buijs, Goof

    2010-01-01

    The HEPS Inventory Tool aims to support stakeholders working in school health promotion to promote high quality interventions on healthy eating and physical activity. As a tool it provides a step-by-step approach on how to develop a national or regional inventory of existing school based interventions on healthy eating and physical activity. It…

  4. Swell activated chloride channel function in human neutrophils

    SciTech Connect

    Salmon, Michael D.; Ahluwalia, Jatinder

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  5. Functional implications on the mechanism of the function of photosystem II including water oxidation based on the structure of photosystem II.

    PubMed Central

    Fromme, Petra; Kern, Jan; Loll, Bernhard; Biesiadka, Jaceck; Saenger, Wolfram; Witt, Horst T; Krauss, Norbert; Zouni, Athina

    2002-01-01

    The structure of photosystem I at 3.8 A resolution illustrated the main structural elements of the water-oxidizing photosystem II complex, including the constituents of the electron transport chain. The location of the Mn cluster within the complex has been identified for the first time to our knowledge. At this resolution, no individual atoms are visible, however, the electron density of the Mn cluster can be used to discuss both the present models of the Mn cluster as revealed from various spectroscopic methods and the implications for the mechanisms of water oxidation. Twenty-six chlorophylls from the antenna system of photosystem II have been identified. They are arranged in two layers, one close to the stromal side and one close to the lumenal side. Comparing the structure of the antenna system of photosystem II with the chlorophyll arrangement in photosystem I, which was recently determined at 2.5 A resolution shows that photosystem II lacks the central domain of the photosystem I antenna, which is discussed in respect of the repair cycle of photosystem II due to photoinhibition. PMID:12437872

  6. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging.

    PubMed

    Umanskaya, Alisa; Santulli, Gaetano; Xie, Wenjun; Andersson, Daniel C; Reiken, Steven R; Marks, Andrew R

    2014-10-21

    Age-related skeletal muscle dysfunction is a leading cause of morbidity that affects up to half the population aged 80 or greater. Here we tested the effects of increased mitochondrial antioxidant activity on age-dependent skeletal muscle dysfunction using transgenic mice with targeted overexpression of the human catalase gene to mitochondria (MCat mice). Aged MCat mice exhibited improved voluntary exercise, increased skeletal muscle specific force and tetanic Ca(2+) transients, decreased intracellular Ca(2+) leak and increased sarcoplasmic reticulum (SR) Ca(2+) load compared with age-matched wild type (WT) littermates. Furthermore, ryanodine receptor 1 (the sarcoplasmic reticulum Ca(2+) release channel required for skeletal muscle contraction; RyR1) from aged MCat mice was less oxidized, depleted of the channel stabilizing subunit, calstabin1, and displayed increased single channel open probability (Po). Overall, these data indicate a direct role for mitochondrial free radicals in promoting the pathological intracellular Ca(2+) leak that underlies age-dependent loss of skeletal muscle function. This study harbors implications for the development of novel therapeutic strategies, including mitochondria-targeted antioxidants for treatment of mitochondrial myopathies and other healthspan-limiting disorders. PMID:25288763

  7. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    PubMed

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  8. Mastering tricyclic ring systems for desirable functional cannabinoid activity

    PubMed Central

    Petrov, Ravil R.; Knight, Lindsay; Chen, Shao-Rui; Wager-Miller, Jim; McDaniel, Steven W.; Diaz, Fanny; Barth, Francis; Pan, Hui-Lin; Mackie, Ken; Cavasotto, Claudio N.; Diaz, Philippe

    2013-01-01

    There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain and other indications. In continuation of our ongoing program aiming for the development of new small molecule cannabinoid ligands, we have synthesized a novel series of carbazole and γ-carboline derivatives. The affinities of the newly synthesized compounds were determined by a competitive radioligand displacement assay for human CB2 cannabinoid receptor and rat CB1 cannabinoid receptor. Functional activity and selectivity at human CB1 and CB2 receptors were characterized using receptor internalization and [35S]GTP-γ-S assays. The structure-activity relationship and optimization studies of the carbazole series have led to the discovery of a non-selective CB1 and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2 selectivity of this lead compound have led to the discovery of CB2 selective compound 64, which robustly internalized CB2 receptors. Compound 64 had potent inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain. Other potent and CB2 receptor–selective compounds, including compounds 63 and 68, and a selective CB1 agonist, compound 74 were also discovered. In addition, we identified the CB2 ligand 35 which failed to promote CB2 receptor internalization and inhibited compound CP55,940-induced CB2 internalization despite a high CB2 receptor affinity. The present study provides novel tricyclic series as a starting point for further investigations of CB2 pharmacology and pain treatment. PMID:24125850

  9. Informational Complexity and Functional Activity of RNA Structures

    PubMed Central

    Carothers, James M.; Oestreich, Stephanie C.; Davis, Jonathan H.

    2004-01-01

    Very little is known about the distribution of functional DNA, RNA, and protein molecules in sequence space. The question of how the number and complexity of distinct solutions to a particular biochemical problem varies with activity is an important aspect of this general problem. Here we present a comparison of the structures and activities of eleven distinct GTP-binding RNAs (aptamers). By experimentally measuring the amount of information required to specify each optimal binding structure, we show that defining a structure capable of 10-fold tighter binding requires approximately 10 additional bits of information. This increase in information content is equivalent to specifying the identity of five additional nucleotide positions and corresponds to an ∼1000-fold decrease in abundance in a sample of random sequences. We observe a similar relationship between structural complexity and activity in a comparison of two catalytic RNAs (ribozyme ligases), raising the possibility of a general relationship between the complexity of RNA structures and their functional activity. Describing how information varies with activity in other heteropolymers, both biological and synthetic, may lead to an objective means of comparing their functional properties. This approach could be useful in predicting the functional utility of novel heteropolymers. PMID:15099096

  10. Using function-focused care to increase physical activity among older adults.

    PubMed

    Resnick, Barbara; Galik, Elizabeth

    2013-01-01

    Despite the known benefits of physical activity for older adults, adherence to regular physical activity recommendations is poor. Less than half of adults in this country meet physical activity recommendations with reasons for lack of adherence including such things as access, motivation, pain, fear, comorbidities, among others. To overcome these challenges, function-focused care was developed. Function-focused care is a philosophy of care that focuses on evaluating the older adult's underlying capability with regard to function and physical activity and helping him or her optimize and maintain physical function and ability and continually increase time spent in physical activity. Examples of function-focused care include such things as using verbal cues during bathing, so the older individual performs the tasks rather than the caregiver bathing the individual; walking a resident or patient to the bathroom rather than using a urinal, or taking a resident to an exercise class. There are now over 20 studies supporting the benefits of function-focused care approaches across all settings and different types of patient groups (i.e, those with mild versus moderate-to-severe cognitive impairment). The approaches for implementation of function-focused care have also been well supported and have moved beyond establishing effectiveness to considering dissemination and implementation of this approach into real world clinical settings. The process of dissemination and implementation has likewise been articulated and supported, and ongoing work needs to continue in this venue across all care settings. PMID:24894140

  11. Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition

    PubMed Central

    Pu, Weidan; Rolls, Edmund T.; Guo, Shuixia; Liu, Haihong; Yu, Yun; Xue, Zhimin; Feng, Jianfeng; Liu, Zhening

    2014-01-01

    In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity. PMID:25389520

  12. Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition.

    PubMed

    Pu, Weidan; Rolls, Edmund T; Guo, Shuixia; Liu, Haihong; Yu, Yun; Xue, Zhimin; Feng, Jianfeng; Liu, Zhening

    2014-01-01

    In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity.

  13. Neural progenitor cells regulate microglia functions and activity.

    PubMed

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  14. Functional modifications of macrophage activity after sublethal irradiation. [Toxoplasma gondii

    SciTech Connect

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin.

  15. 14 CFR 440.11 - Duration of coverage for licensed launch, including suborbital launch, or permitted activities...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... LICENSING FINANCIAL RESPONSIBILITY Financial Responsibility for Licensed and Permitted Activities § 440.11...; modifications. (a) Insurance coverage required under § 440.9, or other form of financial responsibility, shall... recovery; or (ii) The FAA's determination that risk to third parties and Government property as a result...

  16. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

    PubMed

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-07-02

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  17. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  18. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

  19. [Significance of the functional activity of antibodies in influenza immunity].

    PubMed

    Naĭkhin, A N; Artem'eva, S A; Bosak, L V; Katorgina, L G

    1995-01-01

    A simple and inexpensive test for mass examination of the functional activity of serum antibodies was developed. The test is based on a kinetic serologic reaction that reflects the time course of changes in antibody titers depending on the time of contact of the tested material with antigen. The curves of serum kinetic titration were processed on a computer by the special programme. As a result, an integral factor, an antibody functional activity index (AFAI) was calculated for each serum sample under study. The titers and AFAI were determined in more than 2,000 healthy persons, patients with influenza A and B, and those immunized with different influenza vaccines. The persons having similar antibody titers were demonstrated to greatly differ in AFAI. The functional activity of antibodies is a more precise marker of protection from influenza than the routine quantitative characteristics of antibodies, i.e. titers. The high baseline AFAI decreased the severity of influenza infection. Live influenza vaccines stimulated the production of antibodies having higher AFAI than inactivated ones. The live influenza strains (candidates for vaccine ones) significantly differed in their ability to stimulate the production of antibodies having a high functional activity.

  20. A Comparison of Brunt Criteria, the Non Alcoholic Fatty Liver Disease Activity Score (NAS) & a Proposed NAS-including fibrosis as Valid Diagnostic Scores for NASH

    PubMed Central

    Santiago-Rolón, Amarilys; Purcell, Dagmary; Rosado, Kathia; Toro, Doris H.

    2016-01-01

    Objective Non-alcoholic steatohepatitis (NASH) can result in cirrhosis and end stage liver disease. It is of utmost importance to differentiate NASH from simple steatosis. The aim of this study is to determine the prevalence of NASH in Latino veterans with metabolic syndrome and compare histologic grading using Brunt Criteria, the NAFLD activity score (NAS), and a proposed NAS score including fibrosis. Methods Veterans with metabolic syndrome, hepatic steatosis and elevation of ALT/AST who underwent a liver biopsy from 2004-2010 were included in this study. Biopsies were evaluated by a single blinded Hepatopathologist. Steatosis, lobular inflammation, ballooning and fibrosis were graded per specimen. Each biopsy was evaluated using Brunt criteria, NAS and NAS plus fibrosis. Results Sixty patients were included in this study, 88.3% men with a mean age of 50.4 (± 12.8). 50.0% met criteria for NASH according to the Brunt system. When classifying biopsies using NAS, only 30.0% (18/60) had a score ≥5, while when adding fibrosis, the number of patients with a score ≥5 increased to 33 (55.0%). When evaluating the predictive ability of the two scoring systems, we found that NAS including fibrosis had a higher sensitivity than NAS (86.7% vs. 40.0%) and a lower specificity (76.7% vs. 80.0%). Conclusion In our population with metabolic syndrome and altered liver function tests, about 50-55% had steatohepatitis. There were significant differences between the scoring systems. When using NAS-plus-fibrosis more patients were recognized and the sensitivity increased. Further validation studies are required to evaluate this proposed NAS scoring System. PMID:26602577

  1. Heated Proteins are Still Active in a Functionalized Nanoporous Support

    SciTech Connect

    Chen, Baowei; Qi, Wen N.; Li, Xiaolin; Lei, Chenghong; Liu, Jun

    2013-07-08

    We report that even under the heated condition, the conformation and activity of a protein can be hoarded in a functionalized nanoporous support via non-covalent interaction, although the hoarded protein was not exhibiting the full protein activity, the protein released subsequently still maintained its native conformation and activity. Glucose oxidase (GOX) was spontaneously and largely entrapped in aminopropyl-functionalized mesoporous silica (NH2-FMS) at 20 oC via a dominant electrostatic interaction. Although FMS-GOX displayed 45% activity of the free enzyme in solution, the GOX released from FMS exhibited its 100% activity prior to the entrapment. Surprisingly, the released GOX from FMS still maintained 89% of its initial activity prior to the entrapment after FMS-GOX was incubated at 60 oC for 1 h prior to release, while the free GOX in solution lost nearly all activity under the same incubation. Intrinsic fluorescence emission of GOX and native electrophoresis demonstrated that the heating resulted in significant conformational changes and oligomeric structures of the free GOX, but FMS efficiently maintained the thermal stability of GOX therein and resisted the thermal denaturation and oligomeric aggregation.

  2. Weight management including dietary and physical activity advice provided by Australian physiotherapists: a pilot cross-sectional survey.

    PubMed

    Snodgrass, Suzanne J; Carter, Amy E; Guest, Maya; Collins, Clare E; James, Carole; Kable, Ashley K; Ashby, Samantha E; Plotnikoff, Ronald C

    2014-08-01

    Physiotherapists may have an impact on obesity prevention and treatment by providing nutrition and physical activity advice to overweight or obese clients; yet little is known about physiotherapists' beliefs and practices related to client weight management. The aim of this pilot study was to determine the practices, beliefs, attitudes and knowledge of physiotherapists regarding the provision of weight management advice to overweight or obese clients. Physiotherapists (n = 65) working in multiple practice settings completed a self-administered questionnaire. Logistic regression determined factors associated with the provision of dietary and physical activity advice for weight management. The majority of physiotherapists (n = 53 [81.5%]) believed providing weight management advice was within their scope of practice, yet only a minority had received training during their professional entry level education (n = 13 [20%]) or through professional development (n = 7 [11%]). Most physiotherapists (n = 55 [84.6%]) provided physical activity advice for weight management, but a minority (n = 27 [41.5%]) provided dietary advice. Having received training in weight management during their professional entry level education was associated with providing dietary advice (Odds ratio 8.8, 95% confidence interval 2.0-38.9, p = 0.004). Training in weight management may increase the likelihood of physiotherapists providing dietary advice, improving physiotherapists' management of obesity.

  3. The IKAROS Interaction with a Complex Including Chromatin Remodeling and Transcription Elongation Activities Is Required for Hematopoiesis

    PubMed Central

    Bottardi, Stefania; Mavoungou, Lionel; Pak, Helen; Daou, Salima; Bourgoin, Vincent; Lakehal, Yahia A.; Affar, El Bachir; Milot, Eric

    2014-01-01

    IKAROS is a critical regulator of hematopoietic cell fate and its dynamic expression pattern is required for proper hematopoiesis. In collaboration with the Nucleosome Remodeling and Deacetylase (NuRD) complex, it promotes gene repression and activation. It remains to be clarified how IKAROS can support transcription activation while being associated with the HDAC-containing complex NuRD. IKAROS also binds to the Positive-Transcription Elongation Factor b (P-TEFb) at gene promoters. Here, we demonstrate that NuRD and P-TEFb are assembled in a complex that can be recruited to specific genes by IKAROS. The expression level of IKAROS influences the recruitment of the NuRD-P-TEFb complex to gene regulatory regions and facilitates transcription elongation by transferring the Protein Phosphatase 1α (PP1α), an IKAROS-binding protein and P-TEFb activator, to CDK9. We show that an IKAROS mutant that is unable to bind PP1α cannot sustain gene expression and impedes normal differentiation of IkNULL hematopoietic progenitors. Finally, the knock-down of the NuRD subunit Mi2 reveals that the occupancy of the NuRD complex at transcribed regions of genes favors the relief of POL II promoter-proximal pausing and thereby, promotes transcription elongation. PMID:25474253

  4. Functional constituents of the active site of human neutrophil collagenase.

    PubMed

    Mookhtiar, K A; Wang, F; Van Wart, H E

    1986-05-01

    A series of chemical modification reactions has been carried out to identify functional constituents of the active site of human neutrophil collagenase. The enzyme is reversibly inhibited by the transition metal chelating agent 1,10-phenanthroline, and inhibition is fully reversed by zinc. Removal of weakly bound metal ions by gel filtration inactivates collagenase, and activity is fully restored on immediate readdition of calcium. The enzyme is unaffected by reagents that modify serine, cysteine, and arginine residues. However, reaction with the carboxyl reagents cyclohexylmorpholinocarbodiimide and Woodward's Reagent K lowers the activity of the enzyme substantially. Acetylimidazole inactivates the enzyme, but activity is completely restored on addition of hydroxylamine. The enzyme is also inactivated by tetranitromethane, indicating that it contains an essential tyrosine residue. Acylation of collagenase with diethyl pyrocarbonate, diketene, acetic anhydride, or trinitrobenzenesulfonate inactivates the enzyme, and activity is not restored on addition of hydroxylamine, indicating the presence of an essential lysine residue.

  5. Simultaneous BVI noise and vibration reduction in rotorcraft using actively-controlled flaps and including performance considerations

    NASA Astrophysics Data System (ADS)

    Patt, Daniel A.

    This work presents the development and application of an active control approach for reduction of both vibration and noise induced by helicopter rotor blade vortex interaction (BVI). Control is implemented through single or dual actively controlled flaps (ACFs) on each blade. Low-speed helicopter flight is prone to severe BVI, resulting in elevated vibration and noise levels. Existing research has suggested that when some form of active control is used to reduce vibration, noise will increase and vice versa. The present research achieves simultaneous reduction of noise and vibration, and also investigates the physical sources of the observed reduction. The initial portion of this work focused on developing a tool for simulating helicopter noise and vibrations in the BVI flight regime. A method for predicting compressible unsteady blade surface pressure distribution on rotor blades was developed and combined with an enhanced free-wake model and an acoustic prediction tool with provisions for blade flexibility. These elements were incorporated within an aeroelastic analysis featuring fully coupled flap-lag-torsional blade dynamics. Subsequently, control algorithms were developed that were effective for reducing noise and vibration even in the nonlinear BVI flight regime; saturation limits were incorporated constraining flap deflections to specified limits. The resulting simulation was also validated with a wide range of experimental data, achieving excellent correlation. Finally, a number of active control studies were performed. Multi-component vibration reductions of 40--80% could be achieved, while incurring a small noise penalty. Noise was reduced using an onboard feedback microphone; reductions of 4--10 dB on the advancing side were observed on a plane beneath the rotor when using dual flaps. Finally, simultaneous noise and vibration reduction was studied. A reduction of about 5 dB in noise on the advancing side combined with a 60% reduction in vibration was

  6. Angiotensin-converting enzyme 2 activation improves endothelial function.

    PubMed

    Fraga-Silva, Rodrigo A; Costa-Fraga, Fabiana P; Murça, Tatiane M; Moraes, Patrícia L; Martins Lima, Augusto; Lautner, Roberto Q; Castro, Carlos H; Soares, Célia Maria A; Borges, Clayton L; Nadu, Ana Paula; Oliveira, Marilene L; Shenoy, Vinayak; Katovich, Michael J; Santos, Robson A S; Raizada, Mohan K; Ferreira, Anderson J

    2013-06-01

    Diminished release and function of endothelium-derived nitric oxide coupled with increases in reactive oxygen species production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin-angiotensin system composed by angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic angiotensin-converting enzyme 2 would improve endothelial function by decreasing the reactive oxygen species production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule angiotensin-converting enzyme 2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1 mg/kg per day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1-7), and it was reduced in Mas knockout mice. These effects were associated with reduction in reactive oxygen species production. In addition, Ang II-induced reactive oxygen species production in human aortic endothelial cells was attenuated by preincubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that angiotensin-converting enzyme 2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease.

  7. Association between Cerebral Amyloid Deposition and Clinical Factors Including Cognitive Function in Geriatric Depression: Pilot Study Using Amyloid Positron Emission Tomography

    PubMed Central

    Kim, Hye-Geum; Kong, Eun-Jung; Cheon, Eun-Jin; Kim, Hae-Won; Koo, Bon-Hoon

    2016-01-01

    The purpose of this study was to explore the relationship between cerebral amyloid deposition and overall clinical factors including cognitive functions in geriatric depression by using 18F-florbetaben positron emission tomography. Thirteen subjects aged over 60 years who had a history of major depressive disorder and also had subjective memory complaint were included. Of all subjects, 3 subjects judged as amyloid positive, and the others judged as amyloid negative. Their memory, visuospatial functions and attention abilities were negatively correlated with amyloid deposition in specific brain regions, but their language and recognition abilities were not correlated with any region. The amyloid deposition of the whole brain region was significantly negatively correlated with immediate memory. PMID:27776391

  8. The Influence of Organized Physical Activity (including Gymnastics) on Young Adult Skeletal Traits: Is Maturity Phase Important?

    PubMed Central

    Bernardoni, Brittney; Scerpella, Tamara A.; Rosenbaum, Paula F.; Kanaley, Jill A.; Raab, Lindsay N.; Li, Quefeng; Wang, Sijian; Dowthwaite, Jodi N.

    2015-01-01

    We prospectively evaluated adolescent organized physical activity (PA) as a factor in adult female bone traits. Annual DXA scans accompanied semi-annual records of anthropometry, maturity and PA for 42 participants in this preliminary analysis (criteria: appropriately timed DXA scans at ~1 year pre-menarche [predictor] and ~5 years post-menarche [dependent variable]). Regression analysis evaluated total adolescent inter-scan PA and PA over 3 maturity sub-phases as predictors of young adult bone outcomes: 1) bone mineral content (BMC), geometry and strength indices at non-dominant distal radius and femoral neck; 2) sub-head BMC; 3) lumbar spine BMC. Analyses accounted for baseline gynecological age (years pre- or post-menarche), baseline bone status, adult body size and inter-scan body size change. Gymnastics training was evaluated as a potentially independent predictor, but did not improve models for any outcomes (p<0.07). Pre-menarcheal bone traits were strong predictors of most adult outcomes (semi-partial r2 = 0.21-0.59, p≤0.001). Adult 1/3 radius and sub-head BMC were predicted by both total PA and PA 1-3 years post-menarche (p<0.03). PA 3-5 years post-menarche predicted femoral narrow neck width, endosteal diameter and buckling ratio (p<0.05). Thus, participation in organized physical activity programs throughout middle and high school may reduce lifetime fracture risk in females. PMID:25386845

  9. The Influence of Organized Physical Activity (Including Gymnastics) on Young Adult Skeletal Traits: Is Maturity Phase Important?

    PubMed

    Bernardoni, Brittney; Scerpella, Tamara A; Rosenbaum, Paula F; Kanaley, Jill A; Raab, Lindsay N; Li, Quefeng; Wang, Sijian; Dowthwaite, Jodi N

    2015-05-01

    We prospectively evaluated adolescent organized physical activity (PA) as a factor in adult female bone traits. Annual DXA scans accompanied semiannual records of anthropometry, maturity, and PA for 42 participants in this preliminary analysis (criteria: appropriately timed DXA scans at ~1 year premenarche [predictor] and ~5 years postmenarche [dependent variable]). Regression analysis evaluated total adolescent interscan PA and PA over 3 maturity subphases as predictors of young adult bone outcomes: 1) bone mineral content (BMC), geometry, and strength indices at nondominant distal radius and femoral neck; 2) subhead BMC; 3) lumbar spine BMC. Analyses accounted for baseline gynecological age (years pre- or postmenarche), baseline bone status, adult body size and interscan body size change. Gymnastics training was evaluated as a potentially independent predictor, but did not improve models for any outcomes (p > .07). Premenarcheal bone traits were strong predictors of most adult outcomes (semipartial r2 = .21-0.59, p ≤ .001). Adult 1/3 radius and subhead BMC were predicted by both total PA and PA 1-3 years postmenarche (p < .03). PA 3-5 years postmenarche predicted femoral narrow neck width, endosteal diameter, and buckling ratio (p < .05). Thus, participation in organized physical activity programs throughout middle and high school may reduce lifetime fracture risk in females. PMID:25386845

  10. Self-assembly of active colloidal molecules with dynamic function

    NASA Astrophysics Data System (ADS)

    Soto, Rodrigo; Golestanian, Ramin

    Catalytically active colloids maintain non-equilibrium conditions in which they produce and deplete chemicals at their surface. While individual colloids that are symmetrically coated do not exhibit dynamical activity, the concentration fields resulting from their chemical activity decay as 1/r and produce gradients that attract or repel other colloids depending on their surface chemistry and ambient variables. This results in a non-equilibrium analogue of ionic systems, but with the remarkable novel feature of action-reaction symmetry breaking. In dilute conditions these active colloids join up to form molecules via generalized ionic bonds. Colloids are found to join up to form self-assembled molecules that could be inert or have spontaneous activity in the form of net translational velocity and spin depending on their symmetry properties and their constituents. As the interactions do not satisfy detailed-balance, it is possible to achieve structures with time dependent functionality. We study a molecule that adopts spontaneous oscillations and another that exhibits a run-and-tumble dynamics similar to bacteria. Our study shows that catalytically active colloids could be used for designing self-assembled structures that posses dynamical functionalities.

  11. Differential expression of active zone proteins in neuromuscular junctions suggests functional diversification.

    PubMed

    Juranek, Judyta; Mukherjee, Konark; Rickmann, Michael; Martens, Henrik; Calka, Jaroslaw; Südhof, Thomas C; Jahn, Reinhard

    2006-12-01

    Nerve terminals of the central nervous system (CNS) contain specialized release sites for synaptic vesicles, referred to as active zones. They are characterized by electron-dense structures that are tightly associated with the presynaptic plasma membrane and organize vesicle docking and priming sites. Recently, major protein constituents of active zones have been identified, including the proteins Piccolo, Bassoon, RIM, Munc13, ERCs/ELKs/CASTs and liprins. While it is becoming apparent that each of these proteins is essential for synaptic function in the CNS, it is not known to what extent these proteins are involved in synaptic function of the peripheral nervous system. Somatic neuromuscular junctions contain morphologically and functionally defined active zones with similarities to CNS synapses. In contrast, sympathetic neuromuscular varicosities lack active zone-like morphological specializations. Using immunocytochemistry at the light and electron microscopic level we have now performed a systematic investigation of all five major classes of active zone proteins in peripheral neuromuscular junctions. Our results show that somatic neuromuscular endplates contain a full complement of all active zone proteins. In contrast, varicosities of the vas deferens contain a subset of active zone proteins including Bassoon and ELKS2, with the other four components being absent. We conclude that Bassoon and ELKS2 perform independent and specialized functions in synaptic transmission of autonomic synapses.

  12. Chemical Signaling and Functional Activation in Colloidosome-Based Protocells.

    PubMed

    Sun, Shiyong; Li, Mei; Dong, Faqin; Wang, Shengjie; Tian, Liangfei; Mann, Stephen

    2016-04-13

    An aqueous-based microcompartmentalized model involving the integration of partially hydrophobic Fe(III)-rich montmorillonite (FeM) clay particles as structural and catalytic building blocks for colloidosome membrane assembly, self-directed membrane remodeling, and signal-induced protocell communication is described. The clay colloidosomes exhibit size- and charge-selective permeability, and show dual catalytic functions involving spatially confined enzyme-mediated dephosphorylation and peroxidase-like membrane activity. The latter is used for the colloidosome-mediated synthesis and assembly of a temperature-responsive poly(N-isopropylacrylamide)(PNIPAM)/clay-integrated hybrid membrane. In situ PNIPAM elaboration of the membrane is coupled to a glucose oxidase (GOx)-mediated signaling pathway to establish a primitive model of chemical communication and functional activation within a synthetic "protocell community" comprising a mixed population of GOx-containing silica colloidosomes and alkaline phosphatase (ALP)-containing FeM-clay colloidosomes. Triggering the enzyme reaction in the silica colloidosomes gives a hydrogen peroxide signal that induces polymer wall formation in a coexistent population of the FeM-clay colloidosomes, which in turn generates self-regulated membrane-gated ALP-activity within the clay microcompartments. The emergence of new functionalities in inorganic colloidosomes via chemical communication between different protocell populations provides a first step toward the realization of interacting communities of synthetic functional microcompartments. PMID:26923794

  13. Function and biotechnology of extremophilic enzymes in low water activity

    PubMed Central

    2012-01-01

    Enzymes from extremophilic microorganisms usually catalyze chemical reactions in non-standard conditions. Such conditions promote aggregation, precipitation, and denaturation, reducing the activity of most non-extremophilic enzymes, frequently due to the absence of sufficient hydration. Some extremophilic enzymes maintain a tight hydration shell and remain active in solution even when liquid water is limiting, e.g. in the presence of high ionic concentrations, or at cold temperature when water is close to the freezing point. Extremophilic enzymes are able to compete for hydration via alterations especially to their surface through greater surface charges and increased molecular motion. These properties have enabled some extremophilic enzymes to function in the presence of non-aqueous organic solvents, with potential for design of useful catalysts. In this review, we summarize the current state of knowledge of extremophilic enzymes functioning in high salinity and cold temperatures, focusing on their strategy for function at low water activity. We discuss how the understanding of extremophilic enzyme function is leading to the design of a new generation of enzyme catalysts and their applications to biotechnology. PMID:22480329

  14. Function and biotechnology of extremophilic enzymes in low water activity.

    PubMed

    Karan, Ram; Capes, Melinda D; Dassarma, Shiladitya

    2012-02-02

    Enzymes from extremophilic microorganisms usually catalyze chemical reactions in non-standard conditions. Such conditions promote aggregation, precipitation, and denaturation, reducing the activity of most non-extremophilic enzymes, frequently due to the absence of sufficient hydration. Some extremophilic enzymes maintain a tight hydration shell and remain active in solution even when liquid water is limiting, e.g. in the presence of high ionic concentrations, or at cold temperature when water is close to the freezing point. Extremophilic enzymes are able to compete for hydration via alterations especially to their surface through greater surface charges and increased molecular motion. These properties have enabled some extremophilic enzymes to function in the presence of non-aqueous organic solvents, with potential for design of useful catalysts. In this review, we summarize the current state of knowledge of extremophilic enzymes functioning in high salinity and cold temperatures, focusing on their strategy for function at low water activity. We discuss how the understanding of extremophilic enzyme function is leading to the design of a new generation of enzyme catalysts and their applications to biotechnology.

  15. New Pyrrole Derivatives with Potent Tubulin Polymerization Inhibiting Activity As Anticancer Agents Including Hedgehog-Dependent Cancer

    PubMed Central

    La Regina, Giuseppe; Bai, Ruoli; Coluccia, Antonio; Famiglini, Valeria; Pelliccia, Sveva; Passacantilli, Sara; Mazzoccoli, Carmela; Ruggieri, Vitalba; Sisinni, Lorenza; Bolognesi, Alessio; Rensen, Whilelmina Maria; Miele, Andrea; Nalli, Marianna; Alfonsi, Romina; Di Marcotullio, Lucia; Gulino, Alberto; Brancale, Andrea; Novellino, Ettore; Dondio, Giulio; Vultaggio, Stefania; Varasi, Mario; Mercurio, Ciro; Hamel, Ernest; Lavia, Patrizia; Silvestri, Romano

    2014-01-01

    We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway. PMID:25025991

  16. XIAP reverses various functional activities of FRNK in endothelial cells

    SciTech Connect

    Ahn, Sunyoung; Kim, Hyun Jeong; Chi, Sung-Gil; Park, Heonyong

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. Black-Right-Pointing-Pointer XIAP binds the FRNK domain of FAK. Black-Right-Pointing-Pointer XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. Black-Right-Pointing-Pointer XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

  17. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis.

  18. EGFR regulates macrophage activation and function in bacterial infection.

    PubMed

    Hardbower, Dana M; Singh, Kshipra; Asim, Mohammad; Verriere, Thomas G; Olivares-Villagómez, Danyvid; Barry, Daniel P; Allaman, Margaret M; Washington, M Kay; Peek, Richard M; Piazuelo, M Blanca; Wilson, Keith T

    2016-09-01

    EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis. PMID:27482886

  19. Physical activity and obesity mediate the association between childhood motor function and adolescents' academic achievement.

    PubMed

    Kantomaa, Marko T; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-29

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

  20. Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

    PubMed Central

    Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-01

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents’ academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents’ academic achievement via physical inactivity (B = –0.023, 95% confidence interval = –0.031, –0.015) and obesity (B = –0.025, 95% confidence interval = –0.039, –0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents’ academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement. PMID:23277558

  1. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    PubMed

    Mahoney, J Matthew; Titiz, Ali S; Hernan, Amanda E; Scott, Rod C

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation.

  2. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    PubMed

    Mahoney, J Matthew; Titiz, Ali S; Hernan, Amanda E; Scott, Rod C

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID:26866597

  3. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay

    PubMed Central

    Mahoney, J. Matthew; Titiz, Ali S.; Hernan, Amanda E.; Scott, Rod C.

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID:26866597

  4. Active Acetylcholinesterase Immobilization on a Functionalized Silicon Surface.

    PubMed

    Khaldi, K; Sam, S; Gouget-Laemmel, A C; Henry de Villeneuve, C; Moraillon, A; Ozanam, F; Yang, J; Kermad, A; Ghellai, N; Gabouze, N

    2015-08-01

    In this work, we studied the attachment of active acetylcholinesterase (AChE) enzyme on a silicon substrate as a potential biomarker for the detection of organophosphorous (OP) pesticides. A multistep functionalization strategy was developed on a crystalline silicon surface: a carboxylic acid-terminated monolayer was grafted onto a hydrogen-terminated silicon surface by photochemical hydrosilylation, and then AChE was covalently attached through amide bonds using an activation EDC/NHS process. Each step of the modification was quantitatively characterized by ex-situ Fourier transform infrared spectroscopy in attenuated-total-reflection geometry (ATR-FTIR) and atomic force microscopy (AFM). The kinetics of enzyme immobilization was investigated using in situ real-time infrared spectroscopy. The enzymatic activity of immobilized acetylcholinesterase enzymes was determined with a colorimetric test. The surface concentration of active AChE was estimated to be Γ = 1.72 × 10(10) cm(-2).

  5. Pressure is not a state function for generic active fluids

    NASA Astrophysics Data System (ADS)

    Solon, A. P.; Fily, Y.; Baskaran, A.; Cates, M. E.; Kafri, Y.; Kardar, M.; Tailleur, J.

    2015-08-01

    Pressure is the mechanical force per unit area that a confined system exerts on its container. In thermal equilibrium, it depends only on bulk properties--such as density and temperature--through an equation of state. Here we show that in a wide class of active systems the pressure depends on the precise interactions between the active particles and the confining walls. In general, therefore, active fluids have no equation of state. Their mechanical pressure exhibits anomalous properties that defy the familiar thermodynamic reasoning that holds in equilibrium. The pressure remains a function of state, however, in some specific and well-studied active models that tacitly restrict the character of the particle-wall and/or particle-particle interactions.

  6. Product and rate determinations with chemically activated nucleotides in the presence of various prebiotic materials, including other mono- and polynucleotides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Alberas, D. J.; Rosenbach, M. T.; Bernasconi, C. F.; Chang, S.

    1991-01-01

    We are investigating the reactions of ImpN's in the presence of a number of prebiotically plausible materials, such as metal ions, phosphate, amines and other nucleotides and hope to learn more about the stability/reactivity of ImpN's in a prebiotic aqueous environment. We find that, in the presence of phosphate, ImpN's form substantial amounts of diphosphate nucleotides. These diphosphate nucleotides are not very good substrates for template directed reactions, but are chemically activated and are known to revert to the phosphoimidazolides in the presence of imidazole under solid state conditions. With respect to our studies of the oligomerization reaction, the determination of the dimerization rate constant of a specific ImpN (guanosine 5'-phospho 2 methylimidazolide) both in the absence and the presence of the template leads to the conclusion that at 37 C the dimerization is not template directed, although the subsequent polymerization steps are. In other words, this specific polynucleotide synthesizing system favors the elongation of oligonucleotides as compared with the formation of dimers and trimers. This favoring of the synthesis of long as opposed to short oligonucleotides may be regarded as a rudimentary example of natural selection at the molecular level.

  7. A comparison of methods of assessment of body composition including neutron activation analysis of total body nitrogen.

    PubMed

    Lukaski, H C; Mendez, J; Buskirk, E R; Cohn, S H

    1981-08-01

    Fourteen healthy men underwent determinations of total body nitrogen (TBN) by prompt gamma neutron activation analysis and total body potassium (TBK) by whole body counting to estimate the muscle and nonmuscle components of the fat-free body mass (FFBM) and their protein contents. Comparison of FFBM estimated from TBN and TBK (60.6 +/- 6.9 kg, mean +/- SD), densitometry (62.3 +/- 7.1 kg), TBK alone (62.2 +/- 8.0 kg) and TBW (63.9 +/- 7.8 kg) showed no differences among the techniques. Similarly, there were neither differences in fat mass nor percent body fat among the methods. Analysis of the chemical composition of FFBM of this group showed TBK/FFBM = 62.6 +/- 2.3 mEq/kg, TBW/FFBM = 74.6 +/- 0.2%, TBN/FFBM = 32.74 +/- 1.09 g/kg, protein/FFBM = 20.5+/- 0.7%. The calculated mineral content of the FFBM was 6.4%. These values are strikingly similar to the values calculated by direct chemical analysis. It was concluded that the combined TBN-TBK method is a valid technique for estimating body composition in man.

  8. Review: Production and functionality of active peptides from milk.

    PubMed

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  9. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally. PMID:16825516

  10. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  11. Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

    PubMed

    Busk, Peter Kamp; Lange, Lene

    2013-06-01

    Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision. PMID:23524681

  12. Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

    PubMed

    Busk, Peter Kamp; Lange, Lene

    2013-06-01

    Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision.

  13. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1990-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  14. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1988-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membanes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanime derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  15. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, H.K.; Wamser, C.C.

    1990-04-17

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  16. Including screening in van der Waals corrected density functional theory calculations: the case of atoms and small molecules physisorbed on graphene.

    PubMed

    Silvestrelli, Pier Luigi; Ambrosetti, Alberto

    2014-03-28

    The Density Functional Theory (DFT)/van der Waals-Quantum Harmonic Oscillator-Wannier function (vdW-QHO-WF) method, recently developed to include the vdW interactions in approximated DFT by combining the quantum harmonic oscillator model with the maximally localized Wannier function technique, is applied to the cases of atoms and small molecules (X=Ar, CO, H2, H2O) weakly interacting with benzene and with the ideal planar graphene surface. Comparison is also presented with the results obtained by other DFT vdW-corrected schemes, including PBE+D, vdW-DF, vdW-DF2, rVV10, and by the simpler Local Density Approximation (LDA) and semilocal generalized gradient approximation approaches. While for the X-benzene systems all the considered vdW-corrected schemes perform reasonably well, it turns out that an accurate description of the X-graphene interaction requires a proper treatment of many-body contributions and of short-range screening effects, as demonstrated by adopting an improved version of the DFT/vdW-QHO-WF method. We also comment on the widespread attitude of relying on LDA to get a rough description of weakly interacting systems. PMID:24697424

  17. Including screening in van der Waals corrected density functional theory calculations: the case of atoms and small molecules physisorbed on graphene.

    PubMed

    Silvestrelli, Pier Luigi; Ambrosetti, Alberto

    2014-03-28

    The Density Functional Theory (DFT)/van der Waals-Quantum Harmonic Oscillator-Wannier function (vdW-QHO-WF) method, recently developed to include the vdW interactions in approximated DFT by combining the quantum harmonic oscillator model with the maximally localized Wannier function technique, is applied to the cases of atoms and small molecules (X=Ar, CO, H2, H2O) weakly interacting with benzene and with the ideal planar graphene surface. Comparison is also presented with the results obtained by other DFT vdW-corrected schemes, including PBE+D, vdW-DF, vdW-DF2, rVV10, and by the simpler Local Density Approximation (LDA) and semilocal generalized gradient approximation approaches. While for the X-benzene systems all the considered vdW-corrected schemes perform reasonably well, it turns out that an accurate description of the X-graphene interaction requires a proper treatment of many-body contributions and of short-range screening effects, as demonstrated by adopting an improved version of the DFT/vdW-QHO-WF method. We also comment on the widespread attitude of relying on LDA to get a rough description of weakly interacting systems.

  18. Including screening in van der Waals corrected density functional theory calculations: The case of atoms and small molecules physisorbed on graphene

    SciTech Connect

    Silvestrelli, Pier Luigi; Ambrosetti, Alberto

    2014-03-28

    The Density Functional Theory (DFT)/van der Waals-Quantum Harmonic Oscillator-Wannier function (vdW-QHO-WF) method, recently developed to include the vdW interactions in approximated DFT by combining the quantum harmonic oscillator model with the maximally localized Wannier function technique, is applied to the cases of atoms and small molecules (X=Ar, CO, H{sub 2}, H{sub 2}O) weakly interacting with benzene and with the ideal planar graphene surface. Comparison is also presented with the results obtained by other DFT vdW-corrected schemes, including PBE+D, vdW-DF, vdW-DF2, rVV10, and by the simpler Local Density Approximation (LDA) and semilocal generalized gradient approximation approaches. While for the X-benzene systems all the considered vdW-corrected schemes perform reasonably well, it turns out that an accurate description of the X-graphene interaction requires a proper treatment of many-body contributions and of short-range screening effects, as demonstrated by adopting an improved version of the DFT/vdW-QHO-WF method. We also comment on the widespread attitude of relying on LDA to get a rough description of weakly interacting systems.

  19. Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells

    PubMed Central

    2015-01-01

    DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other AdoMet-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line. PMID:24387159

  20. Novel stilbenoids, including cannabispiradienone glycosides, from Tragopogon tommasinii (Asteraceae, Cichorieae) and their potential anti-inflammatory activity.

    PubMed

    Granica, Sebastian; Piwowarski, Jakub P; Randazzo, Antonio; Schneider, Peter; Żyżyńska-Granica, Barbara; Zidorn, Christian

    2015-09-01

    A phytochemical investigation of Tragopogon tommasinii Sch.Bip. (Asteraceae, Cichorieae) yielded a total of 21 natural products, two simple phenolic acids (4-hydroxybenzoic acid and p-coumaric acid), four caffeic acid derivatives (chlorogenic acid, 3-O-caffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, and 4,5-O-dicaffeoylquinic acid), six flavonoids (luteolin, luteolin 7-O-glucoside, vitexin, orientin, quercetin 3-O-glucoside, and isorhamnetin 3-O-glucoside), three simple bibenzyls [2-carboxyl-5-hydroxy-3-methoxy-4'-β-glucopyranosyl-oxybibenzyl, 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxy-5,4'-dihydroxy-3'-methoxybibenzyl, 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxy-4'-dihydroxy-5,3'-dimethoxybibenzyl], three phtalides [3-(4-β-glucopyranosyloxybenzyl)-7-hydroxy-5-methoxyphtalide, 7-β-glucopyranosyloxy-(S)-3-(4-hydroxybenzyl)-5-methoxyphtalide, and 7-(1→6)-α-rhamnosyl-β-glucopyranosyloxy-(S)-3-(4-hydroxybenzyl)-5-methoxyphtalide], two cannabispiradienone derivatives [3-O-β-glucopyranosyldemethoxycannabispiradienone and 3-caffeoyl-(9→5)-β-apiosyl-(1→6)-β-glucopyranosyloxydemethoxycannabispiradienone], and tetra-N-coumaroyl spermine. The three bibenzyls, the latter two benzylphthalides, and both cannabispiradienone derivatives represent new natural compounds and all compounds, except the caffeic acid derivatives and the flavonoids were new for T. tommasinii. The structures were established by HR mass spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy. Moreover, the potential anti-inflammatory activities of the new compounds were assayed using human neutrophils and their production of IL-1b, IL-8, TNF-α and MMP-9 as well as the expression of TLR-4, respectively.

  1. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... program, except that no amounts provided under the grant may be used to pay the cost of pension benefits... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What functions and activities constitute programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING...

  2. 20 CFR 641.864 - What functions and activities constitute programmatic activity costs?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... program, except that no amounts provided under the grant may be used to pay the cost of pension benefits... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false What functions and activities constitute programmatic activity costs? 641.864 Section 641.864 Employees' Benefits EMPLOYMENT AND TRAINING...

  3. FUNCTION FOLLOWS FORM: ACTIVATION OF SHAPE & FUNCTION FEATURES DURING OBJECT IDENTIFICATION

    PubMed Central

    Yee, Eiling; Huffstetler, Stacy; Thompson-Schill, Sharon L.

    2011-01-01

    Most theories of semantic memory characterize knowledge of a given object as comprising a set of semantic features. But how does conceptual activation of these features proceed during object identification? We present the results of a pair of experiments that demonstrate that object recognition is a dynamically unfolding process in which function follows form. We used eye movements to explore whether activating one object’s concept leads to the activation of others that share perceptual (shape) or abstract (function) features. Participants viewed four-picture displays and clicked on the picture corresponding to a heard word. In critical trials, the conceptual representation of one of the objects in the display was similar in shape or function (i.e., its purpose) to the heard word. Importantly, this similarity was not apparent in the visual depictions (e.g., for the target “frisbee,” the shape-related object was a triangular slice of pizza – a shape that a frisbee cannot take); preferential fixations on the related object were therefore attributable to overlap of the conceptual representations on the relevant features. We observed relatedness effects for both shape and function, but shape effects occurred earlier than function effects. We discuss the implications of these findings for current accounts of the representation of semantic memory. PMID:21417543

  4. Polyhexamethylene biguanide functionalized cationic silver nanoparticles for enhanced antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Ashraf, Sumaira; Akhtar, Nasrin; Ghauri, Muhammad Afzal; Rajoka, Muhammad Ibrahim; Khalid, Zafar M.; Hussain, Irshad

    2012-05-01

    Polyhexamethylene biguanide (PHMB), a broad spectrum disinfectant against many pathogens, was used as a stabilizing ligand for the synthesis of fairly uniform silver nanoparticles. The particles formed were characterized using UV-visible spectroscopy, FTIR, dynamic light scattering, electrophoretic mobility, and TEM to measure their morphology and surface chemistry. PHMB-functionalized silver nanoparticles were then evaluated for their antimicrobial activity against a gram-negative bacterial strain, Escherichia coli. These silver nanoparticles were found to have about 100 times higher bacteriostatic and bactericidal activities, compared to the previous reports, due to the combined antibacterial effect of silver nanoparticles and PHMB. In addition to other applications, PHMB-functionalized silver nanoparticles would be extremely useful in textile industry due to the strong interaction of PHMB with cellulose fabrics.

  5. Functions of AMP-activated protein kinase in adipose tissue

    PubMed Central

    Daval, Marie; Foufelle, Fabienne; Ferré, Pascal

    2006-01-01

    AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Its functions have been extensively studied in muscles and liver. AMPK stimulates pathways which increase energy production (glucose transport, fatty acid oxidation) and switches off pathways which consume energy (lipogenesis, protein synthesis, gluconeogenesis). This has led to the concept that AMPK has an interesting pharmaceutical potential in situations of insulin resistance and it is indeed the target of existing drugs and hormones which improve insulin sensitivity. Adipose tissue is a key player in energy metabolism through the release of substrates and hormones involved in metabolism and insulin sensitivity. Activation of AMPK in adipose tissue can be achieved through situations such as fasting and exercise. Leptin and adiponectin as well as hypoglycaemic drugs are activators of adipose tissue AMPK. This activation probably involves changes in the AMP/ATP ratio and the upstream kinase LKB1. When activated, AMPK limits fatty acid efflux from adipocytes and favours local fatty acid oxidation. Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin-resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes. PMID:16709632

  6. Comparative studies of brain activation with MEG and functional MRI

    SciTech Connect

    George, J.S.; Aine, C.J.; Sanders, J.A.; Lewine, J.D.; Caprihan, A.

    1993-12-31

    The past two years have witnessed the emergence of MRI as a functional imaging methodology. Initial demonstrations involved the injection of a paramagnetic contrast agent and required ultrafast echo planar imaging capability to adequately resolve the passage of the injected bolus. By measuring the local reduction in image intensity due to magnetic susceptibility, it was possible to calculate blood volume, which changes as a function of neural activation. Later developments have exploited endogenous contrast mechanisms to monitor changes in blood volume or in venous blood oxygen content. Recently, we and others have demonstrated that it is possible to make such measurements in a clinical imager, suggesting that the large installed base of such machines might be utilized for functional imaging. Although it is likely that functional MRI (fMRI) will subsume some of the clinical and basic neuroscience applications now touted for MEG, it is also clear that these techniques offer different largely complementary, capabilities. At the very least, it is useful to compare and cross-validate the activation maps produced by these techniques. Such studies will be valuable as a check on results of neuromagnetic distributed current reconstructions and will allow better characterization of the relationship between neurophysiological activation and associated hemodynamic changes. A more exciting prospect is the development of analyses that combine information from the two modalities to produce a better description of underlying neural activity than is possible with either technique in isolation. In this paper we describe some results from initial comparative studies and outline several techniques that can be used to treat MEG and fMRI data within a unified computational framework.

  7. Kinetics of Hydrogen Radical Reactions with Toluene Including Chemical Activation Theory Employing System-Specific Quantum RRK Theory Calibrated by Variational Transition State Theory.

    PubMed

    Bao, Junwei Lucas; Zheng, Jingjing; Truhlar, Donald G

    2016-03-01

    Pressure-dependent reactions are ubiquitous in combustion and atmospheric chemistry. We employ a new calibration procedure for quantum Rice-Ramsperger-Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism to calculate the pressure-falloff effect of a radical association with an aromatic ring. The new theoretical framework is applied to the reaction of H with toluene, which is a prototypical reaction in the combustion chemistry of aromatic hydrocarbons present in most fuels. Both the hydrogen abstraction reactions and the hydrogen addition reactions are calculated. Our system-specific (SS) QRRK approach is adjusted with SS parameters to agree with multistructural canonical variational transition state theory with multidimensional tunneling (MS-CVT/SCT) at the high-pressure limit. The new method avoids the need for the usual empirical estimations of the QRRK parameters, and it eliminates the need for variational transition state theory calculations as a function of energy, although in this first application we do validate the falloff curves by comparing SS-QRRK results without tunneling to multistructural microcanonical variational transition state theory (MS-μVT) rate constants without tunneling. At low temperatures, the two approaches agree well with each other, but at high temperatures, SS-QRRK tends to overestimate falloff slightly. We also show that the variational effect is important in computing the energy-resolved rate constants. Multiple-structure anharmonicity, torsional-potential anharmonicity, and high-frequency-mode vibrational anharmonicity are all included in the rate computations, and torsional anharmonicity effects on the density of states are investigated. Branching fractions, which are both temperature- and pressure-dependent (and for which only limited data is available from experiment), are predicted as a function of pressure. PMID:26841076

  8. Kinetics of Hydrogen Radical Reactions with Toluene Including Chemical Activation Theory Employing System-Specific Quantum RRK Theory Calibrated by Variational Transition State Theory.

    PubMed

    Bao, Junwei Lucas; Zheng, Jingjing; Truhlar, Donald G

    2016-03-01

    Pressure-dependent reactions are ubiquitous in combustion and atmospheric chemistry. We employ a new calibration procedure for quantum Rice-Ramsperger-Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism to calculate the pressure-falloff effect of a radical association with an aromatic ring. The new theoretical framework is applied to the reaction of H with toluene, which is a prototypical reaction in the combustion chemistry of aromatic hydrocarbons present in most fuels. Both the hydrogen abstraction reactions and the hydrogen addition reactions are calculated. Our system-specific (SS) QRRK approach is adjusted with SS parameters to agree with multistructural canonical variational transition state theory with multidimensional tunneling (MS-CVT/SCT) at the high-pressure limit. The new method avoids the need for the usual empirical estimations of the QRRK parameters, and it eliminates the need for variational transition state theory calculations as a function of energy, although in this first application we do validate the falloff curves by comparing SS-QRRK results without tunneling to multistructural microcanonical variational transition state theory (MS-μVT) rate constants without tunneling. At low temperatures, the two approaches agree well with each other, but at high temperatures, SS-QRRK tends to overestimate falloff slightly. We also show that the variational effect is important in computing the energy-resolved rate constants. Multiple-structure anharmonicity, torsional-potential anharmonicity, and high-frequency-mode vibrational anharmonicity are all included in the rate computations, and torsional anharmonicity effects on the density of states are investigated. Branching fractions, which are both temperature- and pressure-dependent (and for which only limited data is available from experiment), are predicted as a function of pressure.

  9. Studies of higher nervous activity in functional phychoses.

    PubMed

    Astrup, C

    1975-01-01

    Psychiatric illnesses can be conceived of as experiments of nature, providing a variety of pathopsychological mechanisms which may elucidate normal psychological processes. Clinically the reactive psychoses are predominantly psychogenic reaction types. They present disturbances of higher nervous activity, similar to those of the neuroses. The unconditional reflex activity is practically as in normal controls, and the most outstanding finding was the large effect of psychodynamic complex structures. This is a physiological parallel to the clinical manifestations with great concern over experienced mental trauma. In the manic-depressive psychoses the most characteristic feature is a marked disturbance of unconditional reflex activity. This factor may be an important physiological mechanism underlying the more biological than psychodynamic reaction type and partly explain the changes of mood and associated interferences with sleep, body weight, sexual activity, aggression and other instinctual and vegetative functions. Schizophrenic psychoses also present changes of unconditional reflex activity, predominantly in the direction of inhibition of response. In addition there are severe dissociations within and between the three levels of unconditional reflexes and the two signaling systems. It is suggested that schizophrenia represents a functional maladaptation, which can be explained from the principles of autokinesis and schizokinesis established by Gantt in animal experiments. Prognostic models based on experimentally established impairment of performances were shown to predict long-term risks of schizophrenic defects just as well as models based on constellations of clinical symptoms. I would predict that psychophysiology and experimental psychology will become increasingly more important for establishing diagnosis and prognosis in the functional psychoses. The data of this article point toward a basis for a prophylactic psychiatry. PMID:1236657

  10. PREFACE: 9th International Fröhlich's Symposium: Electrodynamic Activity of Living Cells (Including Microtubule Coherent Modes and Cancer Cell Physics)

    NASA Astrophysics Data System (ADS)

    Cifra, Michal; Pokorný, Jirí; Kucera, Ondrej

    2011-12-01

    This volume contains papers presented at the International Fröhlich's Symposium entitled 'Electrodynamic Activity of Living Cells' (1-3 July 2011, Prague, Czech Republic). The Symposium was the 9th meeting devoted to physical processes in living matter organized in Prague since 1987. The hypothesis of oscillation systems in living cells featured by non-linear interaction between elastic and electrical polarization fields, non-linear interactions between the system and the heat bath leading to energy downconversion along the frequency scale, energy condensation in the lowest frequency mode and creation of a coherent state was formulated by H Fröhlich, founder of the theory of dielectric materials. He assumed that biological activity is based not only on biochemical but also on biophysical mechanisms and that their disturbances form basic links along the cancer transformation pathway. Fröhlich outlined general ideas of non-linear physical processes in biological systems. The downconversion and the elastic-polarization interactions should be connected in a unified theory and the solution based on comprehensive non-linear characteristics. Biochemical and genetic research of biological systems are highly developed and have disclosed a variety of cellular and subcellular structures, chemical reactions, molecular information transfer, and genetic code sequences - including their pathological development. Nevertheless, the cancer problem is still a big challenge. Warburg's discovery of suppressed oxidative metabolism in mitochondria in cancer cells suggested the essential role of physical mechanisms (but his discovery has remained without impact on cancer research and on the study of physical properties of biological systems for a long time). Mitochondria, the power plants of the cell, have several areas of activity-oxidative energy production is connected with the formation of a strong static electric field around them, water ordering, and liberation of non

  11. Physical activity and cognitive function in individuals over 60 years of age: a systematic review

    PubMed Central

    Carvalho, Ashley; Rea, Irene Maeve; Parimon, Tanyalak; Cusack, Barry J

    2014-01-01

    Background It is unclear whether physical activity in later life is beneficial for maintenance of cognitive function. We performed a systematic review examining the effects of exercise on cognitive function in older individuals, and present possible mechanisms whereby physical activity may improve cognition. Methods Sources consisted of PubMed, Medline, CINAHL, the Cochrane Controlled Trials Register, and the University of Washington, School of Medicine Library Database, with a search conducted on August 15, 2012 for publications limited to the English language starting January 1, 2000. Randomized controlled trials including at least 30 participants and lasting at least 6 months, and all observational studies including a minimum of 100 participants for one year, were evaluated. All subjects included were at least 60 years of age. Results Twenty-seven studies met the inclusion criteria. Twenty-six studies reported a positive correlation between physical activity and maintenance or enhancement of cognitive function. Five studies reported a dose-response relationship between physical activity and cognition. One study showed a nonsignificant correlation. Conclusion The preponderance of evidence suggests that physical activity is beneficial for cognitive function in the elderly. However, the majority of the evidence is of medium quality with a moderate risk of bias. Larger randomized controlled trials are needed to clarify the association between exercise and cognitive function and to determine which types of exercise have the greatest benefit on specific cognitive domains. Despite these caveats, the current evidence suggests that physical activity may help to improve cognitive function and, consequently, delay the progression of cognitive impairment in the elderly. PMID:24748784

  12. Application of activity-based protein profiling to study enzyme function in adipocytes.

    PubMed

    Galmozzi, Andrea; Dominguez, Eduardo; Cravatt, Benjamin F; Saez, Enrique

    2014-01-01

    Activity-based protein profiling (ABPP) is a chemical proteomics approach that utilizes small-molecule probes to determine the functional state of enzymes directly in native systems. ABPP probes selectively label active enzymes, but not their inactive forms, facilitating the characterization of changes in enzyme activity that occur without alterations in protein levels. ABPP can be a tool superior to conventional gene expression and proteomic profiling methods to discover new enzymes active in adipocytes and to detect differences in the activity of characterized enzymes that may be associated with disorders of adipose tissue function. ABPP probes have been developed that react selectively with most members of specific enzyme classes. Here, using as an example the serine hydrolase family that includes many enzymes with critical roles in adipocyte physiology, we describe methods to apply ABPP analysis to the study of adipocyte enzymatic pathways.

  13. Jungle honey enhances immune function and antitumor activity.

    PubMed

    Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C; Sawai, Masaharu; Pinkerton, Kent E; Takeuchi, Minoru

    2011-01-01

    Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489

  14. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    PubMed Central

    Kasess, Christian H.; Meyer, Bernhard M.; Hofmaier, Tina; Diers, Kersten; Bartova, Lucie; Pail, Gerald; Huf, Wolfgang; Uzelac, Zeljko; Hartinger, Beate; Kalcher, Klaudius; Perkmann, Thomas; Haslacher, Helmuth; Meyer-Lindenberg, Andreas; Kasper, Siegfried; Freissmuth, Michael; Windischberger, Christian; Willeit, Matthäus; Lanzenberger, Rupert; Esterbauer, Harald; Brocke, Burkhard; Moser, Ewald; Sitte, Harald H.; Pezawas, Lukas

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax. Results The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity. Conclusion This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation. PMID:24667541

  15. The impact of chromospheric activity on observed initial mass functions

    SciTech Connect

    Stassun, Keivan G.; Scholz, Aleks; Dupuy, Trent J.; Kratter, Kaitlin M.

    2014-12-01

    Using recently established empirical calibrations for the impact of chromospheric activity on the radii, effective temperatures, and estimated masses of active low-mass stars and brown dwarfs, we reassess the shape of the initial mass function (IMF) across the stellar/substellar boundary in the Upper Sco star-forming region (age ∼ 5-10 Myr). We adjust the observed effective temperatures to warmer values using the observed strength of the chromospheric Hα emission, and redetermine the estimated masses of objects using pre-main-sequence evolutionary tracks in the H-R diagram. The effect of the activity-adjusted temperatures is to shift the objects to higher masses by 3%-100%. While the slope of the resulting IMF at substellar masses is not strongly changed, the peak of the IMF does shift from ≈0.06 to ≈0.11 M {sub ☉}. Moreover, for objects with masses ≲ 0.2 M {sub ☉}, the ratio of brown dwarfs to stars changes from ∼80% to ∼33%. These results suggest that activity corrections are essential for studies of the substellar mass function, if the masses are estimated from spectral types or from effective temperatures.

  16. Electrical activity patterns and the functional maturation of the neocortex.

    PubMed

    Kilb, Werner; Kirischuk, Sergei; Luhmann, Heiko J

    2011-11-01

    At the earliest developmental stages, sensory neocortical areas in various species reveal distinct patterns of spontaneous neuronal network activity. These activity patterns either propagate over large neocortical areas or synchronize local neuronal ensembles. In vitro and in vivo experiments indicate that these spontaneous activity patterns are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, cochlea, whiskers). At early stages spontaneous periphery-driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. These early local and large-scale neuronal activity patterns influence a variety of developmental processes during corticogenesis, such as neurogenesis, apoptosis, neuronal migration, differentiation and network formation. The experimental data also indicate that disturbances in early neuronal patterns may have an impact on the development of cortical layers, columns and networks. In this article we review our current knowledge on the origin of early electrical activity patterns in neocortical sensory areas and their functional implications on shaping developing cortical networks.

  17. Physical activity interventions and children's mental function: An introduction and overview

    PubMed Central

    Tomporowski, Phillip D.; Lambourne, Kate; Okumura, Michelle S.

    2011-01-01

    Background This review provides a historical overview of physical activity interventions designed by American educators and an evaluation of research that has assessed the effects of exercise on children's mental function. Method Historical descriptions of the emergence of American physical education doctrine throughout the 20th century were evaluated. Prior reviews of studies that assessed the effects of single acute bouts of exercise and the effects of chronic exercise training on children's mental function were examined and the results of recent studies were summarized. Results Physical activity interventions designed for American children have reflected two competing views: activities should promote physical fitness and activities should promote social, emotional, and intellectual development. Research results indicate that exercise fosters the emergence of children's mental function; particularly executive functioning. The route by which physical activity impacts mental functioning is complex and is likely moderated by several variables, including physical fitness level, health status, and numerous psycho-social factors. Conclusion Physical activity interventions for children should be designed to meet multiple objectives; e.g., optimize physical fitness, promote health-related behaviors that offset obesity, and facilitate mental development. PMID:21420981

  18. Transfer Function between EEG and BOLD Signals of Epileptic Activity

    PubMed Central

    Leite, Marco; Leal, Alberto; Figueiredo, Patrícia

    2013-01-01

    Simultaneous electroencephalogram (EEG)-functional Magnetic Resonance Imaging (fMRI) recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a hemodynamic response function to model the associated Blood Oxygen Level Dependent (BOLD) changes. Although more flexible approaches may allow a higher degree of complexity for the hemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent, and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity, and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept. PMID:23355832

  19. Insilico studies of organosulfur-functional active compounds in garlic.

    PubMed

    Singh, Yogendra P; Singh, Ram A

    2010-01-01

    Garlic has been used medicinally since antiquity because of its antimicrobial activity, anticancer activity, antioxidant activity, ability to reduce cardiovascular diseases, improving immune functions, and antidiabetic activities and also in reducing cardiovascular diseases and improving immune functions. Recent studies identify that the wide variety of medicinal functions are attributed to the sulfur compounds present in garlic. Epidemiological observations and laboratory studies in animal models have also showed anticarcinogenic potential of organosulfur compounds of garlic. In this study, in silico analysis of organosulfur compounds is reported using the methods of theoretical chemistry to elucidate the molecular properties of garlic as it is more time and cost efficient, reduces the number of wet experiments, and offers the possibility of replacing some animal tests with suitable in silico models. The analysis of molecular descriptors defined by Lipinski has been done. The solubility of drug in water has been determined as it is of useful importance in the process of drug discovery from molecular design to pharmaceutical formulation and biopharmacy. All toxicities associated with candidate drug have been calculated. P-Glycoprotein expressed in normal tissues as a cause of drug pharmacokinetics and pharmacodynamics has been examined. Drug-plasma protein binding and volume of distribution have also been calculated. To avoid rejection of drugs, it is becoming more important to determine pK(a), absorption, polar surface area, and other physiochemical properties associated with a drug, before synthetic work is undertaken. The present in silico study is aimed at examining these compounds of garlic to evaluate its possible efficacy and toxicity under conditions of actual use in humans. PMID:20641079

  20. Trigonometry, Including Snell's Theorem.

    ERIC Educational Resources Information Center

    Kent, David

    1980-01-01

    Aspects of the instruction of trigonometry in secondary school mathematics are reviewed. Portions of this document cover basic introductions, a student-developed theorem, the cosine rule, inverse functions, and a sample outdoor activity. (MP)

  1. Aspartame degradation as a function of "water activity".

    PubMed

    Bell, L N; Labuza, T P

    1991-01-01

    The incorporation of aspartame into an increasing number of foods necessitates evaluation of its degradation kinetics as a function of "water activity" (aw). The kinetics of degradation were followed in model systems as a function of initial pH, temperature, and aw. An increase in aw, for each 0.1 units in the 0.3 to 0.7 range, resulted in about a 30-80% increase in degradation rate, which then decreased only slowly up to dilute solution. The presence of oil increased the degradation rate at high aw, but glucose had no effect on the rate of aspartame loss. The activation energies for loss ranged from 25 to 20 kcal/mole, decreasing as aw increased, as expected. The rates as a function of pH showed that the actual pH of the water in the condensed phase, based on the Bronsted relationship, may be very different than the initial pH. This caused a shift in the pH at which the fastest rate of degradation occurred, as aw increased.

  2. [The gaze and functional hemispheric activation in normal subjects].

    PubMed

    Gallois, P; Hautecoeur, P; Ovelacq, E; Gras, P; Dereux, J F

    1985-01-01

    The aim of this work was to determine whether the study of lateral and vertical conjugated eye movement could serve as an indicator of the functional hemispheric activation. Questions of vocabulary, calculation, logic (V.C.L.) and visuo-spatial instructions, as well as music-listening (V.S.M.), were proposed to 60 control subjects (21 men, 39 women). They were divided in 4 groups of 15 according to their laterality (complete right handed, incomplete right handed, ambidextrous, left handed). Eye movements were recorded using a video system. Deviations of the eyes towards the right and left, upwards and downwards, as well as episodes of staring were noted. Concerning V.C.L. questions, there was a significant correlation between conjugated lateral eye movements and the contralateral hemisphere activation. The study of vertical eye movements revealed a correlation only in complete right-handed and left-handed subjects: deviation upwards during the left hemisphere activation, and downwards during the right hemisphere activation. This pattern of response was no longer found during V.S.M. questions which, in the 4 groups, evoked staring episodes in 56 to 72 per cent of the cases. The negative emotional stimuli (emotional words, non verbal stimuli, stressful situations) evoked preferentially, but independently of laterality, deviations towards the left and downwards in favor of the right hemisphere activation. This method of observation of eye movements seems therefore of significant interest in Neuropsychology, provided that methodologic rules are rigorously respected.

  3. Uncertainty in measurement: a review of monte carlo simulation using microsoft excel for the calculation of uncertainties through functional relationships, including uncertainties in empirically derived constants.

    PubMed

    Farrance, Ian; Frenkel, Robert

    2014-02-01

    The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more 'constants', each of which has an empirically derived numerical value. Such empirically derived 'constants' must also have associated uncertainties which propagate through the functional relationship

  4. 20 CFR 641.856 - What functions and activities constitute costs of administration?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., including: (i) Accounting, budgeting, financial, and cash management functions; (ii) Procurement and purchasing functions; (iii) Property management functions; (iv) Personnel management functions; (v) Payroll... management of the program; and (5) Costs of information systems related to administrative functions...

  5. Continuous monitoring of functional activities using wearable, wireless gyroscope and accelerometer technology.

    PubMed

    Wagenaar, Robert C; Sapir, Inbal; Zhang, Yuting; Markovic, Stacey; Vaina, Lucia M; Little, Thomas D C

    2011-01-01

    The development of functional activity monitors (FAMs) will allow rehabilitation researchers and clinicians to evaluate treatment efficacy, to monitor compliance to exercise instructions, and to provide real time feedback in the treatment of movement disorders during the performance of daily activities. The purpose of the present study was to develop and test a small sized wearable FAM system comprised of three sensors positioned on the sternum and both thighs, wireless Bluetooth transmission capability to a smartphone, and computationally efficient activity detection algorithms for the accurate detection of functional activities. Each sensor was composed of a tri-axial accelerometer and a tri-axial gyroscope. Computationally efficient activity recognition algorithms were developed, using a sliding window of 1 second, the variability of the tilt angle time series and power spectral analysis. In addition, it includes a decision tree that identifies postures such as sitting, standing and lying, walking at comfortable, slow and fast speeds, transitions between these functional activities (e.g, sit-to-stand and stand-to-sit), activity duration and step frequency. In a research lab setting the output of the FAM system, video recordings and a 3D motion analysis system were compared in 10 healthy young adults. The results show that the agreement between the FAM system and the video recordings ranged from 98.10% to 100% for all postures, transfers and walking periods. There were no significant differences in activity durations and step frequency between measurement instruments. PMID:22255423

  6. Relationship Between Cortical Thickness and Functional Activation in the Early Blind

    PubMed Central

    Anurova, Irina; Renier, Laurent A.; De Volder, Anne G.; Carlson, Synnöve; Rauschecker, Josef P.

    2015-01-01

    Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan. PMID:24518755

  7. Functional activity of mitochondria in cultured neural precursor cells.

    PubMed

    Plotnikov, E Yu; Marei, M V; Podgornyi, O V; Aleksandrova, M A; Zorov, D B; Sukhikh, G T

    2006-01-01

    We studied mitochondrial transmembrane potential of neural precursor cells forming neurospheres in culture. Uneven energization of mitochondria in neurosphere cells was detected. Heterogeneity of cells by the mitochondrial potential increased with neurosphere enlargement during culturing. Decrease in the mitochondrial potential in the central cells in large spheres, presumably caused by insufficient diffusion of oxygen and nutrients, can provoke their damage and death. Population of cells with high mitochondrial potential responded to addition of the nuclear dye by a decrease in mitochondrial potential, which can indicate functioning of ABCG2 complex in these cells, characteristic of undifferentiated stem cells. These data will help to create optimum conditions for culturing of neural stem cells for the maintenance of their maximum functional and proliferative activity. PMID:16929986

  8. Synthesis and psychotropic activity of functionally substituted diaziridines and bisdiaziridines

    SciTech Connect

    Kostyanovskii, R.G.; Shustov, G.V.; Nabiev, O.G.; Denisenko, S.N.; Sukhanova, S.A.; Lavretskaya, E.F.

    1987-04-01

    The authors examine the psychotropic activity of diaziridines which differ considerable in their structures and the C- and N-substituents. Diaziridines are monoamine oxidase inhibitors in the brain and, thus, are potential antidepressants. The acute toxicities and some pharmacological effects of diaziridines are shown. Mice were used in the experiments. The bisdiaziridines obtained differ in their /sup 1/H and /sup 13/C NMR spectra. The effect is presented of functionally substituted diaziridines on the effects of reserpine, 5-hydroxytryptophan, tryptamine, corazole, and apomorphine hypothermia.

  9. Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

    PubMed Central

    Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

    2014-01-01

    The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. PMID:24623976

  10. Active membrane having uniform physico-chemically functionalized ion channels

    DOEpatents

    Gerald, II, Rex E; Ruscic, Katarina J; Sears, Devin N; Smith, Luis J; Klingler, Robert J; Rathke, Jerome W

    2012-09-24

    The present invention relates to a physicochemically-active porous membrane for electrochemical cells that purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. One dimension of the pore surface has a macroscopic length (1 nm-1000 .mu.m) and is directed parallel to the direction of an electric field, which is produced between the cathode and the anode electrodes of an electrochemical cell. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

  11. Hemodynamic responses to functional activation accessed by optical imaging

    NASA Astrophysics Data System (ADS)

    Ni, Songlin; Li, Pengcheng; Yang, Yuanyuan; Lv, Xiaohua; Luo, Qingming

    2006-01-01

    A multi-wavelength light-emitting diode (LED) and laser diode (LD) based optical imaging system was developed to visualize the changes in cerebral blood flow, oxygenation following functional activation simultaneously in rodent cortex. The 2-D blood flow image was accessed by laser speckle contrast imaging, and the spectroscopic imaging of intrinsic signal was used for the calculation of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) concentration. The combination of spectroscopic imaging and laser speckle contrast imaging provides the capability to simultaneously investigate the spatial and temporal blood flow and hemoglobin concentration changes with high resolution, which may lead to a better understanding of the coupling between neuronal activation and vascular responses. The optical imaging system been built is compact and convenient to investigators. And it is reliable to acquire raw data. In present study, the hemodynamic responses to cortical spreading depression (CSD) in parietal cortex of ~-chloralose/urethan anesthetized rats were demonstrated.

  12. Physical Activity and Cognitive Function in Older Adults: The Mediating Effect of Depressive Symptoms.

    PubMed

    Vance, David E; Marson, Daniel C; Triebel, Kristen L; Ball, Karlene K; Wadley, Virginia G; Cody, Shameka L

    2016-01-01

    Depressive symptoms and social networks may influence the relationship between physical activity and cognition. Using structural equation modeling, depressive symptoms and social networks were examined as mediators between physical activity and cognition in community-dwelling older adults (N = 122), with a range of cognitive abilities (e.g., normal, mild cognitive impairment). The model included age, physical activity, sedentary behavior, sleeping, social networks, depressive symptoms, and cognitive function. A path was observed between physical activity, depressive symptoms, and cognition; specifically, those who were more physically active experienced less depression and better cognitive functioning. No relationship between social networks and cognition was found. This model fits the data well (goodness-of-fit index = .93, adjusted goodness-of-fit index = .90, root mean square error of approximation = .06). Results suggest that physical activity may mitigate depressive symptoms, with beneficial effects on cognitive functioning in both those with and without mild cognitive impairment. Suggestions for managing depression and improving cognitive functioning are provided. PMID:27224681

  13. Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

    PubMed Central

    Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

    2007-01-01

    Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

  14. Endothelial RIG-I activation impairs endothelial function

    SciTech Connect

    Asdonk, Tobias; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  15. Dual Function of Phosphoubiquitin in E3 Activation of Parkin.

    PubMed

    Walinda, Erik; Morimoto, Daichi; Sugase, Kenji; Shirakawa, Masahiro

    2016-08-01

    Mutations in the gene encoding parkin, an auto-inhibited E3 ubiquitin ligase that functions in the clearance of damaged mitochondria, are the most common cause of autosomal recessive juvenile Parkinsonism. The mechanism regulating parkin activation remains poorly understood. Here we show, by using isothermal titration calorimetry, solution NMR, and fluorescence spectroscopy, that parkin can bind ubiquitin and phosphomimetic ubiquitin by recognizing the canonical hydrophobic patch and C terminus of ubiquitin. The affinity of parkin for both phosphomimetic and unmodified ubiquitin is markedly enhanced upon removal of the ubiquitin-like (UBL) domain of parkin. This suggests that the agonistic binding of ubiquitin to parkin in trans is counterbalanced by the antagonistic activity of the parkin UBL domain in cis Intriguingly, UBL binding is enthalpy-driven, whereas ubiquitin binding is driven by an increase in the total entropy of the system. These thermodynamic differences are explained by different chemistry in the ubiquitin- and UBL-binding pockets of parkin and, as shown by molecular dynamics simulations, are not a consequence of changes in protein conformational entropy. Indeed, comparison of conformational fluctuations reveals that the RING1-IBR element becomes considerably more rigid upon complex formation. A model of parkin activation is proposed in which E2∼Ub binding triggers large scale diffusional motion of the RING2 domain toward the ubiquitin-stabilized RING1-IBR assembly to complete formation of the active parkin-E2∼Ub transfer complex. Thus, ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin. PMID:27284007

  16. Antihelminthic niclosamide modulates dendritic cells activation and function.

    PubMed

    Wu, Chieh-Shan; Li, Yi-Rong; Chen, Jeremy J W; Chen, Ying-Che; Chu, Chiang-Liang; Pan, I-Hong; Wu, Yu-Shan; Lin, Chi-Chen

    2014-01-01

    Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-γ production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-κB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases. PMID:24561310

  17. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    PubMed Central

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  18. Dextromethorphan inhibits activations and functions in dendritic cells.

    PubMed

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN- γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF- κ B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  19. Predicting activity approach based on new atoms similarity kernel function.

    PubMed

    Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

    2015-07-01

    Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods.

  20. Envelope periodic solutions for a discrete network with the Jacobi elliptic functions and the alternative (G'/G)-expansion method including the generalized Riccati equation

    NASA Astrophysics Data System (ADS)

    Tala-Tebue, E.; Tsobgni-Fozap, D. C.; Kenfack-Jiotsa, A.; Kofane, T. C.

    2014-06-01

    Using the Jacobi elliptic functions and the alternative ( G'/ G-expansion method including the generalized Riccati equation, we derive exact soliton solutions for a discrete nonlinear electrical transmission line in (2+1) dimension. More precisely, these methods are general as they lead us to diverse solutions that have not been previously obtained for the nonlinear electrical transmission lines. This study seeks to show that it is not often necessary to transform the equation of the network into a well-known differential equation before finding its solutions. The solutions obtained by the current methods are generalized periodic solutions of nonlinear equations. The shape of solutions can be well controlled by adjusting the parameters of the network. These exact solutions may have significant applications in telecommunication systems where solitons are used to codify or for the transmission of data.

  1. Running wheel activity restores MPTP-induced functional deficits.

    PubMed

    Fredriksson, Anders; Stigsdotter, Ingels Maria; Hurtig, Anders; Ewalds-Kvist, Béatrice; Archer, Trevor

    2011-03-01

    -Dopa tests. Running wheel activity attenuated markedly the loss of dopamine due to repeated administrations of MPTP. BDNF protein level in the parietal cortex was elevated by the MPTP insult and increased further by physical exercise. Physical running wheel exercise alleviated both the functional and biomarker expressions of MPTP-induced parkinsonism.

  2. Rasch analysis of the Persian version of PedsQLTM Oral Health Scale: further psychometric evaluation on item validity including differential item functioning

    PubMed Central

    Lin, Chung-Ying; Kumar, Santhosh; Pakpour, Amir H.

    2016-01-01

    Background: The study aimed to further evaluate the psychometric properties of one recently developed oral health related quality of life (OHRQoL) instrument (PedsQL Oral Health Scale), including student self-report and parent-proxy report. Specifically, we tested the item validity,threshold order, local dependency, and differential item functioning (DIF) across gender and rater. Methods: This is a cross-sectional study, and study population was recruited in Qazvin, Iran using one-stage sampling with the unit of school. Students and their parents (1529 dyads) separately completed the Persian version of PedsQL Oral Health Scale. The psychometric properties were analyzed using Rasch rating scale model, including item validity, threshold order for response categories, and DIF across gender (boys vs. girls in student self-report) and rater (student self report vs. parent-proxy report). Results: All items had satisfactory in fit and outfit mean square error. One disordering category (the response of often) was found in parent-proxy report, while all categories were ordered in student self-report. All items were DIF-trivial across gender and rater. Conclusion: PedsQL Oral Health Scale is a valid instrument to measure OHRQoL. However, our results indicated that the parent-proxy report was inferior to the student self-report, and healthcare providers should primarily use the student self-report. PMID:27579258

  3. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    PubMed

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined.

  4. Active chemisorption sites in functionalized ionic liquids for carbon capture.

    PubMed

    Cui, Guokai; Wang, Jianji; Zhang, Suojiang

    2016-07-25

    Development of novel technologies for the efficient and reversible capture of CO2 is highly desired. In the last decade, CO2 capture using ionic liquids has attracted intensive attention from both academia and industry, and has been recognized as a very promising technology. Recently, a new approach has been developed for highly efficient capture of CO2 by site-containing ionic liquids through chemical interaction. This perspective review focuses on the recent advances in the chemical absorption of CO2 using site-containing ionic liquids, such as amino-based ionic liquids, azolate ionic liquids, phenolate ionic liquids, dual-functionalized ionic liquids, pyridine-containing ionic liquids and so on. Other site-containing liquid absorbents such as amine-based solutions, switchable solvents, and functionalized ionic liquid-amine blends are also investigated. Strategies have been discussed for how to activate the existent reactive sites and develop novel reactive sites by physical and chemical methods to enhance CO2 absorption capacity and reduce absorption enthalpy. The carbon capture mechanisms of these site-containing liquid absorbents are also presented. Particular attention has been paid to the latest progress in CO2 capture in multiple-site interactions by amino-free anion-functionalized ionic liquids. In the last section, future directions and prospects for carbon capture by site-containing ionic liquids are outlined. PMID:27243042

  5. Structure activity relationships: their function in biological prediction

    SciTech Connect

    Schultz, T.W.

    1982-01-01

    Quantitative structure activity relationships provide a means of ranking or predicting biological effects based on chemical structure. For each compound used to formulate a structure activity model two kinds of quantitative information are required: (1) biological activity and (2) molecular properties. Molecular properties are of three types: (1) molecular shape, (2) physiochemical parameters, and (3) abstract quantitations of molecular structure. Currently the two best descriptors are the hydrophobic parameter, log 1-octanol/water partition coefficient (log P), and the /sup 1/X/sup v/(one-chi-v) molecular connectivity index. Biological responses can be divided into three main categories: (1) non-specific effects due to membrane perturbation, (2) non-specific effects due to interaction with functional groups of proteins, and (3) specific effects due to interaction with receptors. Twenty-six synthetic fossil fuel-related nitrogen-containing aromatic compounds were examined to determine the quantitative correlation between log P and /sup 1/X/sup v/ and population growth impairment of Tetrahymena pyriformis. Nitro-containing compounds are the most active, followed by amino-containing compounds and azaarenes. Within each analog series activity increases with alkyl substitution and ring addition. The planar model log BR = 0.5564 log P + 0.3000 /sup 1/X/sup v/ -2.0138 was determined using mono-nitrogen substituted compounds. Attempts to extrapolate this model to dinitrogen-containing molecules were, for the most part, unsuccessful because of a change in mode of action from membrane perturbation to uncoupling of oxidative phosphoralation.

  6. An investigation into the relationship between age and physiological function in highly active older adults

    PubMed Central

    Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

    2015-01-01

    Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding

  7. Estimation of spatiotemporal neural activity using radial basis function networks.

    PubMed

    Anderson, R W; Das, S; Keller, E L

    1998-12-01

    We report a method using radial basis function (RBF) networks to estimate the time evolution of population activity in topologically organized neural structures from single-neuron recordings. This is an important problem in neuroscience research, as such estimates may provide insights into systems-level function of these structures. Since single-unit neural data tends to be unevenly sampled and highly variable under similar behavioral conditions, obtaining such estimates is a difficult task. In particular, a class of cells in the superior colliculus called buildup neurons can have very narrow regions of saccade vectors for which they discharge at high rates but very large surround regions over which they discharge at low, but not zero, levels. Estimating the dynamic movement fields for these cells for two spatial dimensions at closely spaced timed intervals is a difficult problem, and no general method has been described that can be applied to all buildup cells. Estimation of individual collicular cells' spatiotemporal movement fields is a prerequisite for obtaining reliable two-dimensional estimates of the population activity on the collicular motor map during saccades. Therefore, we have developed several computational-geometry-based algorithms that regularize the data before computing a surface estimation using RBF networks. The method is then expanded to the problem of estimating simultaneous spatiotemporal activity occurring across the superior colliculus during a single movement (the inverse problem). In principle, this methodology could be applied to any neural structure with a regular, two-dimensional organization, provided a sufficient spatial distribution of sampled neurons is available.

  8. A poultry-intestinal isolate of Campylobacter jejuni produces a bacteriocin (CUV-3) active against a range of Gram positive bacterial pathogens including Clostridium perfringens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly isolated bacteriocin, CUV-3, produced by a poultry cecal isolate of Campylobacter jejuni strain CUV-3 had inhibitory activity against several Gram positive bacteria including Clostridium perfringens (38 strains), Staphylococcus aureus, Staph.epidermidis and Listeria monocytogenes. The pept...

  9. Including Youth with Intellectual Disabilities in Health Promotion Research: Development and Reliability of a Structured Interview to Assess the Correlates of Physical Activity among Youth

    ERIC Educational Resources Information Center

    Curtin, Carol; Bandini, Linda G.; Must, Aviva; Phillips, Sarah; Maslin, Melissa C. T.; Lo, Charmaine; Gleason, James M.; Fleming, Richard K.; Stanish, Heidi I.

    2016-01-01

    Background: The input of youth with intellectual disabilities in health promotion and health disparities research is essential for understanding their needs and preferences. Regular physical activity (PA) is vital for health and well-being, but levels are low in youth generally, including those with intellectual disabilities. Understanding the…

  10. Preparation of functionalized and metal-impregnated activated carbon by a single-step activation method

    NASA Astrophysics Data System (ADS)

    Dastgheib, Seyed A.; Ren, Jianli; Rostam-Abadi, Massoud; Chang, Ramsay

    2014-01-01

    A rapid method to prepare functionalized and metal-impregnated activated carbon from coal is described in this paper. A mixture of ferric chloride and a sub-bituminous coal was used to demonstrate simultaneous coal activation, chlorine functionalization, and iron/iron oxides impregnation in the resulting porous carbon products. The FeCl3 concentration in the mixture, the method to prepare the FeCl3-coal mixture (solid mixing or liquid impregnation), and activation atmosphere and temperature impacted the surface area and porosity development, Cl functionalization, and iron species impregnation and dispersion in the carbon products. Samples activated in nitrogen or a simulated flue gas at 600 or 1000 °C for 1-2 min had surface areas up to ∼800 m2/g, bulk iron contents up to 18 wt%, and surface chlorine contents up to 27 wt%. Potential catalytic and adsorption application of the carbon materials was explored in catalytic wet air oxidation (CWAO) of phenol and adsorption of ionic mercury from aqueous solutions. Results indicated that impregnated activated carbons outperformed their non-impregnated counterparts in both the CWAO and adsorption tests.

  11. Functional role of lipid rafts in CD20 activity?

    PubMed

    Janas, Eva; Priest, Richard; Malhotra, Rajneesh

    2005-01-01

    CD20 is a B-lymphocyte-specific integral membrane protein, implicated in the regulation of transmembrane calcium conductance, cell-cycle progression and B-lymphocyte proliferation. CD20 is proposed to function as a SOCC (store-operated calcium channel). SOCCs are activated by receptor-stimulated calcium depletion of intracellular stores. Sustained calcium conductivity across the plasma membrane mediated by SOCC activity is required for long-term calcium-dependent processes, such as transcriptional control and gene expression. Cross-linking of CD20 by antibodies (e.g. Rituxan) has been reported to induce a rapid redistribution of CD20 into specialized microdomains at the plasma membrane, known as lipid rafts. Recruitment of CD20 into lipid rafts and its homo-oligomerization are suggested to be crucial for CD20 activity and regulation. This review outlines recent biochemical studies characterizing the role of CD20 in calcium signalling in B-lymphocytes and evaluates an engagement of lipid rafts in the regulation of CD20-mediated calcium conductivity.

  12. Sexual function in Moroccan women with rheumatoid arthritis and its relationship with disease activity.

    PubMed

    Hari, Asmae; Rostom, Samira; Lahlou, Racha; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The objective of this study was to evaluate sexual function in women with rheumatoid arthritis (RA) using an auto-questionnaire Female Sexual Function Index (FSFI) and study its correlation with disease activity. Sixty patients with RA and 40 healthy controls were included in this exploratory study. Sociodemographic, clinical, and laboratory characteristics were assessed. The disease activity was assessed by auto-questionnaires Routine Assessment of Patient Index Data 3 (RAPID3) and Rheumatoid Arthritis Disease Activity Index 5 (RADAI5) judged by 28 DAS ESR. Sexual function was assessed by an auto-questionnaire specific for female sexuality: FSFI during the last 4 weeks. The definition of sexual dysfunction was considered by FSFI score less than or equal to 26.5. The mean age of RA patients and controls was 45.95 ± 9.3 and 45.01 ± 9.2, respectively. According to FSFI, the percentage of FSD in women with RA was significantly higher than that in the control group. All dimensions of sexuality were affected (desire, arousal, lubrication, orgasm, and satisfaction) except pain. The multivariate linear regression analysis indicated that the swollen joints and the RADAI5 were the independent variables of disease activity associated with sexual dysfunction in women with RA. This study suggests that sexual dysfunction among women suffering from rheumatoid arthritis is found when a targeted questionnaire is used to identify it and that the increased disease activity has a negative effect of sexual function. PMID:25677567

  13. Patterns of functional enzyme activity in fungus farming ambrosia beetles

    PubMed Central

    2012-01-01

    Introduction In wood-dwelling fungus-farming weevils, the so-called ambrosia beetles (Curculionidae: Scolytinae and Platypodinae), wood in the excavated tunnels is used as a medium for cultivating fungi by the combined action of digging larvae (which create more space for the fungi to grow) and of adults sowing and pruning the fungus. The beetles are obligately dependent on the fungus that provides essential vitamins, amino acids and sterols. However, to what extent microbial enzymes support fungus farming in ambrosia beetles is unknown. Here we measure (i) 13 plant cell-wall degrading enzymes in the fungus garden microbial consortium of the ambrosia beetle Xyleborinus saxesenii, including its primary fungal symbionts, in three compartments of laboratory maintained nests, at different time points after gallery foundation and (ii) four specific enzymes that may be either insect or microbially derived in X. saxesenii adult and larval individuals. Results We discovered that the activity of cellulases in ambrosia fungus gardens is relatively small compared to the activities of other cellulolytic enzymes. Enzyme activity in all compartments of the garden was mainly directed towards hemicellulose carbohydrates such as xylan, glucomannan and callose. Hemicellulolytic enzyme activity within the brood chamber increased with gallery age, whereas irrespective of the age of the gallery, the highest overall enzyme activity were detected in the gallery dump material expelled by the beetles. Interestingly endo-β-1,3(4)-glucanase activity capable of callose degradation was identified in whole-body extracts of both larvae and adult X. saxesenii, whereas endo-β-1,4-xylanase activity was exclusively detected in larvae. Conclusion Similar to closely related fungi associated with bark beetles in phloem, the microbial symbionts of ambrosia beetles hardly degrade cellulose. Instead, their enzyme activity is directed mainly towards comparatively more easily accessible hemicellulose

  14. Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

    PubMed

    Clarke, D O; Hilbish, K G; Waters, D G; Newcomb, D L; Chellman, G J

    2015-12-01

    The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected.

  15. Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin

    SciTech Connect

    LaMonte, C.S.; Yeh, S.D.; Straus, D.J.

    1986-04-01

    Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications.

  16. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control. PMID:16436103

  17. What are antibiotics? Archaic functions for modern activities.

    PubMed

    Davies, J

    1990-08-01

    Secondary metabolites are proposed to have played important roles in the evolution of the reactions of living forms on earth, in effecting and modulating reactions during biochemical evolution by chemical and structural interaction with 'receptor' sites in primitive macromolecular templates. For example, in the evolution of the translation system, as the polymerizing reactions became more complex and proteins became involved, the low molecular-weight effectors were functionally replaced by polypeptides, but retained their ability to interact with receptor sites in nucleic acids and proteins. Many of these low molecular-weight effectors now play a different role, that of antagonists, by interacting with the original receptor sites in macromolecular structures; this explains their contemporary activity as antibiotics.

  18. Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation.

    PubMed

    Amelio, Antonio L; Caputi, Massimo; Conkright, Michael D

    2009-09-16

    The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.

  19. Measurement of factor VIII activity using one-stage clotting assay: a calibration curve has not to be systematically included in each run.

    PubMed

    Lattes, S; Appert-Flory, A; Fischer, F; Jambou, D; Toulon, P

    2011-01-01

    Coagulation factor VIII (FVIII) is usually evaluated using activated partial thromboplastin time-based one-stage clotting assays. Guidelines for clotting factor assays indicate that a calibration curve should be included each time the assay is performed. Therefore, FVIII measurement is expensive, reagent- and time-consuming. The aim of this study was to compare FVIII activities obtained using the same fully automated assay that was calibrated once (stored calibration curve) or each time the assay was performed. Unique lots of reagents were used throughout the study. We analysed 255 frozen plasma samples from patients who were prescribed FVIII measurement including treated and untreated haemophilia A patients. Twenty-six runs were performed on a 28-week period, each including four lyophilized control and at most 10 patient plasma samples. In control samples, FVIII activities were not significantly different when the assay was performed using the stored calibration curve or was daily calibrated. The same applied to FVIII activities in patient plasma samples that were not significantly different throughout the measuring range of activities [68.3% (<1-179) vs. 67.6% (<1-177), P=0.48] and no relevant bias could be demonstrated when data were compared according to Bland and Altman. These results suggest that in the studied technical conditions, performing the FVIII assay using a stored calibration curve is reliable, for at least 6 months. Therefore, as far as the same lots of reagents are used, it is not mandatory to include a calibration curve each time the FVIII assay was performed. However, this strategy has to be validated if the assay is performed in different technical conditions.

  20. Functional, biophysical, and structural bases for antibacterial activity of tigecycline.

    PubMed

    Olson, Matthew W; Ruzin, Alexey; Feyfant, Eric; Rush, Thomas S; O'Connell, John; Bradford, Patricia A

    2006-06-01

    Tigecycline is a novel glycylcycline antibiotic that possesses broad-spectrum activity against many clinically relevant species of bacterial pathogens. The mechanism of action of tigecycline was delineated using functional, biophysical, and molecular modeling experiments in this study. Functional assays showed that tigecycline specifically inhibits bacterial protein synthesis with potency 3- and 20-fold greater than that of minocycline and tetracycline, respectively. Biophysical analyses demonstrated that isolated ribosomes bind tigecycline, minocycline, and tetracycline with dissociation constant values of 10(-8), 10(-7), and >10(-6) M, respectively. A molecular model of tigecycline bound to the ribosome was generated with the aid of a 3.40-angstrom resolution X-ray diffraction structure of the 30S ribosomal subunit from Thermus thermophilus. This model places tigecycline in the A site of the 30S subunit and involves substantial interactions with residues of H34 of the ribosomal subunit. These interactions were not observed in a model of tetracycline binding. Modeling data were consistent with the biochemical and biophysical data generated in this and other recent studies and suggested that tigecycline binds to bacterial ribosomes in a novel way that allows it to overcome tetracycline resistance due to ribosomal protection.

  1. Active plasma resonance spectroscopy: a functional analytic description

    NASA Astrophysics Data System (ADS)

    Lapke, M.; Oberrath, J.; Mussenbrock, T.; Brinkmann, R. P.

    2013-04-01

    The term ‘active plasma resonance spectroscopy’ denotes a class of diagnostic methods which employ the ability of plasmas to resonate on or near the plasma frequency. The basic idea dates back to the early days of discharge physics: a signal in the GHz range is coupled to the plasma via an electrical probe; the spectral response is recorded, and then evaluated with a mathematical model to obtain information on the electron density and other plasma parameters. In recent years, the concept has found renewed interest as a basis of industry compatible plasma diagnostics. This paper analyzes the diagnostic technique in terms of a general description based on functional analytic (or Hilbert Space) methods which hold for arbitrary probe geometries. It is shown that the response function of the plasma-probe system can be expressed as a matrix element of the resolvent of an appropriately defined dynamical operator. A specialization of the formalism to a symmetric probe design is given, as well as an interpretation in terms of a lumped circuit model consisting of series resonance circuits. We present ideas for an optimized probe design based on geometric and electrical symmetry.

  2. Common polymorphisms of ATP binding cassette transporter A1, including a functional promoter polymorphism, associated with plasma high density lipoprotein cholesterol levels in Turks.

    PubMed

    Hodoğlugil, Uğur; Williamson, David W; Huang, Yadong; Mahley, Robert W

    2005-12-01

    The role of high levels of high density lipoprotein cholesterol (HDL-C) in protection against development of atherosclerosis is generally attributed to its role in reverse cholesterol transport, and the ATP binding cassette transporter A1 (ABCA1) is a key element of this process. We examined polymorphisms in ABCA1 in Turks, a population characterized by very low HDL-C levels. We discovered 36 variations in ABCA1 and genotyped informative polymorphisms in over 2,300 subjects. The rare alleles of C-14T and V771M polymorphisms were associated with higher HDL-C levels in men and, in combination with the rare alleles of R219K and I883M, respectively, with higher HDL-C in both sexes. Rare alleles of the C-14T and V771M polymorphisms were more frequent in the high HDL-C (>OR=40mg/dl) than in the low HDL-C group (activity than the C allele (20-88%), depending on the cell line (P<0.05), suggesting its functionality. Haplotype construction and haplotype association with phenotype were performed in the promoter and coding region of ABCA1 separately. Analysis of the promoter haplotype block supported the association with the C-14T polymorphism. The C-14T and R219K polymorphisms were on different haplotype blocks. Analysis of the coding region structure revealed that the rare M allele of V771M was distributed predominantly among three common haplotypes, but the sum of their frequencies comprise only two-thirds of the frequency of the M allele. The rare alleles of the V771M and the I883M polymorphisms do not exist together on any of the common haplotypes. In conclusion, we describe a functional promoter polymorphism (C-14T) and a coding sequence variant (V771M) of ABCA1 and their interactions with two other variants (R219K and I883M) on plasma HDL-C levels in Turks.

  3. Interferon-γ activation of polymorphonuclear neutrophil function

    PubMed Central

    Ellis, Terri N; Beaman, Blaine L

    2004-01-01

    As current research illuminates the dynamic interplay between the innate and acquired immune responses, the interaction and communication between these two arms has yet to be fully investigated. Polymorphonuclear neutrophils (PMNs) and interferon-γ (IFN-γ) are known critical components of innate and acquired immunity, respectively. However, recent studies have demonstrated that these two components are not entirely isolated. Treatment of PMNs with IFN-γ elicits a variety of responses depending on stimuli and environmental conditions. These responses include increased oxidative burst, differential gene expression, and induction of antigen presentation. Many of these functions have been overlooked in PMNs, which have long been classified as terminal phagocytic cells incapable of protein synthesis. As this review reports, the old definition of the PMN is in need of an update, as these cells have demonstrated their ability to mediate the transition between the innate and acquired immune responses. PMID:15096178

  4. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  5. Atrial conduction times and left atrium mechanical functions in patients with active acromegaly.

    PubMed

    Ilter, A; Kırış, A; Kaplan, Ş; Kutlu, M; Şahin, M; Erem, C; Civan, N; Kangül, F

    2015-03-01

    The aim of this study was to evaluate atrial electromechanical delay (EMD), P wave dispersion (Pwd), and left atrial (LA) mechanical functions in patients with active acromegaly. Twenty-three patients with active acromegaly and 27 age- and sex-matched controls were included in this study. All atrial electromechanical interval parameters (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) were measured from mitral lateral annulus, mitral septal annulus, and right ventricular tricuspid annulus by tissue Doppler imaging. LA volumes were measured by the disk method in the apical four-chamber view and were indexed to the body surface area. Mechanical function parameters of LA were calculated. Pwd was performed by 12-lead electrocardiograms. Atrial electromechanical intervals (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) and Pwd were similar between patients with acromegaly and control subjects (all p > 0.05). LA volumes (maximum, minimum, and presystolic) and LA mechanical functions were not significantly different between the groups (all p > 0.05). Additionally, serum levels of growth hormone and insulin-like growth factor-1 were not correlated with atrial electromechanical parameters and LA mechanical functions. Atrial electrical conduction times were not prolonged and LA mechanical functions were not impaired in patients with active acromegaly compared with controls. And the prevalence of supraventricular arrhythmia risk may not increase in this population.

  6. Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

    PubMed Central

    Bradford, Aaron B; McNutt, Patrick M

    2015-01-01

    Functional synaptogenesis and network emergence are signature endpoints of neurogenesis. These behaviors provide higher-order confirmation that biochemical and cellular processes necessary for neurotransmitter release, post-synaptic detection and network propagation of neuronal activity have been properly expressed and coordinated among cells. The development of synaptic neurotransmission can therefore be considered a defining property of neurons. Although dissociated primary neuron cultures readily form functioning synapses and network behaviors in vitro, continuously cultured neurogenic cell lines have historically failed to meet these criteria. Therefore, in vitro-derived neuron models that develop synaptic transmission are critically needed for a wide array of studies, including molecular neuroscience, developmental neurogenesis, disease research and neurotoxicology. Over the last decade, neurons derived from various stem cell lines have shown varying ability to develop into functionally mature neurons. In this review, we will discuss the neurogenic potential of various stem cells populations, addressing strengths and weaknesses of each, with particular attention to the emergence of functional behaviors. We will propose methods to functionally characterize new stem cell-derived neuron (SCN) platforms to improve their reliability as physiological relevant models. Finally, we will review how synaptically active SCNs can be applied to accelerate research in a variety of areas. Ultimately, emphasizing the critical importance of synaptic activity and network responses as a marker of neuronal maturation is anticipated to result in in vitro findings that better translate to efficacious clinical treatments. PMID:26240679

  7. Functional response and population dynamics for fighting predator, based on activity distribution.

    PubMed

    Garay, József; Varga, Zoltán; Gámez, Manuel; Cabello, Tomás

    2015-03-01

    The classical Holling type II functional response, describing the per capita predation as a function of prey density, was modified by Beddington and de Angelis to include interference of predators that increases with predator density and decreases the number of killed prey. In the present paper we further generalize the Beddington-de Angelis functional response, considering that all predator activities (searching and handling prey, fight and recovery) have time duration, the probabilities of predator activities depend on the encounter probabilities, and hence on the prey and predator abundance, too. Under these conditions, the aim of the study is to introduce a functional response for fighting the predator and to analyse the corresponding dynamics, when predator-predator-prey encounters also occur. From this general approach, the Holling type functional responses can also be obtained as particular cases. In terms of the activity distribution, we give biologically interpretable sufficient conditions for stable coexistence. We consider two-individual (predator-prey) and three-individual (predator-predator-prey) encounters. In the three-individual encounter model there is a relatively higher fighting rate and a lower killing rate. Using numerical simulation, we surprisingly found that when the intrinsic prey growth rate and the conversion rate are small enough, the equilibrium predator abundance is higher in the three-individual encounter case. The above means that, when the equilibrium abundance of the predator is small, coexistence appears first in the three-individual encounter model.

  8. Preoperative evaluation of activity and function in patients with paralytic scoliosis.

    PubMed

    Larsson, E L; Aaro, S; Ahlinder, P; Oberg, B

    1998-01-01

    Preoperative evaluation of patients with paralytic scoliosis should take into account the consequences of surgery on the every day life of the patient. However, the parameters that are customarily used in these operations relate only to very narrow measures such as the angle of scoliosis or kyphosis. The aim of this study was to introduce a set of instruments appropriate for measuring both function and activities in paralytic scoliosis patients. The study took as its starting point the WHO International Classification of Impairments, Disabilities and Handicaps (ICIDH), in which an activity is described at the level of the individual and function at the level of the organ. A consecutive series of 100 paralytic scoliosis patients with 18 different diagnoses were evaluated preoperatively with a set of instruments that had been specially developed at Linköping hospital, in which the variables are classified according to the system used in the ICIDH. The set of instruments included general information and evaluation of activities and function--sitting, balance, weight distribution to sitting surface, angle of scoliosis, reaching, pain estimation, activities of daily living (ADL) Barthel and ADL Klein and Bell, care given, time spent resting, and seating supports). The results showed that patients with paralytic scoliosis constitute a heterogeneous group in activities and function. Even when the patients were grouped into four subgroups according to the Scoliosis Research Society Classification, they remained very heterogeneous. However, reaching, Klein and Bell Activities of Daily Living and pain could only evaluate patients who could understand verbal instructions. In those who could not, assessment relied more heavily on measures of function and level of dependence. It was concluded that the choice of assessment must be guided by the patient's ability to understand verbal instructions irrespective of his/her disorder. It is important to use the three levels

  9. Accuracy of Effective Core Potentials and Basis Sets for Density Functional Calculations, Including Relativistic Effects, As Illustrated by Calculations on Arsenic Compounds.

    PubMed

    Xu, Xuefei; Truhlar, Donald G

    2011-09-13

    For molecules containing the fourth-period element arsenic, we test (i, ii) the accuracy of all-electron (AE) basis sets from the def2-xZVP and ma-xZVP series (where xZ is S, TZ, or QZ), (iii) the accuracy of the 6-311G series of AE basis sets with additional polarization and diffuse functions, and (iv) the performance of effective core potentials (ECPs). The first set of tests involves basis-set convergence studies with eleven density functionals for five cases: equilibrium dissociation energy (De) of As2, vertical ionization potential (VIP) of As2, IP of As, acid dissociation of H3AsO4, and De of FeAs. A second set of tests involves the same kinds of basis-set convergence studies for the VIP and De values of As3 and As4 clusters. Both relativistic and nonrelativistic calculations are considered, including in each case both AE calculations and calculations with ECPs. Convergence and accuracy are assessed by comparing to relativistic AE calculations with the cc-pV5Z-DK or ma-cc-pV5Z-DK basis and to nonrelativistic AE calculations with the cc-pV5Z or ma-cc-pV5Z basis. The primary objective of this study is to evaluate the abilities of ECPs with both their recommended basis sets and other basis sets to reproduce the results of all-electron relativistic calculations. The performance of the def2 and ma series basis sets is consistent with their sizes, and quadruple-ζ basis sets are the best. The def2-TZVP basis set performs better than most of the 6-311G series basis sets, which are the most commonly used basis sets in the previous studies of arsenic compounds. However, relativistic def2-TZVP calculations are not recommended. The large-core ECPs, which are the only available ECPs for arsenic in the popular Gaussian program, have average errors of 9-12 kcal/mol for the arsenic systems studied; therefore, these ECPs are not recommended. The triple-ζ small-core relativistic ECP (RECP) basis set cc-pVTZ-PP is found to have performance better than that of the def2-TZVP

  10. Estimation of Evapotranspiration as a function of Photosynthetic Active Radiation

    NASA Astrophysics Data System (ADS)

    Wesley, E.; Migliaccio, K.; Judge, J.

    2012-12-01

    The purpose of this research project is to more accurately measure the water balance and energy movements to properly allocate water resources at the Snapper Creek Site in Miami-Dade County, FL, by quantifying and estimating evapotranspiration (ET). ET is generally estimated using weather based equations, this project focused on estimating ET as a function of Photosynthetic Active Radiation (PAR). The project objectives were first to compose a function of PAR and calculated coefficients that can accurately estimate daily ET values with the least amount of variables used in its estimation equation, and second, to compare the newly identified ET estimation PAR function to TURC estimations, in comparison to our actual Eddy Covariance (EC) ET data and determine the differences in ET values. PAR, volumetric water content (VWC), and temperature (T) data were quality checked and used in developing singular and multiple variable regression models fit with SigmaPlot software. Fifteen different ET estimation equations were evaluated against EC ET and TURC estimated ET using R2 and slope factors. The selected equation that best estimated EC ET was cross validated using a 5 month data set; its daily and monthly ET values and sums were compared against the commonly used TURC equation. Using a multiple variable regression model, an equation with three variables (i.e., VWC, T, and PAR) was identified that best fit EC ET daily data. However, a regression was also found that used only PAR and provided ET predictions of similar accuracy. The PAR based regression model predicted daily EC ET more accurately than the traditional TURC method. Using only PAR to estimate ET reduces the input variables as compared to using the TURC model which requires T and solar radiation. Thus, not only is the PAR approach more accurate but also more cost effective. The PAR-based ET estimation equation derived in this study may be over fit considering only 5 months of data were used to produce the PAR

  11. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

    PubMed

    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

  12. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  13. PREX1 Protein Function Is Negatively Regulated Downstream of Receptor Tyrosine Kinase Activation by p21-activated Kinases (PAKs).

    PubMed

    Barrows, Douglas; He, John Z; Parsons, Ramon

    2016-09-16

    Downstream of receptor tyrosine kinase and G protein-coupled receptor (GPCR) stimulation, the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchange factor (PREX) family of guanine nucleotide exchange factors (GEFs) activates Rho GTPases, leading to important roles for PREX proteins in numerous cellular processes and diseases, including cancer. PREX1 and PREX2 GEF activity is activated by the second messengers PIP3 and Gβγ, and further regulation of PREX GEF activity occurs by phosphorylation. Stimulation of receptor tyrosine kinases by neuregulin and insulin-like growth factor 1 (IGF1) leads to the phosphorylation of PREX1; however, the kinases that phosphorylate PREX1 downstream of these ligands are not known. We recently reported that the p21-activated kinases (PAKs), which are activated by GTP-bound Ras-related C3 botulinum toxin substrate 1 (Rac1), mediate the phosphorylation of PREX2 after insulin receptor activation. Here we show that certain phosphorylation events on PREX1 after insulin, neuregulin, and IGF1 treatment are PAK-dependent and lead to a reduction in PREX1 binding to PIP3 Like PREX2, PAK-mediated phosphorylation also negatively regulates PREX1 GEF activity. Furthermore, the onset of PREX1 phosphorylation was delayed compared with the phosphorylation of AKT, supporting a model of negative feedback downstream of PREX1 activation. We also found that the phosphorylation of PREX1 after isoproterenol and prostaglandin E2-mediated GPCR activation is partially PAK-dependent and likely also involves protein kinase A, which is known to reduce PREX1 function. Our data point to multiple mechanisms of PREX1 negative regulation by PAKs within receptor tyrosine kinase and GPCR-stimulated signaling pathways that have important roles in diseases such as diabetes and cancer. PMID:27481946

  14. EspC, an Autotransporter Protein Secreted by Enteropathogenic Escherichia coli, Causes Apoptosis and Necrosis through Caspase and Calpain Activation, Including Direct Procaspase-3 Cleavage

    PubMed Central

    Serapio-Palacios, Antonio

    2016-01-01

    ABSTRACT Enteropathogenic Escherichia coli (EPEC) has the ability to antagonize host apoptosis during infection through promotion and inhibition of effectors injected by the type III secretion system (T3SS), but the total number of these effectors and the overall functional relationships between these effectors during infection are poorly understood. EspC produced by EPEC cleaves fodrin, paxillin, and focal adhesion kinase (FAK), which are also cleaved by caspases and calpains during apoptosis. Here we show the role of EspC in cell death induced by EPEC. EspC is involved in EPEC-mediated cell death and induces both apoptosis and necrosis in epithelial cells. EspC induces apoptosis through the mitochondrial apoptotic pathway by provoking (i) a decrease in the expression levels of antiapoptotic protein Bcl-2, (ii) translocation of the proapoptotic protein Bax from cytosol to mitochondria, (iii) cytochrome c release from mitochondria to the cytoplasm, (iv) loss of mitochondrial membrane potential, (v) caspase-9 activation, (vi) cleavage of procaspase-3 and (vii) an increase in caspase-3 activity, (viii) PARP proteolysis, and (ix) nuclear fragmentation and an increase in the sub-G1 population. Interestingly, EspC-induced apoptosis was triggered through a dual mechanism involving both independent and dependent functions of its EspC serine protease motif, the direct cleavage of procaspase-3 being dependent on this motif. This is the first report showing a shortcut for induction of apoptosis by the catalytic activity of an EPEC protein. Furthermore, this atypical intrinsic apoptosis appeared to induce necrosis through the activation of calpain and through the increase of intracellular calcium induced by EspC. Our data indicate that EspC plays a relevant role in cell death induced by EPEC. PMID:27329750

  15. Characterizing cerebellar activity during autobiographical memory retrieval: ALE and functional connectivity investigations.

    PubMed

    Addis, Donna Rose; Moloney, Eleanor E J; Tippett, Lynette J; P Roberts, Reece; Hach, Sylvia

    2016-09-01

    Previous neuroimaging research has shown that the cerebellum is often activated during autobiographical memory (AM) retrieval. However, the reliability of that activation, its localization within the cerebellum, and its relationship to other areas of the AM network remains unknown. The current study used Activation Likelihood Estimation meta-analysis (ALE) as well as resting-state and task-related functional connectivity analyses to better characterize cerebellar activation in relation to AM. The ALE meta-analysis was run on 32 neuroimaging studies of AM retrieval. The results revealed a cluster of reliable AM-related activity within the Crus I lobule of the right posterior cerebellum. Using the peak ALE coordinate within Crus I as a seed region, both task-related and resting state functional connectivity analyses were run on fMRI data from 38 healthy participants. To determine the specificity of connectivity patterns to Crus I, we also included a cerebellar seed region in right Lobule VI previously identified in an ALE meta-analysis as associated with working memory. Resting-state functional connectivity analyses indicated that Crus I was intrinsically connected with other areas of the AM network as well as surrounding and contralateral cerebellar regions. In contrast, the Lobule VI seed was functionally connected with cerebral and cerebellar regions typically associated with working memory. The task-related connectivity analyses revealed a similar pattern, where the Crus I seed exhibited significant connectivity with key nodes of the AM network while the Lobule IV seed did not. During a semantic control task, both Crus I and Lobule VI showed significant correlations with a network of regions that was largely distinct from the AM network. Together these results indicate that right Crus I lobule is reliably engaged during AM retrieval and is functionally connected to the AM network both during rest, and more importantly, during AM retrieval. PMID:27235570

  16. Functional Magnetic Resonance Imaging for Imaging Neural Activity in the Human Brain: The Annual Progress

    PubMed Central

    Chen, Shengyong; Li, Xiaoli

    2012-01-01

    Functional magnetic resonance imaging (fMRI) is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area. PMID:22319550

  17. Functional magnetic resonance imaging for imaging neural activity in the human brain: the annual progress.

    PubMed

    Chen, Shengyong; Li, Xiaoli

    2012-01-01

    Functional magnetic resonance imaging (fMRI) is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area.

  18. Identifying functional subdivisions in the human brain using meta-analytic activation modeling-based parcellation.

    PubMed

    Yang, Yong; Fan, Lingzhong; Chu, Congying; Zhuo, Junjie; Wang, Jiaojian; Fox, Peter T; Eickhoff, Simon B; Jiang, Tianzi

    2016-01-01

    Parcellation of the human brain into fine-grained units by grouping voxels into distinct clusters has been an effective approach for delineating specific brain regions and their subregions. Published neuroimaging studies employing coordinate-based meta-analyses have shown that the activation foci and their corresponding behavioral categories may contain useful information about the anatomical-functional organization of brain regions. Inspired by these developments, we proposed a new parcellation scheme called meta-analytic activation modeling-based parcellation (MAMP) that uses meta-analytically obtained information. The raw meta data, including the experiments and the reported activation coordinates related to a brain region of interest, were acquired from the Brainmap database. Using this data, we first obtained the "modeled activation" pattern by modeling the voxel-wise activation probability given spatial uncertainty for each experiment that featured at least one focus within the region of interest. Then, we processed these "modeled activation" patterns across the experiments with a K-means clustering algorithm to group the voxels into different subregions. In order to verify the reliability of the method, we employed our method to parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation results were quite consistent with previous cytoarchitectonic and in vivo neuroimaging findings. Therefore, the MAMP proposed in the current study could be a useful complement to other methods for uncovering the functional organization of the human brain.

  19. Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans.

    PubMed Central

    Kniazeva, Marina; Sieber, Matt; McCauley, Scott; Zhang, Kang; Watts, Jennifer L; Han, Min

    2003-01-01

    While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans. PMID:12586704

  20. Functional Activation of the Flagellar Type III Secretion Export Apparatus

    PubMed Central

    Phillips, Andrew M.; Calvo, Rebecca A.; Kearns, Daniel B.

    2015-01-01

    Flagella are assembled sequentially from the inside-out with morphogenetic checkpoints that enforce the temporal order of subunit addition. Here we show that flagellar basal bodies fail to proceed to hook assembly at high frequency in the absence of the monotopic protein SwrB of Bacillus subtilis. Genetic suppressor analysis indicates that SwrB activates the flagellar type III secretion export apparatus by the membrane protein FliP. Furthermore, mutants defective in the flagellar C-ring phenocopy the absence of SwrB for reduced hook frequency and C-ring defects may be bypassed either by SwrB overexpression or by a gain-of-function allele in the polymerization domain of FliG. We conclude that SwrB enhances the probability that the flagellar basal body adopts a conformation proficient for secretion to ensure that rod and hook subunits are not secreted in the absence of a suitable platform on which to polymerize. PMID:26244495

  1. Functional characterization of alpha-synuclein protein with antimicrobial activity.

    PubMed

    Park, Seong-Cheol; Moon, Jeong Chan; Shin, Su Young; Son, Hyosuk; Jung, Young Jun; Kim, Nam-Hong; Kim, Young-Min; Jang, Mi-Kyeong; Lee, Jung Ro

    2016-09-16

    Alpha-synuclein (α-Syn), a small (14 kDa) protein associated with Parkinson's disease, is abundant in human neural tissues. α-Syn plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals; however, the mechanism by which it performs this function are not well understood. In addition, there is a correlation between α-Syn over-expression and upregulation of an innate immune response. Given the growing body of literature surrounding antimicrobial peptides (AMPs) in the brain, and the similarities between α-Syn and a previously characterized AMP, Amyloid-β, we set out to investigate if α-Syn shares AMP-like properties. Here we demonstrate that α-Syn exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, we demonstrate a role for α-Syn in inhibiting various pathogenic fungal strains such as Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani. We also analyzed localizations of recombinant α-Syn protein in E. coli and Candida albicans. These results suggest that in addition to α-Syn's role in neurotransmitter release, it appears to be a natural AMP. PMID:27520375

  2. Activated protein C: A regulator of human skin epidermal keratinocyte function.

    PubMed

    McKelvey, Kelly; Jackson, Christopher John; Xue, Meilang

    2014-05-26

    Activated protein C (APC) is a physiological anticoagulant, derived from its precursor protein C (PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor (EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  3. Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Introduction Neuropsychiatric manifestations are common in childhood-onset systemic lupus erythematosus (cSLE) and often include neurocognitive dysfunction (NCD). Functional magnetic resonance imaging (fMRI) can measure brain activation during tasks that invoke domains of cognitive function impaired by cSLE. This study investigates specific changes in brain function attributable to NCD in cSLE that have potential to serve as imaging biomarkers. Methods Formal neuropsychological testing was done to measure cognitive ability and to identify NCD. Participants performed fMRI tasks probing three cognitive domains impacted by cSLE: visuoconstructional ability (VCA), working memory, and attention. Imaging data, collected on 3-Tesla scanners, included a high-resolution T1-weighted anatomic reference image followed by a T2*-weighted whole-brain echo planar image series for each fMRI task. Brain activation using blood oxygenation level-dependent contrast was compared between cSLE patients with NCD (NCD-group, n = 7) vs. without NCD (noNCD-group, n = 14) using voxel-wise and region of interest-based analyses. The relationship of brain activation during fMRI tasks and performance in formal neuropsychological testing was assessed. Results Greater brain activation was observed in the noNCD-group vs. NCD-group during VCA and working memory fMRI tasks. Conversely, compared to the noNCD-group, the NCD-group showed more brain activation during the attention fMRI task. In region of interest analysis, brain activity during VCA and working memory fMRI tasks was positively associated with the participants' neuropsychological test performance. In contrast, brain activation during the attention fMRI task was negatively correlated with neuropsychological test performance. While the NCD group performed worse than the noNCD group during VCA and working memory tasks, the attention task was performed equally well by both groups. Conclusions NCD in patients with cSLE is characterized by

  4. CAST and ELKS proteins: structural and functional determinants of the presynaptic active zone.

    PubMed

    Hida, Yamato; Ohtsuka, Toshihisa

    2010-08-01

    Cytomatrix at the active zone-associated structural protein (CAST) was first purified from rat brain. It belongs to a protein family with the protein ELKS being its close relative. In nerve terminals, these proteins are specifically localized in the active zone (AZ). They have been shown to directly interact with other AZ proteins, including RIM1, Piccolo and Bassoon, and indirectly with Munc13-1 through RIM1, forming a large molecular complex at AZ. Moreover, the direct interaction of CAST with RIM1 and Bassoon appears to be involved in the release of neurotransmitters. However, it still remains elusive how CAST and ELKS regulate the assembly and function of AZ during synapse maturation. This review focuses on recent findings about the ELKS/CAST family revealed by biochemical strategies and genetic studies, and discusses the potential roles of this protein family in the function and organization of the presynaptic AZ.

  5. Applying the Model of Goal-Directed Behavior, Including Descriptive Norms, to Physical Activity Intentions: A Contribution to Improving the Theory of Planned Behavior.

    PubMed

    Esposito, Gabriele; van Bavel, René; Baranowski, Tom; Duch-Brown, Néstor

    2016-08-01

    The theory of planned behavior (TPB) has received its fair share of criticism lately, including calls for it to retire. We contribute to improving the theory by testing extensions such as the model of goal-directed behavior (MGDB, which adds desire and anticipated positive and negative emotions) applied to physical activity (PA) intention. We also test the inclusion of a descriptive norms construct as an addition to the subjective norms construct, also applied to PA, resulting in two additional models: TPB including descriptive norms (TPB + DN) and MGDB including descriptive norms (MGDB + DN). The study is based on an online survey of 400 young adult Internet users, previously enrolled in a subject pool. Confirmatory factor analysis (CFA) showed that TPB and TPB + DN were not fit for purpose, while MGDB and MGDB + DN were. Structural equation modelling (SEM) conducted on MGDB and MGDB + DN showed that the inclusion of descriptive norms took over the significance of injunctive norms, and increased the model's account of total variance in intention to be physically active. PMID:27229344

  6. Fluorescence-activated sorting of rat hepatocytes based on their mixed function oxidase activities towards diethoxyfluorescein.

    PubMed Central

    White, I N; Green, M L; Legg, R F

    1987-01-01

    The formation of ethoxyfluorescein and fluorescein from diethoxyfluorescein by isolated rat hepatocytes has been used as a basis for separating such cells dependent on their mixed function oxidase activities by fluorescence-activated flow cytometry. Five equal fractions defined by computer-generated regions were isolated. Non-viable cells with low fluorescence (region 1) represented 10-15% of the population, while the remainder with higher mixed function oxidase activities (regions 2-5), were greater than 95% viable by Trypan Blue exclusion. In region 1, 30% of the viable cells were binucleate, 67% diploid while in region 5, 13% were binucleate and 69% tetraploid. At 3 h after sorting, following attachment to glass coverslips, exposure of cells to methyl methanesulphonate, retrorsine or norethindrone resulted in unscheduled DNA synthesis which was 2-fold higher in the tetraploid-rich region 5, while aflatoxin B1, benzo[a]pyrene or 2-acetylaminofluorene caused a 5-fold increase in unscheduled DNA synthesis in these cells, relative to the diploid-rich hepatocytes in region 2. Images Fig. 4. PMID:3689348

  7. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments

    PubMed Central

    Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

    2016-01-01

    Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

  8. The relation of childhood physical activity and aerobic fitness to brain function and cognition: a review.

    PubMed

    Khan, Naiman A; Hillman, Charles H

    2014-05-01

    Physical inactivity has been shown to increase the risk for several chronic diseases across the lifespan. However, the impact of physical activity and aerobic fitness on childhood cognitive and brain health has only recently gained attention. The purposes of this article are to: 1) highlight the recent emphasis for increasing physical activity and aerobic fitness in children's lives for cognitive and brain health; 2) present aspects of brain development and cognitive function that are susceptible to physical activity intervention; 3) review neuroimaging studies examining the cross-sectional and experimental relationships between aerobic fitness and executive control function; and 4) make recommendations for future research. Given that the human brain is not fully developed until the third decade of life, preadolescence is characterized by changes in brain structure and function underlying aspects of cognition including executive control and relational memory. Achieving adequate physical activity and maintaining aerobic fitness in childhood may be a critical guideline to follow for physical as well as cognitive and brain health.

  9. Reconstructing ecosystem functions of the active microbial community of the Baltic Sea oxygen depleted sediments.

    PubMed

    Thureborn, Petter; Franzetti, Andrea; Lundin, Daniel; Sjöling, Sara

    2016-01-01

    Baltic Sea deep water and sediments hold one of the largest anthropogenically induced hypoxic areas in the world. High nutrient input and low water exchange result in eutrophication and oxygen depletion below the halocline. As a consequence at Landsort Deep, the deepest point of the Baltic Sea, anoxia in the sediments has been a persistent condition over the past decades. Given that microbial communities are drivers of essential ecosystem functions we investigated the microbial community metabolisms and functions of oxygen depleted Landsort Deep sediments by metatranscriptomics. Results show substantial expression of genes involved in protein metabolism demonstrating that the Landsort Deep sediment microbial community is active. Identified expressed gene suites of metabolic pathways with importance for carbon transformation including fermentation, dissimilatory sulphate reduction and methanogenesis were identified. The presence of transcripts for these metabolic processes suggests a potential for heterotrophic-autotrophic community synergism and indicates active mineralisation of the organic matter deposited at the sediment as a consequence of the eutrophication process. Furthermore, cyanobacteria, probably deposited from the water column, are transcriptionally active in the anoxic sediment at this depth. Results also reveal high abundance of transcripts encoding integron integrases. These results provide insight into the activity of the microbial community of the anoxic sediment at the deepest point of the Baltic Sea and its possible role in ecosystem functioning. PMID:26823996

  10. TMJ function after partial condylectomy in active mandibular condylar hyperplasia

    PubMed Central

    Olate, Sergio; Martinez, Felipe; Uribe, Francisca; Pozzer, Leandro; Cavalieri-Pereira, Lucas; de Moraes, Marcio

    2014-01-01

    Condylar hyperplasia is a frequent pathology that causes severe facial asymmetries. The partial condylectomy generally halts the disease. The aim of this research was to examine post-condylectomy TMJ function; 14 patients were included in this study, 6 male and 8 female. The average age was 21 years old. In all, the partial condylectomy was performed with preauricular or endaural access and the osteotomy were performed with drills, saw or an ultrasonic system. The patients were assessed with 3 or more time after surgery and were considering maximum mouth opening, right and left lateralities, presence of pain, noises, alterations in the facial nerve (VII) and esthetic alteration from the scar. The analysis was performed with the visual analog scale (VAS) and with a 7 cm metallic rule. Data analysis was descriptive plus chi-square test considering p value < 0.05 for statistical differences. With an average of 11 month after surgery, the results showed that the open mouth (over 35 mm) and lateralities (average 9 mm for the both right and left side) were normal and without statistical differences between the right or left side. Noise was observed in 3 patients and pain was observed in two patients with level 2 and 1 (VAS score). Scar was not related to problem with patient and the temporal branch of facial nerve was observed with limitations but without problem for patients. It can be concluded that the condylectomy is a safe and effective procedure with low morbidity for patients. PMID:24753777

  11. TMJ function after partial condylectomy in active mandibular condylar hyperplasia.

    PubMed

    Olate, Sergio; Martinez, Felipe; Uribe, Francisca; Pozzer, Leandro; Cavalieri-Pereira, Lucas; de Moraes, Marcio

    2014-01-01

    Condylar hyperplasia is a frequent pathology that causes severe facial asymmetries. The partial condylectomy generally halts the disease. The aim of this research was to examine post-condylectomy TMJ function; 14 patients were included in this study, 6 male and 8 female. The average age was 21 years old. In all, the partial condylectomy was performed with preauricular or endaural access and the osteotomy were performed with drills, saw or an ultrasonic system. The patients were assessed with 3 or more time after surgery and were considering maximum mouth opening, right and left lateralities, presence of pain, noises, alterations in the facial nerve (VII) and esthetic alteration from the scar. The analysis was performed with the visual analog scale (VAS) and with a 7 cm metallic rule. Data analysis was descriptive plus chi-square test considering p value < 0.05 for statistical differences. With an average of 11 month after surgery, the results showed that the open mouth (over 35 mm) and lateralities (average 9 mm for the both right and left side) were normal and without statistical differences between the right or left side. Noise was observed in 3 patients and pain was observed in two patients with level 2 and 1 (VAS score). Scar was not related to problem with patient and the temporal branch of facial nerve was observed with limitations but without problem for patients. It can be concluded that the condylectomy is a safe and effective procedure with low morbidity for patients. PMID:24753777

  12. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    PubMed Central

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  13. The orexin neuropeptide system: physical activity and hypothalamic function throughout the aging process

    PubMed Central

    Zink, Anastasia N.; Perez-Leighton, Claudio Esteban; Kotz, Catherine M.

    2014-01-01

    There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1) How do orexin peptides modulate physical activity? (2) What are the effects of aging and lifestyle choices on physical activity? (3) What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes. PMID:25408639

  14. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults

    PubMed Central

    Cheng, Dominic T.; Meintjes, Ernesta M.; Stanton, Mark E.; Desmond, John E.; Pienaar, Mariska; Dodge, Neil C.; Power, John M.; Molteno, Christopher D.; Disterhoft, John F.; Jacobson, Joseph L.; Jacobson, Sandra W.

    2013-01-01

    This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I– II, lateral lobules IV–IX, and vermis IV–VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during eyeblink classical conditioning. PMID:23674498

  15. Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults.

    PubMed

    Cheng, Dominic T; Meintjes, Ernesta M; Stanton, Mark E; Desmond, John E; Pienaar, Mariska; Dodge, Neil C; Power, John M; Molteno, Christopher D; Disterhoft, John F; Jacobson, Joseph L; Jacobson, Sandra W

    2014-04-01

    This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC.

  16. Sequential muscle activity and its functional role in the upper extremity and trunk during overarm throwing.

    PubMed

    Hirashima, Masaya; Kadota, Hiroshi; Sakurai, Shizuka; Kudo, Katzutoshi; Ohtsuki, Tatsuyuki

    2002-04-01

    The proximal-to-distal segmental sequence has been identified in many sports activities, including baseball pitching and ball kicking. However, proximal-to-distal sequential muscle activity has not been identified. The aims of this study were to establish whether sequential muscle activity does occur and, if it does, to determine its functional role. We recorded surface electromyograms (EMGs) for 17 muscles from the upper extremity and abdomen during overarm throwing and detected the onset and peak times as indices of muscle activity. The following electromyographic properties were commonly identified in the participants. First, sequential muscle activity was observed from the scapular protractors to the shoulder horizontal flexors and from the shoulder horizontal flexors to the elbow extensor, but not from the elbow extensor to the wrist flexor or forearm pronator. Secondly, the external oblique contralateral to the throwing arm became activated before the ipsilateral external oblique. This sequence is considered to be very effective for the generation of high force and energy in the trunk. Thirdly, the ipsilateral external oblique began its activity almost at foot strike. Finally, the main activity of the rectus abdominis appeared just before the point of release.

  17. Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.

    PubMed

    Bhat, Zeenat Yousuf; Bostwick, David G; Hossain, Deloar; Zeng, Xu

    2014-07-01

    Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts. PMID:24684655

  18. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus.

    PubMed

    Patel, Kalyani R; Chernock, Rebecca D; Zhang, Tian R; Wang, Xiaowei; El-Mofty, Samir K; Lewis, James S

    2013-11-01

    Most oropharyngeal squamous cell carcinomas (SCC) and histologic variants harbor transcriptionally active human papillomavirus (HPV). While HPV DNA can be found in many non-oropharyngeal head and neck carcinomas, transcriptionally active HPV is rare. Verrucous carcinoma is a variant with bland cytology, warty appearance, locally destructive growth, and lack of metastasis when lacking a frankly invasive carcinoma component. Studies have shown variable rates of HPV DNA and p16 protein expression in such tumors but still have not clearly addressed if the virus has biological activity or clinical relevance in the positive cases. Department files were searched for verrucous neoplasms, including pure verrucous carcinoma, verrucous carcinoma with dysplasia or minimal invasion, and SCC arising in verrucous carcinoma (ie, having a major component of frankly invasive carcinoma). p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR) and E6/E7 mRNA reverse transcription PCR for high-risk HPV types were performed. Of the 49 cases, 6 (12.2%) showed strong (>50%) staining for p16. HPV DNA was detected in 7/49 (14.3%) cases, but only one case was positive for both p16, and HPV DNA. A total of 36 cases yielded sufficient RNA for RT-PCR (18 verrucous carcinomas, 13 atypical verrucous carcinomas, and 5 SCC arising in verrucous carcinoma). All 36 were negative, including the four p16-positive and three HPV DNA-positive tumors tested. Although a minority of verrucous carcinoma lesions are p16 and HPV DNA positive, transcriptionally active high-risk HPV is uniformly absent. These findings argue that verrucous carcinoma and its related squamous cell carcinomas are not HPV-driven tumors.

  19. Antioxidant Effect of Melatonin on the Functional Activity of Colostral Phagocytes in Diabetic Women

    PubMed Central

    Fagundes, Danny L. G.; Calderon, Iracema M. P.; França, Eduardo L.

    2013-01-01

    Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca2+ release. Phagocytes treated with TMB-8 (intracellular Ca2+ inhibitor) decreased superoxide, bactericidal activity and intracellular Ca2+ release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against EPEC

  20. Structure and Function of the 5'-<' Exoribonuclease Rat1 and its Activating Partner Rai1

    SciTech Connect

    Xiang, S.; Cooper-Morgan, A; Jiao, X; Kiledjian, M; Manley, J; Tong, L

    2009-01-01

    The 5??3? exoribonucleases (XRNs) comprise a large family of conserved enzymes in eukaryotes with crucial functions in RNA metabolism and RNA interference1, 2, 3, 4, 5. XRN2, or Rat1 in yeast6, functions primarily in the nucleus and also has an important role in transcription termination by RNA polymerase II (refs 7-14). Rat1 exoribonuclease activity is stimulated by the protein Rai1 (refs 15, 16). Here we report the crystal structure at 2.2 A resolution of Schizosaccharomyces pombe Rat1 in complex with Rai1, as well as the structures of Rai1 and its murine homologue Dom3Z alone at 2.0 A resolution. The structures reveal the molecular mechanism for the activation of Rat1 by Rai1 and for the exclusive exoribonuclease activity of Rat1. Biochemical studies confirm these observations, and show that Rai1 allows Rat1 to degrade RNAs with stable secondary structure more effectively. There are large differences in the active site landscape of Rat1 compared to related and PIN (PilT N terminus) domain-containing nucleases17, 18, 19, 20. Unexpectedly, we identified a large pocket in Rai1 and Dom3Z that contains highly conserved residues, including three acidic side chains that coordinate a divalent cation. Mutagenesis and biochemical studies demonstrate that Rai1 possesses pyrophosphohydrolase activity towards 5? triphosphorylated RNA. Such an activity is important for messenger RNA degradation in bacteria21, but this is, to our knowledge, the first demonstration of this activity in eukaryotes and suggests that Rai1/Dom3Z may have additional important functions in RNA metabolism.

  1. Optical modulator including grapene

    DOEpatents

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  2. [Effect of physical activity on age involution of functional abilities of humans].

    PubMed

    Miskotnykh, V V; Khodasevich, L S; Mel'tser, V L

    2012-01-01

    A survey of 433 healthy, mature- and middle-aged men with different modes of habitual daily physical activity was made. Depending on the modes of motor activity all the surveyed were divided into 4 groups, each of which has been ranked by the ten-year age interval. The assessment of functional status using automated hardware-software complex "AMSAT-Covert" to determine the level of maximum oxygen consumption, lipid peroxidation and activity of the antioxidant defense system was performed. Results of the study enabled the authors to formulate a provision under which to extend the period of active, creative longevity and increased life expectancy we need to review the approaches to the regulation of physical activity by rationally constructed motor mode as part of a comprehensive system of health protection. Exercises, not increasing the requirements to the functionality involved and not causing physiological changes should be included in the recommended motor mode, which are incomparably less than officially accepted in modern practice fitness training.

  3. Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

    PubMed

    McCormack, K M; Kluwe, W M; Sanger, V L; Hook, J B

    1978-04-01

    Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function. PMID:209969

  4. A density functional theory model of mechanically activated silyl ester hydrolysis

    SciTech Connect

    Pill, Michael F.; Schmidt, Sebastian W.; Beyer, Martin K.; Clausen-Schaumann, Hauke; Kersch, Alfred

    2014-01-28

    To elucidate the mechanism of the mechanically activated dissociation of chemical bonds between carboxymethylated amylose (CMA) and silane functionalized silicon dioxide, we have investigated the dissociation kinetics of the bonds connecting CMA to silicon oxide surfaces with density functional calculations including the effects of force, solvent polarizability, and pH. We have determined the activation energies, the pre-exponential factors, and the reaction rate constants of candidate reactions. The weakest bond was found to be the silyl ester bond between the silicon and the alkoxy oxygen atom. Under acidic conditions, spontaneous proton addition occurs close to the silyl ester such that neutral reactions become insignificant. Upon proton addition at the most favored position, the activation energy for bond hydrolysis becomes 31 kJ mol{sup −1}, which agrees very well with experimental observation. Heterolytic bond scission in the protonated molecule has a much higher activation energy. The experimentally observed bi-exponential rupture kinetics can be explained by different side groups attached to the silicon atom of the silyl ester. The fact that different side groups lead to different dissociation kinetics provides an opportunity to deliberately modify and tune the kinetic parameters of mechanically activated bond dissociation of silyl esters.

  5. Theoretical study of the adsorption of aromatic units on carbon allotropes including explicit (empirical) DFT dispersion corrections and implicitly dispersion-corrected functionals: the pyridine case.

    PubMed

    Ramos-Berdullas, Nicolás; Pérez-Juste, Ignacio; Van Alsenoy, Christian; Mandado, Marcos

    2015-01-01

    The suitability of implicitly dispersion-corrected functionals, namely the M06-2X, for the determination of interaction energies and electron polarization densities in adsorption studies of aromatic molecules on carbon allotropes surfaces is analysed by comparing the results with those obtained using explicit dispersion through Grimme's empirical corrections. Several models of increasing size for the graphene sheet together with one-dimensional curved carbon structures, (5,5), (6,6) and (7,7) armchair single-walled nanotubes, and two-dimensional curved carbon structures, C60 fullerene, have been considered as substrates in this work, whereas pyridine has been chosen as an example for the adsorbed aromatic molecule. Comparison with recent experimental estimations of the adsorption energy and calculations using periodic boundary conditions on a supercell of 72 carbon atoms indicates that a finite model containing ninety six carbon atoms (C96) approaches quite well the adsorption on a graphene sheet. Analysis of the interaction energy components reveals that the M06-2X functional accounts for most of the dispersion energy implicitly, followed far by wB97X and B3LYP, whereas B97 and BLYP do not differ too much from HF. It has been found that M06-2X corrects only the energy component associated to dispersion and leaves the rest, electrostatic, Pauli and induction "unaltered" with respect to the other DFT functionals investigated. Moreover, only the M06-2X functional reflects the effect of dispersion on the electron polarization density, whereas for the remaining functionals the polarization density does not differ too much from the HF density. This makes the former functional more suitable a priori for the calculation of electron density related properties in these adsorption complexes.

  6. Multi-substrate-activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality.

    PubMed

    Mannervik, Bengt; Runarsdottir, Arna; Kurtovic, Sanela

    2009-08-01

    A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate-activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the 'best' variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.

  7. Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

    PubMed

    Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

    2014-08-01

    Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.

  8. Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates

    PubMed Central

    Pfaller, Michael A.; Messer, Shawn A.; Rhomberg, Paul R.; Jones, Ronald N.; Castanheira, Mariana

    2016-01-01

    Objectives The objective of this study was to evaluate the in vitro activity of CD101, a novel echinocandin with a long serum elimination half-life, and comparator (anidulafungin and caspofungin) antifungal agents against a collection of Candida and Aspergillus spp. isolates. Methods CD101 and comparator agents were tested against 106 Candida spp. and 67 Aspergillus spp. isolates, including 27 isolates of Candida harbouring fks hotspot mutations and 12 itraconazole non-WT Aspergillus, using CLSI and EUCAST reference susceptibility broth microdilution (BMD) methods. Results Against WT and fks mutant Candida albicans, Candida glabrata and Candida tropicalis, the activity of CD101 [MIC90 = 0.06, 0.12 and 0.03 mg/L, respectively (CLSI method values)] was comparable to that of anidulafungin (MIC90 = 0.03, 0.12 and 0.03 mg/L, respectively) and caspofungin (MIC90 = 0.12, 0.25 and 0.12 mg/L, respectively). WT Candida krusei isolates were very susceptible to CD101 (MIC = 0.06 mg/L). CD101 activity (MIC50/90 = 1/2 mg/L) was comparable to that of anidulafungin (MIC50/90 = 2/2 mg/L) against Candida parapsilosis. CD101 (MIC mode = 0.06 mg/L for C. glabrata) was 2- to 4-fold more active against fks hotspot mutants than caspofungin (MIC mode = 0.5 mg/L). CD101 was active against Aspergillus fumigatus, Aspergillus terreus, Aspergillus niger and Aspergillus flavus (MEC90 range = ≤0.008–0.03 mg/L). The essential agreement between CLSI and EUCAST methods for CD101 was 92.0%–100.0% among Candida spp. and 95.0%–100.0% among Aspergillus spp. Conclusions The activity of CD101 is comparable to that of other members of the echinocandin class for the prevention and treatment of serious fungal infections. Similar results for CD101 activity versus Candida and Aspergillus spp. may be obtained with either CLSI or EUCAST BMD methods. PMID:27287236

  9. Effects of soil type and farm management on soil ecological functional genes and microbial activities

    SciTech Connect

    Reeve, Jennifer; Schadt, Christopher Warren; Carpenter-Boggs, Lynne; Kang, S.; Zhou, Jizhong; Reganold, John P.

    2010-01-01

    Relationships between soil microbial diversity and soil function are the subject of much debate. Process-level analyses have shown that microbial function varies with soil type and responds to soil management. However, such measurements cannot determine the role of community structure and diversity in soil function. The goal of this study was to investigate the role of gene frequency and diversity, measured by microarray analysis, on soil processes. The study was conducted in an agro-ecosystem characterized by contrasting management practices and soil types. Eight pairs of adjacent commercial organic and conventional strawberry fields were matched for soil type, strawberry variety, and all other environmental conditions. Soil physical, chemical and biological analyses were conducted including functional gene microarrays (FGA). Soil physical and chemical characteristics were primarily determined by soil textural type (coarse vs fine-textured), but biological and FGA measures were more influenced by management (organic vs conventional). Organically managed soils consistently showed greater functional activity as well as FGA signal intensity (SI) and diversity. Overall FGA SI and diversity were correlated to total soil microbial biomass. Functional gene group SI and/or diversity were correlated to related soil chemical and biological measures such as microbial biomass, cellulose, dehydrogenase, ammonium and sulfur. Management was the dominant determinant of soil biology as measured by microbial gene frequency and diversity, which paralleled measured microbial processes.

  10. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes.

    PubMed

    Blaker-Lee, Alicia; Gupta, Sunny; McCammon, Jasmine M; De Rienzo, Gianluca; Sive, Hazel

    2012-11-01

    Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs), intellectual disability disorder (IDD) and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV). The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed 'dosage sensors'), which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development - impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa) and kinesin family member 22 (kif22) genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least) two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD. PMID:22566537

  11. Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism.

    PubMed

    Spencer, Michael D; Holt, Rosemary J; Chura, Lindsay R; Calder, Andrew J; Suckling, John; Bullmore, Edward T; Baron-Cohen, Simon

    2012-11-01

    Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others.

  12. High-throughput functional comparison of promoter and enhancer activities.

    PubMed

    Nguyen, Thomas A; Jones, Richard D; Snavely, Andrew R; Pfenning, Andreas R; Kirchner, Rory; Hemberg, Martin; Gray, Jesse M

    2016-08-01

    Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is not due to conventional core promoter elements or splicing signals. Instead, we find that particular transcription factor binding motifs are intrinsically biased toward the generation of promoter activity, whereas others are not. Although the specific biases we observe may be dependent on experimental or cellular context, our results suggest that gene promoters are distinguished from distal enhancers by specific complements of transcriptional activators. PMID:27311442

  13. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    PubMed

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p < 0.001). This study demonstrates an abnormal pattern of brain activation in secondary motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  14. Pig skin includes dendritic cell subsets transcriptomically related to human CD1a and CD14 dendritic cells presenting different migrating behaviors and T cell activation capacities.

    PubMed

    Marquet, Florian; Vu Manh, Thien-Phong; Maisonnasse, Pauline; Elhmouzi-Younes, Jamila; Urien, Céline; Bouguyon, Edwige; Jouneau, Luc; Bourge, Mickael; Simon, Gaëlle; Ezquerra, Angel; Lecardonnel, Jérôme; Bonneau, Michel; Dalod, Marc; Schwartz-Cornil, Isabelle; Bertho, Nicolas

    2014-12-15

    Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the human CD1a(pos) DDC. CD163(low) DDC migrate toward CCL21, they activate allogeneic CD8 and CD4 T cells and, like their potential human lung counterpart, they skew CD4 T cells toward a Th17 profile. We thus conclude that swine skin is a relevant model for human skin vaccination.

  15. Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4.

    PubMed

    Ko, M S H

    2016-01-01

    Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities. PMID:27475850

  16. Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4.

    PubMed

    Ko, M S H

    2016-01-01

    Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities.

  17. Three homologues, including two membrane-bound proteins, of the disulfide oxidoreductase DsbA in Neisseria meningitidis: effects on bacterial growth and biogenesis of functional type IV pili.

    PubMed

    Tinsley, Colin R; Voulhoux, Romé; Beretti, Jean-Luc; Tommassen, Jan; Nassif, Xavier

    2004-06-25

    Many proteins, especially membrane and exported proteins, are stabilized by intramolecular disulfide bridges between cysteine residues without which they fail to attain their native functional conformation. The formation of these bonds is catalyzed in Gram-negative bacteria by enzymes of the Dsb system. Thus, the activity of DsbA has been shown to be necessary for many phenotypes dependent on exported proteins, including adhesion, invasion, and intracellular survival of various pathogens. The Dsb system in Neisseria meningitidis, the causative agent of cerebrospinal meningitis, has not, however, been studied. In a previous work where genes specific to N. meningitidis and not present in the other pathogenic Neisseria were isolated, a meningococcus-specific dsbA gene was brought to light (Tinsley, C. R., and Nassif, X. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11109-11114). Inactivation of this gene, however, did not result in deficits in the phenotypes commonly associated with DsbA. A search of available genome data revealed that the meningococcus contains three dsbA genes encoding proteins with different predicted subcellular locations, i.e. a soluble periplasmic enzyme and two membrane-bound lipoproteins. Cell fractionation experiments confirmed the localization in the inner membrane of the latter two, which include the previously identified meningococcus-specific enzyme. Mutational analysis demonstrated that the deletion of any single enzyme was compensated by the action of the remaining two on bacterial growth, whereas the triple mutant was unable to grow at 37 degrees C. Remarkably, however, the combined absence of the two membrane-bound enzymes led to a phenotype of sensitivity to reducing agents and loss of functionality of the pili. Although in many species a single periplasmic DsbA is sufficient for the correct folding of various proteins, in the meningococcus a membrane-associated DsbA is required for a wild type DsbA+ phenotype even in the presence of a

  18. Stages of change for physical activity and dietary habits in persons with type 2 diabetes included in a mobile health intervention: the Norwegian study in RENEWING HEALTH

    PubMed Central

    Holmen, Heidi; Wahl, Astrid; Torbjørnsen, Astrid; Jenum, Anne Karen; Småstuen, Milada Cvancarova; Ribu, Lis

    2016-01-01

    Objective The aim of this study was to investigate stages of change for physical activity and dietary habits using baseline data from persons with type 2 diabetes included in a mobile health intervention. We examined the associations between stages of change for physical activity change and dietary change, and between stages of change for each behavior and individual characteristics, health-related quality of life, self-management, depressive symptoms, and lifestyle. Research design and methods We examined 151 persons with type 2 diabetes with an glycated hemoglobin (HbA1c) level ≥7.1%, aged ≥18 years at baseline of a randomized controlled trial, before testing a mobile app with or without health counseling. Stages of change were dichotomized into ‘pre-action’ and ‘action’. Self-management was measured using the Health Education Impact Questionnaire (heiQ) where a higher score reflects increased self-management, and health-related quality of life was measured with the Short-Form-36 (SF-36). Logistic regression modeling was performed. Results The median HbA1c level was 7.9% (7.1–12.4), 90% were overweight or obese, and 20% had ≥3 comorbidities. 58% were in the preaction stage for physical activity change and 79% in the preaction stage for dietary change. Higher scores of self-management were associated with an increased chance of being in the action stage for both dietary change and physical activity change. Higher body mass index was associated with an 8% reduced chance of being in the action stage for physical activity change (OR 0.92, 95% CI 0.86 to 0.99). Conclusions Being in the action stage was associated with higher scores of self-management, crucial for type 2 diabetes. Over half of the participants were in the preaction stage for physical activity and dietary change, and many had a high disease burden with comorbidities and overweight. Trial registration number NCT01315756. PMID:27239317

  19. 20 CFR 667.220 - What Workforce Investment Act title I functions and activities constitute the costs of...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cash management functions; (ii) Procurement and purchasing functions; (iii) Property management functions; (iv) Personnel management functions; (v) Payroll functions; (vi) Coordinating the resolution of... functions and activities constitute the costs of administration subject to the administrative cost...

  20. Development of new auxiliary basis functions of the Karlsruhe segmented contracted basis sets including diffuse basis functions (def2-SVPD, def2-TZVPPD, and def2-QVPPD) for RI-MP2 and RI-CC calculations.

    PubMed

    Hellweg, Arnim; Rappoport, Dmitrij

    2015-01-14

    We report optimized auxiliary basis sets for use with the Karlsruhe segmented contracted basis sets including moderately diffuse basis functions (Rappoport and Furche, J. Chem. Phys., 2010, 133, 134105) in resolution-of-the-identity (RI) post-self-consistent field (post-SCF) computations for the elements H-Rn (except lanthanides). The errors of the RI approximation using optimized auxiliary basis sets are analyzed on a comprehensive test set of molecules containing the most common oxidation states of each element and do not exceed those of the corresponding unaugmented basis sets. During these studies an unsatisfying performance of the def2-SVP and def2-QZVPP auxiliary basis sets for Barium was found and improved sets are provided. We establish the versatility of the def2-SVPD, def2-TZVPPD, and def2-QZVPPD basis sets for RI-MP2 and RI-CC (coupled-cluster) energy and property calculations. The influence of diffuse basis functions on correlation energy, basis set superposition error, atomic electron affinity, dipole moments, and computational timings is evaluated at different levels of theory using benchmark sets and showcase examples.

  1. Functional Mapping of Protein Kinase A Reveals Its Importance in Adult Schistosoma mansoni Motor Activity

    PubMed Central

    de Saram, Paulu S. R.; Ressurreição, Margarida; Davies, Angela J.; Rollinson, David; Emery, Aidan M.; Walker, Anthony J.

    2013-01-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and ‘smart’ anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology

  2. Functional mapping of protein kinase A reveals its importance in adult Schistosoma mansoni motor activity.

    PubMed

    de Saram, Paulu S R; Ressurreição, Margarida; Davies, Angela J; Rollinson, David; Emery, Aidan M; Walker, Anthony J

    2013-01-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and 'smart' anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology.

  3. Are Functional and Activity Limitations Becoming More Prevalent among 55 to 69-Year-Olds in the United States?

    PubMed Central

    Choi, HwaJung; Schoeni, Robert F.; Martin, Linda G.

    2016-01-01

    Objectives This study examines changes in functional and activity limitations 1998–2012 for individuals 55–69. Methods Logistic models are used to estimate trends in limitations in vision, hearing, physical and cognitive functioning, IADLs, and ADLs. Additional models assess the extent to which trends are associated with and differ by education, smoking, and BMI. Results Changes in prevalence of limitations in vision, hearing, cognitive functioning, and ADLs are not statistically significant. Limitations in physical functioning declined by 0.37% per year. IADL limitations increased by 1.33% per year, but most of the increase occurred between 2008 and 2010/2012, and are associated with economic hardship during the Great Recession. Increases in education are especially beneficially associated with trends in limitations, but reductions in smoking also appear to be advantageous for some outcomes. Increases in BMI are associated with trends in physical functioning, IADL, and ADL limitation. Discussion For Americans 55–69, functional and activity limitations were largely unchanged 1998–2012. Our results suggest that if educational attainment had not increased, most functional and activity limitations potentially could have worsened substantially. Future change in educational attainment is not expected to be so positive. Continued monitoring of trends in activity limitations might well include greater focus on the explanatory roles of environmental factors, including economic circumstances. PMID:27783638

  4. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function

    PubMed Central

    Cai, Weili; Wei, Youheng; Jarnik, Michal; Reich, John; Lilly, Mary A.

    2016-01-01

    TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans. Here we define the in vivo role of the GATOR2 component Wdr24 in Drosophila. Using a combination of genetic, biochemical, and cell biological techniques we demonstrate that Wdr24 has both TORC1 dependent and independent functions in the regulation of cellular metabolism. Through the characterization of a null allele, we show that Wdr24 is a critical effector of the GATOR2 complex that promotes the robust activation of TORC1 and cellular growth in a broad array of Drosophila tissues. Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. Notably, we find that two additional members of the GATOR2 complex, Mio and Seh1, also have a TORC1 independent role in the regulation of lysosome function. These findings represent a surprising and previously unrecognized function of GATOR2 complex components in the regulation of lysosomes. Consistent with our findings in Drosophila, through the characterization of a wdr24-/- knockout HeLa cell line we determined that Wdr24 promotes lysosome acidification and autophagic flux in mammalian cells. Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes. PMID:27166823

  5. Activity limitations and participation restrictions in women with hand osteoarthritis: patients' descriptions and associations between dimensions of functioning

    PubMed Central

    Kjeken, I; Dagfinrud, H; Slatkowsky-Christ..., B; Mowinckel, P; Uhlig, T; Kvien, T; Finset, A

    2005-01-01

    Objective: To describe the functional consequences of hand osteoarthritis, and analyse associations between personal factors, hand impairment, activity limitations, and participation restrictions within the framework of the International Classification of Functioning (ICF). Methods: 87 women with hand osteoarthritis completed a clinical examination including recording of sociodemographic data, measures of hand impairment, and completion of self reported health status measures. The function subscale of the AUSCAN Osteoarthritis Hand Index was used as a measure of hand related activity limitations, while the Canadian Occupational Performance Measure (COPM) was used to describe and measure activity limitations and participation restrictions as perceived by the individual. The study variables were categorised using the dimensions in the ICF framework and analysed using bivariate and multivariate statistical approaches. Results: The patients described problems in many domains of activity and participation. The most frequently described hand related problems were activities requiring considerable grip strength combined with twisting of the hands. On the impairment level, the patients had reduced grip force and joint mobility in the hands, and resisted motion was painful. Regression analyses showed that hand related activity limitations were associated with measures of hand impairment, while activity and participation (as measured by the COPM) were more strongly associated with personal factors than with hand impairment. Conclusions: Hand osteoarthritis has important functional consequences in terms of pain, reduced hand mobility and grip force, activity limitations, and participation restrictions. Rehabilitation programmes should therefore be multidisciplinary and multidimensional, focusing on hand function, occupational performance, and coping strategies. PMID:15829571

  6. The Contribution of Executive Functions to Participation in School Activities of Children with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Zingerevich, Chaya; Patricia D., LaVesser

    2009-01-01

    This study describes the contribution of executive functions to participation in school activities of children diagnosed with ASD ages 6-9 years while controlling for sensory processing. Twenty-four children, ages 73-112 months (S.D. = 11.4), diagnosed with high functioning ASD were assessed with the Wisconsin Card Sorting Test. Their teachers…

  7. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

    SciTech Connect

    Muszbek, L.; Adany, R.; Mikkola, H.

    1996-10-01

    Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 2} antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored. 328 refs., 4 figs.

  8. Optochemical Activation of Kinase Function in Live Cells

    PubMed Central

    Karginov, Andrei V.; Hahn, Klaus M.; Deiters, Alexander

    2015-01-01

    Summary Manipulation of protein kinase activity is widely used to dissect signaling pathways controlling physiological and pathological processes. Common methods often cannot provide the desired spatial and temporal resolution in control of kinase activity. Regulation of kinase activity by photocaged kinase inhibitors has been successfully used to achieve tight temporal and local control, but inhibitors are limited to inactivation of kinases, and often do not provide the desired specificity. Here we report detailed methods for light-mediated activation of kinases in living cells using engineered rapamycin-regulated kinases (RapR-kinases) in conjunction with a photocaged analog of rapamycin. PMID:24718793

  9. Accelerating wavefunction in density-functional-theory embedding by truncating the active basis set.

    PubMed

    Bennie, Simon J; Stella, Martina; Miller, Thomas F; Manby, Frederick R

    2015-07-14

    Methods where an accurate wavefunction is embedded in a density-functional description of the surrounding environment have recently been simplified through the use of a projection operator to ensure orthogonality of orbital subspaces. Projector embedding already offers significant performance gains over conventional post-Hartree-Fock methods by reducing the number of correlated occupied orbitals. However, in our first applications of the method, we used the atomic-orbital basis for the full system, even for the correlated wavefunction calculation in a small, active subsystem. Here, we further develop our method for truncating the atomic-orbital basis to include only functions within or close to the active subsystem. The number of atomic orbitals in a calculation on a fixed active subsystem becomes asymptotically independent of the size of the environment, producing the required O(N(0)) scaling of cost of the calculation in the active subsystem, and accuracy is controlled by a single parameter. The applicability of this approach is demonstrated for the embedded many-body expansion of binding energies of water hexamers and calculation of reaction barriers of SN2 substitution of fluorine by chlorine in α-fluoroalkanes.

  10. Does a physically active lifestyle attenuate decline in all cognitive functions in old age?

    PubMed

    Ballesteros, Soledad; Mayas, Julia; Reales, Jose Manuel

    2013-07-01

    In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

  11. Modeling function-perfusion behavior in liver lobules including tissue, blood, glucose, lactate and glycogen by use of a coupled two-scale PDE-ODE approach.

    PubMed

    Ricken, T; Werner, D; Holzhütter, H G; König, M; Dahmen, U; Dirsch, O

    2015-06-01

    This study focuses on a two-scale, continuum multicomponent model for the description of blood perfusion and cell metabolism in the liver. The model accounts for a spatial and time depending hydro-diffusion-advection-reaction description. We consider a solid-phase (tissue) containing glycogen and a fluid-phase (blood) containing glucose as well as lactate. The five-component model is enhanced by a two-scale approach including a macroscale (sinusoidal level) and a microscale (cell level). The perfusion on the macroscale within the lobules is described by a homogenized multiphasic approach based on the theory of porous media (mixture theory combined with the concept of volume fraction). On macro level, we recall the basic mixture model, the governing equations as well as the constitutive framework including the solid (tissue) stress, blood pressure and solutes chemical potential. In view of the transport phenomena, we discuss the blood flow including transverse isotropic permeability, as well as the transport of solute concentrations including diffusion and advection. The continuum multicomponent model on the macroscale finally leads to a coupled system of partial differential equations (PDE). In contrast, the hepatic metabolism on the microscale (cell level) was modeled via a coupled system of ordinary differential equations (ODE). Again, we recall the constitutive relations for cell metabolism level. A finite element implementation of this framework is used to provide an illustrative example, describing the spatial and time-depending perfusion-metabolism processes in liver lobules that integrates perfusion and metabolism of the liver.

  12. Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database

    PubMed Central

    2012-01-01

    Background Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD) and Becker (BMD) muscular dystrophies. The most common DMD mutations are frameshift mutations resulting in an absence of dystrophin from tissues. In-frame DMD mutations are less frequent and result in a protein with partial wild-type dystrophin function. The aim of this study was to highlight structural and functional modifications of dystrophin caused by in-frame mutations. Methods and results We developed a dedicated database for dystrophin, the eDystrophin database. It contains 209 different non frame-shifting mutations found in 945 patients from a French cohort and previous studies. Bioinformatics tools provide models of the three-dimensional structure of the protein at deletion sites, making it possible to determine whether the mutated protein retains the typical filamentous structure of dystrophin. An analysis of the structure of mutated dystrophin molecules showed that hybrid repeats were reconstituted at the deletion site in some cases. These hybrid repeats harbored the typical triple coiled-coil structure of native repeats, which may be correlated with better function in muscle cells. Conclusion This new database focuses on the dystrophin protein and its modification due to in-frame deletions in BMD patients. The observation of hybrid repeat reconstitution in some cases provides insight into phenotype-genotype correlations in dystrophin diseases and possible strategies for gene therapy. The eDystrophin database is freely available: http://edystrophin.genouest.org/. PMID:22776072

  13. Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives.

    PubMed

    Dea-Ayuela, M Auxiliadora; Bilbao-Ramos, Pablo; Bolás-Fernández, Francisco; González-Cardenete, Miguel A

    2016-10-01

    Abietane-type diterpenoids, either naturally occurring or synthetic, have shown a wide range of pharmacological actions, including antiprotozoal properties. In this study, we report on the antileishmanial evaluation of a series of (+)-dehydroabietylamine derivatives functionalized at C7 and/or C12. Thus, the activity in vitro against Leishmania infantum, Leishmania donovani, Leishmania amazonensis and Leishmania guyanensis, was studied. Most of the benzamide derivatives showed activities at low micromolar concentration against cultured promastigotes of Leishmania spp. (IC50 = 2.2-46.8 μM), without cytotoxicity on J774 macrophage cells. Compound 15, an acetamide, was found to be the most active leishmanicidal agent, though it presented some cytotoxicity on J774 cells. Among the benzamide derivatives, compounds 8 and 10, were also active against L. infantum intracellular amastigotes, being 18- and 23-fold more potent than the reference compound miltefosine, respectively. Some structure-activity relationships have been identified for the antileishmanial activity in these dehydroabietylamine derivatives. PMID:27318121

  14. Longitudinal relationships of executive cognitive function and parent influence to child substance use and physical activity.

    PubMed

    Pentz, Mary Ann; Riggs, Nathaniel R

    2013-06-01

    Considered a set of neuro-cognitive skills, executive cognitive function (ECF) may serve to protect children from initiating substance use, although its role relative to other protective influences that parents and physical activity might provide is not known. As part of a large multiple health risk behavior trial for prevention of substance use and obesity, Pathways, the present study evaluated the relative impact of ECF on lifetime substance use (tobacco and alcohol) and physical activity in a panel of fourth grade children over a 6-month period (N = 1005; 51 % female; 25 % on free/reduced lunch; 60 % Hispanic/Latino or multi-racial; 28 elementary schools). A self-report survey included measures of ECF, lifetime tobacco and alcohol use, out-of-school physical activity, exercising with parents, and parent rules about food/sedentary behavior, monitoring, and arguing, was adapted for use with children. A path analysis demonstrated that ECF was the major predictor of lower substance use and higher physical activity and exercising with parents. Physical activity and exercising with parents showed reciprocal positive relationships. Findings suggest that promoting ECF skills should be a major focus of child health promotion and substance use prevention programs, although the potential protective effects of physical activity and exercise with parents on substance use in this young age group are not yet clear. PMID:23345012

  15. Anterior cruciate ligament injury after more than 20 years: I. Physical activity level and knee function.

    PubMed

    Tengman, E; Brax Olofsson, L; Nilsson, K G; Tegner, Y; Lundgren, L; Häger, C K

    2014-12-01

    Little is known about physical activity level and knee function including jump capacity and fear of movement/reinjury more than 20 years after injury of the anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury participated (23 ± 2 years post-injury): 33 treated with physiotherapy in combination with surgical reconstruction (ACLR ), and 37 treated with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls. Assessment included knee-specific and general physical activity level [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)], knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner scores than controls (P < 0.001), while IPAQ score was similar. ACL-injured demonstrated inferior jump capacity in injured compared with noninjured leg (6-25%, P < 0.001-P = 0.010 in the different jumps), while noninjured leg had equal jump capacity as controls. ACL groups scored 33 ± 7 and 32 ± 7 of 68 on TSK. Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to-high OA than for no-or-low OA, while there were no differences for physical activity and jump capacity. Regardless of treatment, there are still negative knee-related effects of ACL injury more than 20 years later.

  16. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  17. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  18. 24 CFR 4100.1 - Functions and activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and amenities, and improve the neighborhood's image and the functioning of its real estate market are... bodies providing financing. (B) The Owner Rehab Housing program assists low to moderate income...

  19. Performance of Density Functionals for Activation Energies of Zr-Mediated Reactions.

    PubMed

    Sun, Yuanyuan; Chen, Hui

    2013-11-12

    Coupled cluster CCSD(T) calculations with core-valence correlation and complete basis set (CBS) limit extrapolation are used to benchmark the performance of commonly used density functionals in computing energy barriers for Zr-mediated reactions involving zirconocene species. These reactions include (a) insertions of the Zr-H bond of Cp2Zr(H)Cl into C═C, C≡C, and C═O bonds and (b) C-H activations by Zr═N bond in Cp2Zr═NH. The best performing functionals are M06-L, M06, and M06-2X in the M06 series, all having mean unsigned deviations (MUD) less than 2 kcal/mol. The worst performing functional is OLYP, with a distinctly large MUD of more than 10 kcal/mol. Considering also the trends in barrier heights and the systematic barrier height deviation, our best recommended functional is M06-2X. In this work, DFT empirical dispersion correction (DFT-D3) is found to improve the performance of barrier height values for most functionals (especially of OLYP and B3LYP). With DFT empirical dispersion correction, we also recommend M06-2X for reaction barrier calculations of Zr-mediated reactions.

  20. Partial Enteral Nutrition Preserves Elements of Gut Barrier Function, Including Innate Immunity, Intestinal Alkaline Phosphatase (IAP) Level, and Intestinal Microbiota in Mice.

    PubMed

    Wan, Xiao; Bi, Jingcheng; Gao, Xuejin; Tian, Feng; Wang, Xinying; Li, Ning; Li, Jieshou

    2015-08-01

    Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.

  1. Partial Enteral Nutrition Preserves Elements of Gut Barrier Function, Including Innate Immunity, Intestinal Alkaline Phosphatase (IAP) Level, and Intestinal Microbiota in Mice

    PubMed Central

    Wan, Xiao; Bi, Jingcheng; Gao, Xuejin; Tian, Feng; Wang, Xinying; Li, Ning; Li, Jieshou

    2015-01-01

    Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota. PMID:26247961

  2. Versatile, Reversible, and Reusable Gel of a Monocholesteryl Conjugated Calix[4]arene as Functional Material to Store and Release Dyes and Drugs Including Doxorubicin, Curcumin, and Tocopherol.

    PubMed

    Bandela, Anil Kumar; Hinge, Vijaya Kumar; Yarramala, Deepthi S; Rao, Chebrolu Pulla

    2015-06-01

    Gels are interesting soft materials owing to their functional properties leading to potential applications. This paper deals with the synthesis of monocholesteryl derivatized calix[4]arene (G) and its instantaneous gelation at a minimum gelator concentration of 0.6% in 1:1 v/v THF/acetonitrile. The gel shows remarkable thermoreversibility by exhibiting Tgel→sol at ∼48 °C and is demonstrated for several cycles. The gel shows an organized network of nanobundles, while that of the sol shows spherical nanoaggregates in microscopy. A bundle with ∼12 nm diameter possessing hydrophobic pockets in itself is obtained from computationally modeled gel, and hence the gel is suitable for storage and release applications. The guest-entrapped gels exhibit the same microstructures as that observed with simple gels, while fluorescence spectra and molecular mechanics suggests that the drug molecules occupy the hydrophobic pockets. All the entrapped drug molecules are released into water, suggesting a complete recovery of the trapped species. The reusability of the gel for the storage and release of the drug into water is demonstrated for four consecutive cycles, and hence the gel formed from G acts as a functional material that finds application in drug delivery.

  3. Physical Activity as a Function of Women's Health.

    PubMed

    Đukanović, Nina; Mašić, Zoran; Kostovski, Žarko; Širić, Vesna; Blažević, Stipe

    2015-07-01

    Physical activity means any form of body movement that is associated with certain metabolic demands. At the same time, physical activity is one of the most important steps in the maintenance, protection and improvement of health. There is strong evidence to suggest that higher levels of physical activity are associated with numerous preventive effects and therapeutic effects in the treatment of many diseases. Although they account for a larger portion of the population, physical inactivity is more often registered in women, which can be attributed to a variety of reasons--ranging from anatomical and physiological to the socio-psychological. The present paper discusses some of the most important benefits associated with physical activity in women, to encourage their greater participation in various forms of physical activity.

  4. Heterogeneity in Pseudomonas aeruginosa Biofilms Includes Expression of Ribosome Hibernation Factors in the Antibiotic-Tolerant Subpopulation and Hypoxia-Induced Stress Response in the Metabolically Active Population

    PubMed Central

    Williamson, Kerry S.; Richards, Lee A.; Perez-Osorio, Ailyn C.; Pitts, Betsey; McInnerney, Kathleen; Stewart, Philip S.

    2012-01-01

    Bacteria growing in biofilms are physiologically heterogeneous, due in part to their adaptation to local environmental conditions. Here, we characterized the local transcriptome responses of Pseudomonas aeruginosa growing in biofilms by using a microarray analysis of isolated biofilm subpopulations. The results demonstrated that cells at the top of the biofilms had high mRNA abundances for genes involved in general metabolic functions, while mRNA levels for these housekeeping genes were low in cells at the bottom of the biofilms. Selective green fluorescent protein (GFP) labeling showed that cells at the top of the biofilm were actively dividing. However, the dividing cells had high mRNA levels for genes regulated by the hypoxia-induced regulator Anr. Slow-growing cells deep in the biofilms had little expression of Anr-regulated genes and may have experienced long-term anoxia. Transcripts for ribosomal proteins were associated primarily with the metabolically active cell fraction, while ribosomal RNAs were abundant throughout the biofilms, indicating that ribosomes are stably maintained even in slowly growing cells. Consistent with these results was the identification of mRNAs for ribosome hibernation factors (the rmf and PA4463 genes) at the bottom of the biofilms. The dormant biofilm cells of a P. aeruginosa Δrmf strain had decreased membrane integrity, as shown by propidium iodide staining. Using selective GFP labeling and cell sorting, we show that the dividing cells are more susceptible to killing by tobramycin and ciprofloxacin. The results demonstrate that in thick P. aeruginosa biofilms, cells are physiologically distinct spatially, with cells deep in the biofilm in a viable but antibiotic-tolerant slow-growth state. PMID:22343293

  5. Design of spin-forbidden transitions for polypyridyl metal complexes by time-dependent density functional theory including spin-orbit interaction.

    PubMed

    Kanno, Shohei; Imamura, Yutaka; Hada, Masahiko

    2016-05-25

    We explore spin-forbidden transitions for a Ru dye with an N3 skeleton and an Fe dye with a DX1 skeleton by time-dependent density functional theory with spin-orbit interaction. The modified N3-based Ru dye with iodine anions has an absorption edge in the long wavelength region which is not observed in the original N3 dye. The long wavelength absorption edge originates from the spin-orbit interaction with iodine. Although the Fe dye has a small spin-orbit interaction, because of less spin-orbit interaction from the light metal, spin-forbidden transitions also occur for DX1-based Fe dye systems with iodine anions. This result indicates that the introduction of iodine can strengthen the spin-orbit interaction for a dye sensitizer and offers a new approach for designing spin-forbidden transitions.

  6. The mRNA decay factor PAT1 functions in a pathway including MAP kinase 4 and immune receptor SUMM2

    PubMed Central

    Roux, Milena Edna; Rasmussen, Magnus Wohlfahrt; Palma, Kristoffer; Lolle, Signe; Regué, Àngels Mateu; Bethke, Gerit; Glazebrook, Jane; Zhang, Weiping; Sieburth, Leslie; Larsen, Martin R; Mundy, John; Petersen, Morten

    2015-01-01

    Multi-layered defense responses are activated in plants upon recognition of invading pathogens. Transmembrane receptors recognize conserved pathogen-associated molecular patterns (PAMPs) and activate MAP kinase cascades, which regulate changes in gene expression to produce appropriate immune responses. For example, Arabidopsis MAP kinase 4 (MPK4) regulates the expression of a subset of defense genes via at least one WRKY transcription factor. We report here that MPK4 is found in complexes in vivo with PAT1, a component of the mRNA decapping machinery. PAT1 is also phosphorylated by MPK4 and, upon flagellin PAMP treatment, PAT1 accumulates and localizes to cytoplasmic processing (P) bodies which are sites for mRNA decay. Pat1 mutants exhibit dwarfism and de-repressed immunity dependent on the immune receptor SUMM2. Since mRNA decapping is a critical step in mRNA turnover, linking MPK4 to mRNA decay via PAT1 provides another mechanism by which MPK4 may rapidly instigate immune responses. PMID:25603932

  7. The electronic spectrum of AgCl2: Ab initio benchmark versus density-functional theory calculations on the lowest ligand-field states including spin-orbit effects

    NASA Astrophysics Data System (ADS)

    Ramírez-Solís, A.; Poteau, R.; Daudey, J. P.

    2006-01-01

    The XΠg2, Σg+2, and Δg2 states of AgCl2 have been studied through benchmark ab initio complete active space self-consistent field plus second-order complete active space multireference Möller-Plesset algorithm (CASSCF +CASPT2) and complete active space self-consistent field plus averaged coupled pair functional (CASSCF +ACPF) and density-functional theory (DFT) calculations using especially developed basis sets to study the transition energies, geometries, vibrational frequencies, Mulliken charges, and spin densities. The spin-orbit (SO) effects were included through the effective Hamiltonian formalism using the ΛSΣ ACPF energies as diagonal elements. At the ACPF level, the ground state is Πg2 in contradiction with ligand-field theory, SCF, and large CASSCF; the adiabatic excitation energies for the Σg+2 and Δg2 states are 1640 and 18230cm-1, respectively. The inclusion of the SO effects leads to a pure Ω =3/2(Πg2) ground state, a Ω =1/2 (66%Πg2 and 34%Σg+2) A state, a Ω =1/2 (34%Πg2 and 66%Σg+2) B state, a Ω =5/2(Δg2)C state, and a Ω =3/2(99%Δg2)D state. The X-A, X-B, X-C, and X-D transition energies are 485, 3715, 17 246, and 20110cm-1, respectively. The B97-2, B3LYP, and PBE0 functionals overestimate by ≈100% the XΠg2-Σg+2Te but provide a qualitative energetic ordering in good agreement with ACPF results. B3LYP with variable exchange leads to a 42% optimal Hartree-Fock exchange for transition energies but all equilibrium geometries get worsened. Asymptotic corrections to B3LYP do not provide improved values. The nature of the bonding in the XΠg2 state is very different from that of CuCl2 since the Mulliken charge on the metal is 1.1 while the spin density is only 0.35. DFT strongly delocalizes the spin density providing even smaller values of around 0.18 on Ag not only for the ground state, but also for the Σg+2 state.

  8. Fetal Functional Brain Age Assessed from Universal Developmental Indices Obtained from Neuro-Vegetative Activity Patterns

    PubMed Central

    Hoyer, Dirk; Tetschke, Florian; Jaekel, Susan; Nowack, Samuel; Witte, Otto W.; Schleußner, Ekkehard; Schneider, Uwe

    2013-01-01

    Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4–40.3 weeks of gestation) preclassified in quiet sleep (n = 113, 63 females) and active sleep (n = 286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R2 of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent f

  9. [Functional cerebral activity in a state of rest: connectivity networks].

    PubMed

    Proal, Erika; Alvarez-Segura, Mar; de la Iglesia-Vayá, María; Martí-Bonmatí, Luis; Castellanos, F Xavier

    2011-03-01

    Functional connectivity can be measured during task-based functional magnetic resonance imaging (fMRI), or in the absence of specific stimuli or tasks. In either case, the study of low frequency fluctuations in the BOLD signal reveals patterns of synchronization which delineate the intrinsic functional architecture of the brain. The scientific community now has available shared resources to accelerate the exploitation of resting state fMRI with the objectives of improving diagnostic methods and leading to better treatments grounded in neuroscience. Fomenting a collaborative scientific culture will accelerate our understanding of the underlying phenonmemna. Recently, the Spanish Resting State Network (SRSN) has joined this collaborative effort by creating a setting to facilitate collaboration among the various neuroscience research groups working in Spanish (http://www.nitrc.org/projects/srsn). PMID:21365601

  10. Methodology for the systems engineering process. Volume 1: System functional activities

    NASA Technical Reports Server (NTRS)

    Nelson, J. H.

    1972-01-01

    Systems engineering is examined in terms of functional activities that are performed in the conduct of a system definition/design, and system development is described in a parametric analysis that combines functions, performance, and design variables. Emphasis is placed on identification of activities performed by design organizations, design specialty groups, as well as a central systems engineering organizational element. Identification of specific roles and responsibilities for doing functions, and monitoring and controlling activities within the system development operation are also emphasized.

  11. 25 CFR 170.622 - What IRR programs, functions, services, and activities are subject to the self-governance...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the agreement, are subject to the regulations in 25 CFR 1000 subpart K, including applicable... are subject to the self-governance construction regulations? 170.622 Section 170.622 Indians BUREAU OF..., functions, services, and activities are subject to the self-governance construction regulations? All...

  12. 25 CFR 170.622 - What IRR programs, functions, services, and activities are subject to the self-governance...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the agreement, are subject to the regulations in 25 CFR 1000 subpart K, including applicable... are subject to the self-governance construction regulations? 170.622 Section 170.622 Indians BUREAU OF..., functions, services, and activities are subject to the self-governance construction regulations? All...

  13. 25 CFR 170.622 - What IRR programs, functions, services, and activities are subject to the self-governance...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the agreement, are subject to the regulations in 25 CFR 1000 subpart K, including applicable... are subject to the self-governance construction regulations? 170.622 Section 170.622 Indians BUREAU OF..., functions, services, and activities are subject to the self-governance construction regulations? All...

  14. 25 CFR 170.622 - What IRR programs, functions, services, and activities are subject to the self-governance...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the agreement, are subject to the regulations in 25 CFR 1000 subpart K, including applicable... are subject to the self-governance construction regulations? 170.622 Section 170.622 Indians BUREAU OF..., functions, services, and activities are subject to the self-governance construction regulations? All...

  15. Autoantibodies to the functionally active RING-domain of Ro52/SSA are associated with disease activity in patients with lupus.

    PubMed

    Kvarnström, M; Dzikaite-Ottosson, V; Ottosson, L; Gustafsson, J T; Gunnarsson, I; Svenungsson, E; Wahren-Herlenius, M

    2013-04-01

    The Ro52 protein of the Ro/SSA antigen was recently defined as an E3 ligase controlling cytokine production. Autoantibodies from systemic lupus erythematosus (SLE) patients targeting the Ro52-RING domain, containing the E3 ligase activity, have been shown to inhibit the E3 ligase activity of Ro52. The objective of the present study was to investigate correlations between clinical parameters in patients with SLE and levels of Ro/SSA (Ro52 and Ro60) and La/SSB autoantibodies, including autoantibodies directed towards the functional RING and B-box domains of the Ro52 protein. SLE patients (n=232) were clinically examined and disease activity indices collected concurrently to blood sampling. The samples were analyzed for immunological parameters including autoantibodies. Ro52 autoantibody levels were associated with more variables than the other analyzed antibodies and were significantly associated with several individual items related to sSS and the diagnosis of sSS itself (p=0.004). Other associated variables were high sedimentation rate (p=0.0003), levels of immunoglobulins (p=0.0003), and an inverse correlation with levels of lymphocytes (p=0.003) and leukocytes (p=0.01). Antibodies to the RING domain of Ro52, which is the functionally active domain with E3 ligase activity, were significantly correlated with disease activity as measured by the SLAM score. We conclude that autoantibodies against Ro52 and in particular its functional RING domain are important in lupus patients and associated with several clinical and laboratory features of the disease. The impact on disease activity of Ro52-RING specific antibodies was especially noted, and could imply a functional role for these autoantibodies in inhibiting Ro52 activity, which is important for the control of proinflammatory cytokine production, including type 1 interferons.

  16. U.S. Geological Survey Scientific Activities in the Exploration of Antarctica: Introduction to Antarctica (Including USGS Field Personnel: 1946-59)

    USGS Publications Warehouse

    Tony K. Meunier Edited by Williams, Richard S.; Ferrigno, Jane G.

    2007-01-01

    international) programs in biology, geology, geophysics, hydrology, and mapping. Therefore, the USGS was the obvious choice for these tasks, because it already had a professional staff of experienced mapmakers, scientists, and program managers with the foresight, dedication, and understanding of the need for accurate maps to support the science programs in Antarctica when asked to do so by the U.S. National Academy of Sciences. Public Laws 85-743 and 87-626, signed in August 1958, and in September 1962, respectively, authorized the Secretary, U.S. Department of the Interior, through the USGS, to support mapping and scientific work in Antarctica (Meunier, 1979 [2007], appendix A). Open-File Report 2006-1116 includes scanned facsimiles of postal cachets. It has become an international practice to create postal cachets to commemorate special events and projects in Antarctica. A cachet is defined as a seal or commemorative design printed or stamped on an envelope to mark a philatelic or special event. The inked impression illustrates to the scientist, historian, stamp collector, and general public the multidisciplinary science projects staffed by USGS and collaborating scientists during the field season. Since 1960, philatelic cachets have been created by team members for each USGS field season and, in most cases, these cachets depict the specific geographic areas and field season program objectives. The cachets become a convenient documentation of the people, projects, and geographic places of interest for that year. Because the cachets are representative of USGS activities, each year's cachet is included as a digital facsimile in that year's Open-File Report. In the 1980s, multiple USGS cachets were prepared each year, one for use by the winter team at Amundsen-Scott South Pole Station and the other for the project work areas of the austral summer field season programs.

  17. Mitochondrial function provides instructive signals for activation-induced B-cell fates.

    PubMed

    Jang, Kyoung-Jin; Mano, Hiroto; Aoki, Koji; Hayashi, Tatsunari; Muto, Akihiko; Nambu, Yukiko; Takahashi, Katsu; Itoh, Katsuhiko; Taketani, Shigeru; Nutt, Stephen L; Igarashi, Kazuhiko; Shimizu, Akira; Sugai, Manabu

    2015-04-10

    During immune reactions, functionally distinct B-cell subsets are generated by stochastic processes, including class-switch recombination (CSR) and plasma cell differentiation (PCD). In this study, we show a strong association between individual B-cell fates and mitochondrial functions. CSR occurs specifically in activated B cells with increased mitochondrial mass and membrane potential, which augment mitochondrial reactive oxygen species (mROS), whereas PCD occurs in cells with decreased mitochondrial mass and potential. These events are consequences of initial slight changes in mROS in mitochondria(high) B-cell populations. In CSR-committed cells, mROS attenuates haeme synthesis by inhibiting ferrous ion addition to protoporphyrin IX, thereby maintaining Bach2 function. Reduced mROS then promotes PCD by increasing haeme synthesis. In PCD-committed cells, Blimp1 reduces mitochondrial mass, thereby reducing mROS levels. Identifying mROS as a haeme synthesis regulator increases the understanding of mechanisms regulating haeme homeostasis and cell fate determination after B-cell activation.

  18. Tumor Suppressive Function of p21-activated Kinase 6 in Hepatocellular Carcinoma.

    PubMed

    Liu, Weisi; Liu, Yidong; Liu, Haiou; Zhang, Weijuan; Fu, Qiang; Xu, Jiejie; Gu, Jianxin

    2015-11-20

    Our previous studies identified the oncogenic role of p21-activated kinase 1 (PAK1) in hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Contrarily, PAK6 was found to predict a favorable prognosis in RCC patients. Nevertheless, the ambiguous tumor suppressive function of PAK6 in hepatocarcinogenesis remains obscure. Herein, decreased PAK6 expression was found to be associated with tumor node metastasis stage progression and unfavorable overall survival in HCC patients. Additionally, overexpression and silence of PAK6 experiments showed that PAK6 inhibited xenografted tumor growth in vivo, and restricted cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis and anoikis in vitro. Moreover, overexpression of kinase dead and nuclear localization signal deletion mutants of PAK6 experiments indicated the tumor suppressive function of PAK6 was partially dependent on its kinase activity and nuclear translocation. Furthermore, gain or loss of function in polycomb repressive complex 2 (PRC2) components, including EZH2, SUZ12, and EED, elucidated epigenetic control of H3K27me3-arbitrated PAK6 down-regulation in hepatoma cells. More importantly, negative correlation between PAK6 and EZH2 expression was observed in hepatoma tissues from HCC patients. These data identified the tumor suppressive role and potential underlying mechanism of PAK6 in hepatocarcinogenesis.

  19. Antibody Fc functional activity of intravenous immunoglobulin preparations treated with solvent-detergent for virus inactivation.

    PubMed

    Yang, Y H; Ngo, C; Yeh, I N; Uemura, Y

    1994-01-01

    We report here results of in vitro comparisons of the Fc functional activity of a second-generation intravenous immunoglobulin (IGIV) preparation (Venoglobulin-I) and a third-generation IGIV product that includes a deliberate virus-inactivation step (Venoglobulin-S). Both formulations showed equivalent Fc-mediated function against viral antigens (rubella, influenza A, and influenza B) by single-radial hemolysis test, and against group B Streptococcus, Staphylococcus aureus and Escherichia coli by opsonophagocytosis assay. In addition, we showed by three different immunochemical reactions and by HPLC analysis that both preparations consisted of mostly monomeric IgG and contained very low levels of complement-fixing IgG aggregates. However, IgG aggregation induced by heating at 63 degrees C markedly enhanced fixation of Clq and C3 and binding to Raji cells, indicating that the IgG molecules retained their complement-fixing capacity. Thus, the incorporation of a virus inactivation step in the manufacture of our third-generation IGIV did not alter the Fc functional activities of the IgG, as measured by these in vitro assay systems.

  20. In vitro activity of ceftazidime/avibactam against Gram-negative pathogens isolated from pneumonia in hospitalised patients, including ventilated patients.

    PubMed

    Flamm, Robert K; Nichols, Wright W; Sader, Helio S; Farrell, David J; Jones, Ronald N

    2016-03-01

    The activities of the novel β-lactam/non-β-lactam β-lactamase inhibitor combination ceftazidime/avibactam and comparators were evaluated against isolates from pneumonia in hospitalised patients including ventilated patients (PHP, pneumonia not designated as VABP; VABP, pneumonia in ventilated patients). Isolates were from the European-Mediterranean region (EuM), China and the USA collected in the SENTRY Antimicrobial Surveillance Program between 2009 and 2011 inclusive. A total of 2393 organisms from PHP were from the EuM, 888 from China and 3213 from the USA; from VABP patients there were 918, 97 and 692 organisms collected, respectively. Among Enterobacteriaceae from PHP, ceftazidime/avibactam MIC90 values against Escherichia coli ranged from 0.25-0.5mg/L and Klebsiella spp. MIC90 values were 0.5mg/L in each region. Among VABP isolates, MIC90 values for ceftazidime/avibactam against E. coli were 0.25mg/L; for Klebsiella spp. from VABP patients, MIC90 values were similar to those obtained against PHP isolates. The MIC of ceftazidime/avibactam was ≤8mg/L against 92-96% of Pseudomonas aeruginosa isolated from PHP patients. Isolates of P. aeruginosa from VABP patients were of lower susceptibility to all antibacterial agents (e.g. depending on region, meropenem susceptibilities were 51.2-69.4% in contrast to 68.3-76.7% among PHP patients). However, ceftazidime/avibactam inhibited 79.2-95.4% of VABP isolates at an MIC of ≤8mg/L. Acinetobacter spp. were resistant to many agents and only rates of susceptibility to colistin were >90% across all regions both for PHP and VABP isolates. Ceftazidime/avibactam was generally active against a high proportion of isolates resistant to ceftazidime from PHP and VAPB patients.

  1. Spectroscopic and computational investigations on the origin of charge transfer between included neutral guest molecules and a functionalized anionic layered host.

    PubMed

    Dutta, Dipak; Tummanapelli, Anil Kumar

    2016-08-10

    Layered double hydroxides (LDHs) or anionic clays are an important class of ion-exchange materials, well known for drug and gene delivery and several other applications including catalysis, bioactive nanocomposite, electroactive and photoactive materials. Their structure is based on positively charged brucite-like inorganic sheets with the interlamellar space being occupied by charge-compensating exchangeable anions. In spite of having a vast scope many of the applications of LDHs are restricted as their host-guest chemistry is limited to ion-exchange reactions. Recently we have shown for the first time that charge-transfer interactions can be used as a driving force for the insertion of neutral guest molecules (ortho- and para-chloranil) within the galleries of an Mg-Al LDH by forming a charge-transfer complex with aniline pre-intercalated as p-aminobenzoate anion. Here, we have performed quantum chemical calculations in combination with molecular dynamics simulations to elucidate the nature of interactions, arrangement and the evaluation of electronic and Raman spectral signatures of the chloranil charge-transfer complex included within the galleries of the Mg-Al LDH. The natural bond orbital (NBO) analysis has been used to understand the nature and origin of the unidirectional charge-transfer that lead to the unusual insertion of chloranil in the galleries of the Mg-Al LDH. The NBO analysis reveals that a considerable amount of electronic charge redistribution occurs from the p-aminobenzoate to the chloranil during latter's insertion within the LDH galleries with a very negligible amount of back donation. This work is expected to pave the way for understanding the host-guest chemistry and targeted and controlled delivery of poorly soluble drugs. PMID:27461409

  2. Catalytic activities of platinum nanotubes: a density functional study

    NASA Astrophysics Data System (ADS)

    Mukherjee, Prajna; Gupta, Bikash C.; Jena, Puru

    2015-10-01

    In this work we investigate the catalytic properties of platinum nanotubes using density functional theory based calculations. In particular, we study the dissociation of hydrogen and oxygen molecules as well as oxidation of CO molecules. The results indicate that platinum nanotubes have good catalytic properties and can be effectively used in converting CO molecule to CO2.

  3. Towards computational prediction of microRNA function and activity

    PubMed Central

    Ulitsky, Igor; Laurent, Louise C.; Shamir, Ron

    2010-01-01

    While it has been established that microRNAs (miRNAs) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual miRNAs are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human miRNAs. Our approach improves upon standard statistical tools by addressing specific characteristics of miRNA regulation. Our analysis is based on a novel compendium of experimentally verified miRNA-pathway and miRNA-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel miRNA-regulated pathways, refines the annotation of miRNAs for which only crude functions are known, and assigns differential functions to miRNAs with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify miRNAs and genomic miRNA clusters with functional importance in specific stages of early human development. A full list of the predicted mRNA functions is available at http://acgt.cs.tau.ac.il/fame/. PMID:20576699

  4. Antifouling activity of enzyme‐functionalized silica nanobeads

    PubMed Central

    Zanoni, Michele; Habimana, Olivier; Amadio, Jessica

    2015-01-01

    ABSTRACT The amelioration of biofouling in industrial processing equipment is critical for performance and reliability. While conventional biocides are effective in biofouling control, they are potentially hazardous to the environment and in some cases corrosive to materials. Enzymatic approaches have been shown to be effective and can overcome the disadvantages of traditional biocides, however they are typically uneconomic for routine biofouling control. The aim of this study was to design a robust and reusable enzyme‐functionalized nano‐bead system having biofilm dispersion properties. This work describes the biochemical covalent functionalization of silica‐based nanobeads (hereafter referred to as Si‐NanoB) with Proteinase K (PK). Results showed that PK‐functionalized Si‐NanoB are effective in dispersing both protein‐based model biofilms and structurally altering Pseudomonas fluorescens biofilms, with significant decreases in surface coverage and thickness of 30.1% and 38.85%, respectively, while increasing surface roughness by 19 % following 24 h treatments on bacterial biofilms. This study shows that enzyme‐functionalized nanobeads may potentially be an environmentally friendly and cost effective alternative to pure enzyme and chemical treatments. Biotechnol. Bioeng. 2016;113: 501–512. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:26370186

  5. Antibiotic production by soil bacteria: diversity, activity and natural functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The living components of soils, the micro- and macrobiota, play an essential role in several life support functions as they enable soils to recycle nutrients, inactive contaminants, suppress plant pathogens and serve as a suitable substrate for plant growth. Beneficial bacteria occur naturally in s...

  6. fNIRS: An Emergent Method to Document Functional Cortical Activity during Infant Movements

    PubMed Central

    Nishiyori, Ryota

    2016-01-01

    The neural basis underlying the emergence of goal-directed actions in infants has been severely understudied, with minimal empirical evidence for hypotheses proposed. This was largely due to the technological constraints of traditional neuroimaging techniques. Recently, functional near-infrared spectroscopy (fNIRS) technology has emerged as a tool developmental scientists are finding useful to examine cortical activity, particularly in young children and infants due to its greater tolerance to movements than other neuroimaging techniques. fNIRS provides an opportunity to finally begin to examine the neural underpinnings as infants develop goal-directed actions. In this methodological paper, I will outline the utility, challenges, and outcomes of using fNIRS to measure the changes in cortical activity as infants reach for an object. I will describe the advantages and limitations of the technology, the setup I used to study primary motor cortex activity during infant reaching, and example steps in the analyses processes. I will present exemplar data to illustrate the feasibility of this technique to quantify changes in hemodynamic activity as infants move. The viability of this research method opens the door to expanding studies of the development of neural activity related to goal-directed actions in infants. I encourage others to share details of techniques used, as well, including analyticals, to help this neuroimaging technology grow as others, such as EEG and fMRI have. PMID:27148141

  7. Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation.

    PubMed Central

    Teboul, L; Febbraio, M; Gaillard, D; Amri, E Z; Silverstein, R; Grimaldi, P A

    2001-01-01

    Fatty acid translocase (FAT/CD36) is a cell-surface glycoprotein that functions as a receptor/transporter for long-chain fatty acids (LCFAs), and interacts with other protein and lipid ligands. FAT/CD36 is expressed by various cell types, including platelets, monocytes/macrophages and endothelial cells, and tissues with an active LCFA metabolism, such as adipose, small intestine and heart. FAT/CD36 expression is induced during adipose cell differentiation and is transcriptionally up-regulated by LCFAs and thiazolidinediones in pre-adipocytes via a peroxisome-proliferator-activated receptor (PPAR)-mediated process. We isolated and analysed the murine FAT/CD36 promoter employing C(2)C(12)N cells directed to differentiate to either adipose or muscle. Transient transfection studies revealed that the 309 bp upstream from the start of exon 1 confer adipose specific activity. Sequence analysis of this DNA fragment revealed the presence of two imperfect direct repeat-1 elements. Electrophoretic mobility-shift assay demonstrated that these elements were peroxisome-proliferator-responsive elements (PPREs). Mutagenesis and transfection experiments indicated that both PPREs co-operate to drive strong promoter activity in adipose cells. We conclude that murine FAT/CD36 expression in adipose tissue is dependent upon transcriptional activation via PPARs through binding to two PPREs located at -245 to -233 bp and -120 to -108 bp from the transcription start site. PMID:11716758

  8. Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI

    PubMed Central

    Bilevicius, Elena; Kolesar, Tiffany A.; Kornelsen, Jennifer

    2016-01-01

    Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. PMID:27104572

  9. Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex.

    PubMed

    Marins, Theo F; Rodrigues, Erika C; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

    2015-01-01

    Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

  10. Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

    PubMed Central

    Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

    2015-01-01

    Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

  11. Physical Activity is Associated with Better Neurocognitive and Everyday Functioning Among Older Adults with HIV Disease

    PubMed Central

    Fazeli, Pariya L.; Marquine, Maria J.; Dufour, Catherine; Henry, Brook L.; Montoya, Jessica; Gouaux, Ben; Moore, Raeanne C.; Letendre., Scott L.; Woods, Steven Paul; Grant, Igor; Jeste, Dilip V.; Moore, David J.

    2015-01-01

    We examined the association between physical activity (PA), neurocognitive impairment (NCI), and instrumental activities of daily living (IADLs) among older HIV+ persons. One hundred older HIV+ adults completed the International Physical Activity Questionnaire (IPAQ), a neurocognitive battery, and IADL scale. Higher levels of moderate PA were associated with lower odds of NCI (p=0.01), even when covariates were modeled. The association between moderate PA and NCI was driven by executive function (p=0.04). Higher levels of moderate PA were also associated with lower odds of IADL Dependence (p = 0.03), although this fell to a trend (p = 0.08) when including covariates. Follow-up analysis showed those with both NCI and IADL Dependence had lower moderate PA than those with neither (p=0.03). While these cross-sectional findings suggest PA is associated with better neurocognitive and everyday functioning in older HIV+ adults, longitudinal studies utilizing objective PA methods are needed to evaluate directionality and mechanisms. PMID:25731660

  12. Renal ischemia/reperfusion injury: functional tissue preservation by anti-activated {beta}1 integrin therapy.

    PubMed

    Molina, Ana; Ubeda, María; Escribese, María M; García-Bermejo, Laura; Sancho, David; Pérez de Lema, Guillermo; Liaño, Fernando; Cabañas, Carlos; Sánchez-Madrid, Francisco; Mampaso, Francisco

    2005-02-01

    Renal ischemia/reperfusion injury (IRI) is an important cause of acute renal failure. Cellular and molecular responses of the kidney to IRI are complex and not fully understood. beta1 integrins localize to the basal surface of tubular epithelium interacting with extracellular matrix components of the basal membrane, including collagen IV. Whether preservation of tubular epithelium integrity could be a therapeutic approach for IRI was assessed. The effects of HUTS-21 mAb administration, which recognizes an activation-dependent epitope of beta1 integrins, in a rat model of IRI were investigated. Preischemic HUTS-21 administration resulted in the preservation of renal functional and histopathologic parameters. Analyses of activated beta1 integrins expression and focal adhesion kinase phosphorylation suggest that its deactivation after IRI was prevented by HUTS-21 treatment. Moreover, HUTS-21 impaired the inflammatory response in vivo, as indicated by inhibition of proinflammatory mediators and the absence of infiltrating cells. Ex vivo adhesion assays using reperfused kidneys revealed that HUTS-21 induced a significant increase of epithelial cell attachment to collagen IV. In conclusion, the data provide evidence that HUTS-21 has a protective effect in renal IRI, preventing tubular epithelial cell detachment by preserving activated beta1 integrins functions.

  13. Time delays and capability of elderly to activate speaker function for continuous telephone CPR

    PubMed Central

    2013-01-01

    Background Telephone-CPR (T-CPR) can increase rate of bystander CPR as well as CPR quality. Instructions for T-CPR were developed when most callers used a land line. Telephones today are often wireless and can be brought to the patient. They often have speaker function which further allows the rescuer to receive instructions while performing CPR. We wanted to measure adult lay people’s ability to activate the speaker function on their own mobile phone. Methods Elderly lay people, previously trained in CPR, were contacted by telephone. Participants with speaker function experience were asked to activate this without further instructions, while participants with no experience were given instructions on how to activate it. Participants were divided in three groups; Group 1: Can activate the speaker function without instruction, Group 2: Can activate the speaker function with instruction, and Group 3: Unable to activate the speaker function. Time to activation for group 1 and 2 was compared using Mann-Whitney U-test. Results Seventy-two elderly lay people, mean age 68 ± 6 years participated in the study. Thirty-five (35)% of the participants were able to activate the speaker function without instructions, 29% with instructions and 36% were unable to activate the speaker function. The median time to activate the speaker function was 8s and 93s, with and without instructions, respectively (p < 0.01). Conclusion One-third of the elderly could activate speaker function quickly, and two-third either used a long time or could not activate the function. PMID:23676015

  14. Spatial Correlation Function of the Chandra Selected Active Galactic Nuclei

    NASA Technical Reports Server (NTRS)

    Yang, Y.; Mushotzky, R. F.; Barger, A. J.; Cowie, L. L.

    2006-01-01

    We present the spatial correlation function analysis of non-stellar X-ray point sources in the Chandra Large Area Synoptic X-ray Survey of Lockman Hole Northwest (CLASXS). Our 9 ACIS-I fields cover a contiguous solid angle of 0.4 deg(exp 2) and reach a depth of 3 x 10(exp -15) erg/square cm/s in the 2-8 keV band. We supplement our analysis with data from the Chandra Deep Field North (CDFN). The addition of this field allows better probe of the correlation function at small scales. A total of 233 and 252 sources with spectroscopic information are used in the study of the CLASXS and CDFN fields respectively. We calculate both redshift-space and projected correlation functions in co-moving coordinates, averaged over the redshift range of 0.1 < z < 3.0, for both CLASXS and CDFN fields for a standard cosmology with Omega(sub Lambda) = 0.73,Omega(sub M) = 0.27, and h = 0.71 (H(sub 0) = 100h km/s Mpc(exp -1). The correlation function for the CLASXS field over scales of 3 Mpc< s < 200 Mpc can be modeled as a power-law of the form xi(s) = (S/SO)(exp - gamma), with gamma = 1.6(sup +0.4 sub -0.3) and S(sub o) = 8.0(sup +.14 sub -1.5) Mpc. The redshift-space correlation function for CDFN on scales of 1 Mpc< s < 100 Mpc is found to have a similar correlation length so = 8.55(sup +0.74 sub -0.74) Mpc, but a shallower slope (gamma = 1.3 +/- 0.1). The real-space correlation functions derived from the projected correlation functions, are found to be tau(sub 0 = 8.1(sup +1.2 sub -2.2) Mpc, and gamma = 2.1 +/- 0.5 for the CLASXS field, and tau(sub 0) = 5.8(sup +.1.0 sub -1.5) Mpc, gamma = 1.38(sup +0.12 sub -0.14 for the CDFN field. By comparing the real- and redshift-space correlation functions in the combined CLASXS and CDFN samples, we are able to estimate the redshift distortion parameter Beta = 0.4 +/- 0.2 at an effective redshift z = 0.94. We compare the correlation functions for hard and soft spectra sources in the CLASXS field and find no significant difference between the

  15. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  16. MifM Monitors Total YidC Activities of Bacillus subtilis, Including That of YidC2, the Target of Regulation

    PubMed Central

    Ito, Koreaki

    2014-01-01

    The YidC/Oxa1/Alb3 family proteins are involved in membrane protein biogenesis in bacteria, mitochondria, and chloroplasts. Recent studies show that YidC uses a channel-independent mechanism to insert a class of membrane proteins into the membrane. Bacillus subtilis has two YidC homologs, SpoIIIJ (YidC1) and YidC2 (YqjG); the former is expressed constitutively, while the latter is induced when the SpoIIIJ activity is compromised. MifM is a substrate of SpoIIIJ, and its failure in membrane insertion is accompanied by stable ribosome stalling on the mifM-yidC2 mRNA, which ultimately facilitates yidC2 translation. While mutational inactivation of SpoIIIJ has been known to induce yidC2 expression, here, we show that the level of this induction is lower than that observed when the membrane insertion signal of MifM is defective. Moreover, this partial induction of YidC2 translation is lowered further when YidC2 is overexpressed in trans. These results suggest that YidC2 is able to insert MifM into the membrane and to release its translation arrest. Thus, under SpoIIIJ-deficient conditions, YidC2 expression is subject to MifM-mediated autogenous feedback repression. Our results show that YidC2 uses a mechanism that is virtually identical to that used by SpoIIIJ; Arg75 of YidC2 in its intramembrane yet hydrophilic cavity is functionally indispensable and requires negatively charged residues of MifM as an insertion substrate. From these results, we conclude that MifM monitors the total activities of the SpoIIIJ and the YidC2 pathways to control the synthesis of YidC2 and to maintain the cellular capability of the YidC mode of membrane protein biogenesis. PMID:25313395

  17. Management with willow short rotation coppice increase the functional gene diversity and functional activity of a heavy metal polluted soil.

    PubMed

    Xue, K; van Nostrand, J D; Vangronsveld, J; Witters, N; Janssen, J O; Kumpiene, J; Siebielec, G; Galazka, R; Giagnoni, L; Arenella, M; Zhou, J-Z; Renella, G

    2015-11-01

    We studied the microbial functional diversity, biochemical activity, heavy metals (HM) availability and soil toxicity of Cd, Pb and Zn contaminated soils, kept under grassland or short rotation coppice (SRC) to attenuate the risks associated with HM contamination and restore the soil ecological functions. Soil microbial functional diversity was analyzed by the GeoChip, a functional gene microarray containing probes for genes involved in nutrient cycling, metal resistance and stress response. Soil under SRC showed a higher abundance of microbial genes involved in C, N, P and S cycles and resistance to various HM, higher microbial biomass, respiration and enzyme activity rates, and lower HM availability than the grassland soil. The linkages between functional genes of soil microbial communities and soil chemical properties, HM availability and biochemical activity were also investigated. Soil toxicity and N, P and Pb availability were important factors in shaping the microbial functional diversity, as determined by CCA. We concluded that in HM contaminated soils the microbial functional diversity was positively influenced by SRC management through the reduction of HM availability and soil toxicity increase of nutrient cycling. The presented results can be important in predicting the long term environmental sustainability of plant-based soil remediation.

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

    PubMed Central

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

    2012-01-01

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

  19. Temporal dynamics of activation of thematic and functional knowledge during conceptual processing of manipulable artifacts.

    PubMed

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

    2012-09-01

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

  20. Emergent Public Spaces: Generative Activities on Function Interpolation

    ERIC Educational Resources Information Center

    Carmona, Guadalupe; Dominguez, Angeles; Krause, Gladys; Duran, Pablo

    2011-01-01

    This study highlights ways in which generative activities may be coupled with network-based technologies in the context of teacher preparation to enhance preservice teachers' cognizance of how their own experience as students provides a blueprint for the learning environments they may need to generate in their future classrooms. In this study, the…

  1. The effect of ageing on platelet function and fibrinolytic activity.

    PubMed

    Gleerup, G; Winther, K

    1995-08-01

    Twelve healthy male volunteers, mean age twenty-five, range twenty-one to thirty years, and 12 healthy middle-aged male volunteers mean age fifty-eight, range forty-four to seventy-two years, were tested regarding platelet aggregation induced by adenosine diphosphate and fibrinolytic activity, estimated as euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA), and the fast-acting inhibitor against t-PA normally referred to as (PAI-1). Platelet aggregation increased significantly in the middle-aged group as compared with the young, as shown by a decrease in ADP thresholds for irreversible aggregation (P < 0.01). In healthy young volunteers, vigorous cycling exercise by itself caused platelet aggregability to decrease (P < 0.05). Such changes were not observed in the elderly. Fibrinolytic activity decreased significantly in the middle-aged group as shown by a prolongation of the ECLT (P < 0.01) and PAI-1, although not significantly, increased by approximately 100%, whereas t-PA significantly increased in the middle-aged group (P < 0.01). The present results suggest that increasing age is associated with not only increased platelet aggregability but also decreased fibrinolytic activity.

  2. Functionally charged nanosize particles differentially activate BV2 microglia.

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or p...

  3. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  4. Compaction, Fusion, and Functional Activation of Three-Dimensional Human Mesenchymal Stem Cell Aggregate

    PubMed Central

    Tsai, Ang-Chen; Liu, Yijun; Yuan, Xuegang

    2015-01-01

    Human mesenchymal stem cells (hMSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, hMSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates that improve a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. While cell–cell contacts and cell–extracellular matrix interactions mediate 3D cell aggregation, the adaptive changes of hMSC cytoskeleton during self-assembly and associated metabolic reconfiguration may also influence aggregate properties and functional activation. In this study, we investigated the role of actin in regulating 3D hMSC aggregate compaction, fusion, spreading and functional activation. Individual hMSC aggregates with controlled initial cell number were formed by seeding a known number of hMSCs (500, 2000, and 5000 cells/well) in multi-well plates of an ultra-low adherent surface to form multicellular aggregates in individual wells. To assess the influence of actin-mediated contractility on hMSC aggregation and properties, actin modulators, including cytochalasin D (cytoD), nocodazole, lysophosphatidic acid (LPA), and Y-27632, were added at different stages of aggregation and their impacts on hMSC aggregate compaction and apoptosis were monitored. The results suggest that actin-mediated contractility influences hMSC aggregation, compaction, fusion, and spreading on adherent surface. Formation of multi-cellular aggregates significantly upregulated caspase 3/7 expression, expression of C-X-C chemokine receptor type 4 (CXCR-4), cell migration, secretion of prostaglandin E2 (PGE-2) and interleukin 6 (IL-6), and resistance to in vitro ischemic stress. The functional enhancement, however, is dependent on caspase activation, because treatment with Q-VD-OPh, a pan

  5. Two functional polymorphisms of ROCK2 enhance arterial stiffening through inhibiting its activity and expression.

    PubMed

    Liao, Yi-Chu; Liu, Ping-Yen; Lin, Hsiu-Fen; Lin, Wen-Yi; Liao, James K; Juo, Suh-Hang H

    2015-02-01

    Derangement of Rho-associated kinases (ROCKs) has been related to coronary artery disease and stroke. ROCK2, rather than ROCK1, plays a predominant role in vascular contractility. The present study aims to test (1) the associations between ROCK2 single nucleotide polymorphisms (SNPs) and arterial stiffness, and (2) the molecular mechanism accounting for their effects. Stiffness parameters including beta (β), elasticity modulus (Ep) and pulse wave velocity (PWV) were obtained by carotid ultrasonography. Seven tagging SNPs of ROCK2 were initially genotyped in 856 subjects and significant SNPs were replicated in another group of 527 subjects. Two SNPs in complete linkage disequilibrium were found to be significantly associated with arterial stiffness. The major alleles of rs978906 (A allele) and rs9808232 (C allele) were associated with stiffer arteries. SNP rs978906 was predicted to influence microRNA(miR)-1183 binding to ROCK2, while rs9808232 causes amino acid substitution. To determine their functional impact, plasmid constructs carrying different alleles of the significant SNPs were created. Compared to rs978906G-allele constructs, cells transfected with rs978906A-allele constructs had higher baseline luciferase activities and were less responsive to miR-1183 changes. Oxidized-low density lipoprotein (Ox-LDL) suppressed miR-1183 levels and increased ROCK2 protein amounts. For rs9808232, cells transfected with C-allele constructs had significantly higher ROCK activities than those with A-allele constructs. Leukocyte ROCK activities were further measured in 52 healthy subjects. The average ROCK activity was highest in human subjects with CC genotype at rs9808232, followed by those with AC and lowest in AA. Taken together, the present study showed that two functional SNPs of ROCK2 increase susceptibility of arterial stiffness in the Chinese population. Non-synonymous SNP rs9808232 influences ROCK2 activity, while 3' UTR SNP rs978906 affects the ROCK2 protein

  6. Two functional polymorphisms of ROCK2 enhance arterial stiffening through inhibiting its activity and expression

    PubMed Central

    Liao, Yi-Chu; Liu, Ping-Yen; Lin, Hsiu-Fen; Lin, Wen-Yi; Liao, James K.; Juo, Suh-Hang H.

    2016-01-01

    Derangement of Rho-associated kinases (ROCKs) has been related to coronary artery disease and stroke. ROCK2, rather than ROCK1, plays a predominant role in vascular contractility. The present study aims to test (1) the associations between ROCK2 single nucleotide polymorphisms (SNPs) and arterial stiffness, and (2) the molecular mechanism accounting for their effects. Stiffness parameters including beta (β), elasticity modulus (Ep) and pulse wave velocity (PWV) were obtained by carotid ultrasonography. Seven tagging SNPs of ROCK2 were initially genotyped in 856 subjects and significant SNPs were replicated in another group of 527 subjects. Two SNPs in complete linkage disequilibrium were found to be significantly associated with arterial stiffness. The major alleles of rs978906 (A allele) and rs9808232 (C allele) were associated with stiffer arteries. SNP rs978906 was predicted to influence microRNA(miR)-1183 binding to ROCK2, while rs9808232 causes amino acid substitution. To determine their functional impact, plasmid constructs carrying different alleles of the significant SNPs were created. Compared to rs978906G-allele constructs, cells transfected with rs978906A-allele constructs had higher baseline luciferase activities and were less responsive to miR-1183 changes. Oxidized-low density lipoprotein (Ox-LDL) suppressed miR-1183 levels and increased ROCK2 protein amounts. For rs9808232, cells transfected with C-allele constructs had significantly higher ROCK activities than those with A-allele constructs. Leukocyte ROCK activities were further measured in 52 healthy subjects. The average ROCK activity was highest in human subjects with CC genotype at rs9808232, followed by those with AC and lowest in AA. Taken together, the present study showed that two functional SNPs of ROCK2 increase susceptibility of arterial stiffness in the Chinese population. Non-synonymous SNP rs9808232 influences ROCK2 activity, while 3' UTR SNP rs978906 affects the ROCK2 protein

  7. Mirror neuron activation in children with developmental coordination disorder: A functional MRI study.

    PubMed

    Reynolds, Jess E; Licari, Melissa K; Billington, Jac; Chen, Yihui; Aziz-Zadeh, Lisa; Werner, Julie; Winsor, Anne M; Bynevelt, Michael

    2015-12-01

    The aim of this study was to reveal cortical areas that may contribute to the movement difficulties seen in children with Developmental Coordination Disorder (DCD). Specifically, we hypothesized that there may be a deficit in the mirror neuron system (MNS), a neural system that responds to both performed and observed actions. Using functional MRI, 14 boys with DCD (x=10.08 years ± 1.31, range=7.83-11.58 years) and 12 typically developing controls (x=10.10 years ± 1.15, range=8.33-12.00 years) were scanned observing, executing and imitating a finger sequencing task using their right hand. Cortical activations of mirror neuron regions, including posterior inferior frontal gyrus (IFG), ventral premotor cortex, anterior inferior parietal lobule and superior temporal sulcus were examined. Children with DCD had decreased cortical activation mirror neuron related regions, including the precentral gyrus and IFG, as well as in the posterior cingulate and precuneus complex when observing the sequencing task. Region of interest analysis revealed lower activation in the pars opercularis, a primary MNS region, during imitation in the DCD group compared to controls. These findings provide some preliminary evidence to support a possible MNS dysfunction in children with DCD. PMID:26523778

  8. Relations between Recent Past Leisure Activities with Risks of Dementia and Cognitive Functions after Stroke

    PubMed Central

    Wong, Adrian; Lau, Alexander Y. L.; Lo, Eugene; Tang, Michael; Wang, Zhaolu; Liu, Wenyan; Tanner, Nicole; Chau, Natalie; Law, Lorraine; Shi, Lin; Chu, Winnie C. W.; Yang, Jie; Xiong, Yun-yun; Lam, Bonnie Y. K.; Au, Lisa; Chan, Anne Y. Y.; Soo, Yannie; Leung, Thomas W. H.; Wong, Lawrence K. S.; Lam, Linda C. W.; Mok, Vincent C. T.

    2016-01-01

    Background Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. Methods Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3–6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3–6 months after stroke. Results Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20–0.63) and stretching & toning physical exercise (0.37, 0.21–0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. Conclusions Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive

  9. How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs.

    PubMed

    Acuna, Claudio; Liu, Xinran; Südhof, Thomas C

    2016-08-17

    RIMs and RIM-binding proteins (RBPs) are evolutionary conserved multidomain proteins of presynaptic active zones that are known to recruit Ca(2+) channels; in addition, RIMs perform well-recognized functions in tethering and priming synaptic vesicles for exocytosis. However, deletions of RIMs or RBPs in mice cause only partial impairments in various active zone functions and have no effect on active zone structure, as visualized by electron micrographs, suggesting that their contribution to active zone functions is limited. Here, we show in synapses of the calyx of Held in vivo and hippocampal neurons in culture that combined, but not individual, deletions of RIMs and RBPs eliminate tethering and priming of synaptic vesicles, deplete presynaptic Ca(2+) channels, and ablate active zone complexes, as analyzed by electron microscopy of chemically fixed synapses. Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions. PMID:27537484

  10. How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs.

    PubMed

    Acuna, Claudio; Liu, Xinran; Südhof, Thomas C

    2016-08-17

    RIMs and RIM-binding proteins (RBPs) are evolutionary conserved multidomain proteins of presynaptic active zones that are known to recruit Ca(2+) channels; in addition, RIMs perform well-recognized functions in tethering and priming synaptic vesicles for exocytosis. However, deletions of RIMs or RBPs in mice cause only partial impairments in various active zone functions and have no effect on active zone structure, as visualized by electron micrographs, suggesting that their contribution to active zone functions is limited. Here, we show in synapses of the calyx of Held in vivo and hippocampal neurons in culture that combined, but not individual, deletions of RIMs and RBPs eliminate tethering and priming of synaptic vesicles, deplete presynaptic Ca(2+) channels, and ablate active zone complexes, as analyzed by electron microscopy of chemically fixed synapses. Thus, RBPs perform unexpectedly broad roles at the active zone that together with those of RIMs are essential for all active zone functions.

  11. Effects of single- and multiday ozone exposures on respiratory function in active normal children

    SciTech Connect

    Spektor, D.M.; Thurston, G.D.; Mao, J.; He, D.; Hayes, C.; Lippmann, M. )

    1991-08-01

    Ventilatory function was measured twice daily on 46 healthy children aged 8-14 years on at least 7 days for each child during a 4-week period at a northwestern New Jersey residential summer camp in 1988. The highest 1-hr O3 concentration was 150 ppb, while the highest 12-hr H+ concentration (as H2SO4) was 18.6 micrograms/m3. The highest temperature-humidity index was 81 degrees F. The regressions of FVC, FEV1, FEF25-75, and PEFR on O3 in the hour preceding the afternoon function measurements yielded slopes essentially the same as those measured on other children at the same camp in 1984. Regressions of the changes in function between the late morning and late afternoon function measurements on average O3 concentration between them produced significant, but somewhat smaller effects, while regressions of morning function on O3 during the previous day indicated small but still significant effects. There were no significant correlations with other measured environmental variables including H+. Based on the results of this study and similar previous studies, we conclude that O3 exposures in ambient air produce greater lung function deficits in active young people in natural settings then does pure O3 in controlled chamber exposure studies because of: (1) longer exposures; (2) potentiation by other factors in the ambient exposures; (3) the persistence of effects from prior day's exposures; and (4) the persistence of a transient response associated with the daily peak of exposure. It follows that projections of likely effects in the real world from controlled chamber exposure studies should either have a large margin of safety, or the judgment of the extent of effects likely to occur among populations should be based directly on the effects observed in field studies.

  12. Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine.

    PubMed

    Wilcox, Sophie L; Veggeberg, Rosanna; Lemme, Jordan; Hodkinson, Duncan J; Scrivani, Steven; Burstein, Rami; Becerra, Lino; Borsook, David

    2016-01-01

    Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification.

  13. Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine

    PubMed Central

    Wilcox, Sophie L.; Veggeberg, Rosanna; Lemme, Jordan; Hodkinson, Duncan J.; Scrivani, Steven; Burstein, Rami; Becerra, Lino; Borsook, David

    2016-01-01

    Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification. PMID:27507939

  14. Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine.

    PubMed

    Wilcox, Sophie L; Veggeberg, Rosanna; Lemme, Jordan; Hodkinson, Duncan J; Scrivani, Steven; Burstein, Rami; Becerra, Lino; Borsook, David

    2016-01-01

    Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification. PMID:27507939

  15. Functionalization, cyclization and antiviral activity of A-secotriterpenoids.

    PubMed

    Grishko, Victoria V; Galaiko, Natalia V; Tolmacheva, Irina A; Kucherov, Igor I; Eremin, Vladimir F; Boreko, Eugene I; Savinova, Olga V; Slepukhin, Pavel A

    2014-08-18

    Triterpene derivatives with an α,β-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses - influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.9-18.2 μM) and HIV-1 (EC50 0.06 μM) were the most promising compounds. PMID:24997292

  16. Characterization of functionally active subribosomal particles from Thermus aquaticus

    PubMed Central

    Khaitovich, Philipp; Mankin, Alexander S.; Green, Rachel; Lancaster, Laura; Noller, Harry F.

    1999-01-01

    Peptidyl transferase activity of Thermus aquaticus ribosomes is resistant to the removal of a significant number of ribosomal proteins by protease digestion, SDS, and phenol extraction. To define the upper limit for the number of macromolecular components required for peptidyl transferase, particles obtained by extraction of T. aquaticus large ribosomal subunits were isolated and their RNA and protein composition was characterized. Active subribosomal particles contained both 23S and 5S rRNA associated with notable amounts of eight ribosomal proteins. N-terminal sequencing of the proteins identified them as L2, L3, L13, L15, L17, L18, L21, and L22. Ribosomal protein L4, which previously was thought to be essential for the reconstitution of particles active in peptide bond formation, was not found. These findings, together with the results of previous reconstitution experiments, reduce the number of possible essential macromolecular components of the peptidyl transferase center to 23S rRNA and ribosomal proteins L2 and L3. Complete removal of ribosomal proteins from T. aquaticus rRNA resulted in loss of tertiary folding of the particles and inactivation of peptidyl transferase. The accessibility of proteins in active subribosomal particles to proteinase hydrolysis was increased significantly after RNase treatment. These results and the observation that 50S ribosomal subunits exhibited much higher resistance to SDS extraction than 30S subunits are compatible with a proposed structural organization of the 50S subunit involving an RNA “cage” surrounding a core of a subset of ribosomal proteins. PMID:9874776

  17. Results of a workshop concerning impacts of various activities on the functions of bottomland hardwoods

    USGS Publications Warehouse

    Roelle, James E.; Auble, Gregor T.; Hamilton, David B.; Horak, Gerald C.; Johnson, Richard L.; Segelquist, Charles A.

    1987-01-01

    Under Section 404 of the Clean Water Act, the U.S. Environmental Protection Agency (EPA) has regulatory responsibilities related to the discharge of dredged or fill material into the Nation’s waters. In addition to its advisory role in the U.S. Army Corps of Engineers' permit program, EPA has a number of specific authorities, including formulation of the Section 404(b)(1) guidelines, use of Section 404(c) to prohibit disposal at particular sites, and enforcement actions for unauthorized discharges. A number of recent court cases focus on the geographic scope of Section 404 jurisdiction in potential bottomland hardwood (BLH) wetlands and the nature of landclearing activities in these areas that require a permit under Section 404. Accordingly, EPA needs to establish the scientific basis for implementing its responsibilities under Section 404 in bottomland hardwoods. EPA is approaching this task through a series of workshops designed to provide current scientific information on bottomland hardwoods and to organize that information in a manner pertinent to key policy questions. The first two workshops in the series were originally conceived as technically oriented meetings that would provide the information necessary to develop policy options at the third workshop. More specifically, the first workshop was designed to examine a zonation concept as a means of characterizing different BLH communities and describing variations in their functions along a soil moisture gradient. The second workshop was perceived as an attempt to evaluate the impacts of various activities on those functions. However, one conclusion of the first workshop, which was held in December 1984 in St. Francisville, Louisiana, was that the zonation approach does not describe the variability in the functions performed by BLH ecosystems sufficiently well to allow its use as the sole basis for developing a regulatory framework. That is, factors other than zone were considered critical for an effective

  18. Nanoscale friction as a function of activation energies

    NASA Astrophysics Data System (ADS)

    Chong, W. W. F.; Rahnejat, H.

    2015-12-01

    Understanding the scale-dependence of friction is increasingly viewed as a critical quest. With progressively thinner films, mixed and boundary regimes of lubrication have become commonplace. Therefore, at the micro-scale a greater need for mitigating friction is desired in order to improve operational efficiency of many machines and mechanisms. Furthermore, there is a growing tendency to use low friction hard wear-resistant advanced coatings to guard against wear. In parallel, there has been much attention paid to lubricant rheology and formulation. However, only in recent times there has been an emerging view of lubricant-surface combination as a system. In this perspective it is essential to relate the observed and measured friction at component level to the underlying interactions in micro/nano-scales. This is the approach in this paper. Observed phenomenon at micro-scale are related back to the activation energies of lubricant-surface system, providing in particular results for surface modified Ni-SiC coated specimen in combination with formulated lubricants, the combination of which represent the lubricant-surface system of choice in cylinders of high performance race engine. The nano-scale conjunction of an AFM tip with lubricated surface-engineered specimen, subjected to various conjunctional loading and sliding kinematics is investigated. It is shown that the measured frictional characteristics can be adequately described in terms of activation energies in line with the Eyring’s thermal activation model for cases of fairly smooth asperity tip contact conjunctions.

  19. Fluctuations in Neuronal Activity: Clues to Brain Function

    NASA Astrophysics Data System (ADS)

    Pérez Velazquez, José L.; Guevara, Ramón; Belkas, Jason; Wennberg, Richard; Senjanoviè, Goran; García Dominguez, Luis

    2005-08-01

    Recordings from neuronal preparations, either in vitro or in the intact brain, are characterized by fluctuations, what is commonly considered as "noise". Due to the current recording and analysis methods, it is not feasible to separate what we term noise, from the "meaningful" neuronal activity. We propose that fluctuations serve to maintain brain activity in an optimal state for cognitive processing, not allowing it to fall into long-term periodic behaviour. We have studied fluctuations in magnetoencephalographic (MEG) recordings from normal subjects and epileptic patients, in electroencephalographic (EEG) recordings from children with impact injury, as well as in intracerebral electrophysiological recordings in freely moving rats. Specifically, we have determined phase locking patterns between brain areas from these recordings, which display fluctuations at different scales. We submit the idea that the variability in phase synchronization affords a more complete search of all possible phase differences in a hypothetical phase-locking state space that contributes to brain information processing. In brain pathologies, like epileptiform activity here studied, different levels of fluctuations in phase synchrony may favour the generation of stable synchronized states that characterize epileptic seizures. While the border between noise and high-dimensional dynamics is fuzzy, the scrutiny of neuronal fluctuations at different levels will provide important insights to the unravelling of the relation between brain and behaviour.

  20. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function.

    PubMed

    Dutta, Arnob; Abmayr, Susan M; Workman, Jerry L

    2016-08-18

    Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs. PMID:27540855

  1. Suicidal ideation and its determinants in Korean adults: The role of physical activity and functional limitations.

    PubMed

    Park, S M

    2015-01-01

    The recognition of suicide as a major public health problem has suggested the need to identify risk factors that have implications for preventive intervention. In the suicidal process, suicidal ideation is a key stage in the pathway leading to eventual suicide. This study investigated the influence of physical activity and functional limitations on suicidal ideation among young and middle-aged adults in a high suicidal society. Data for the current study were obtained from the Fourth Korea National Health and Nutrition Examination Survey 2007-2009 (KNHANES), a cross-sectional study conducted by the Korea Centers for Disease Control and Prevention. The survey conducted face-to-face interviews with young adults (n = 2326) and middle-aged adults (n = 3396). Using multivariate logistic regression analysis, the relationship of physical activity and functional limitations with suicidal ideation in young and middle-aged adults was assessed. A notable outcome was that the absence of a regular walking was correlated with increased suicidal ideation in middle-aged women. The other major finding was that young women and middle-aged adults with functional limitations had a high rate of suicidal thoughts. Multiple intervention approaches, including informational, social and behavioural approaches, are needed to promote regular walking in middle-aged women. For instance, mass media campaigns, community walking groups and individually adapted health behaviour modification may provide opportunities for positive intervention. Additionally, another important public health implication from these findings is the need for a suicide-intervention support system that includes screening for suicide risk in healthcare settings, especially among young women with physical limitations. PMID:25434531

  2. The nuclear factor SPBP contains different functional domains and stimulates the activity of various transcriptional activators.

    PubMed

    Rekdal, C; Sjøttem, E; Johansen, T

    2000-12-22

    SPBP (stromelysin-1 platelet-derived growth factor-responsive element binding protein) was originally cloned from a cDNA expression library by virtue of its ability to bind to a platelet-derived growth factor-responsive element in the human stromelysin-1 promoter. A 937-amino acid-long protein was deduced from a 3995-nucleotide murine cDNA sequence. By analyses of both human and murine cDNAs, we now show that SPBP is twice as large as originally found. The human SPBP gene contains six exons and is located on chromosome 22q13.1-13.3. Two isoforms differing in their C termini are expressed due to alternative splicing. PCR analyses of multitissue cDNA panels showed that SPBP is expressed in most tissues except for ovary and prostate. Functional mapping revealed that SPBP is a nuclear, multidomain protein containing an N-terminal region with transactivating ability, a novel type of DNA-binding domain containing an AT hook motif, and a bipartite nuclear localization signal as well as a C-terminal zinc finger domain. This type of zinc finger domain is also found in the trithorax family of chromatin-based transcriptional regulator proteins. Using cotransfection experiments, we find that SPBP enhances the transcriptional activity of various transcription factors such as c-Jun, Ets1, Sp1, and Pax6. Hence, SPBP seems to act as a transcriptional coactivator. PMID:10995766

  3. 34 CFR 303.15 - Include; including.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Include; including. 303.15 Section 303.15 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  4. Physical Activity Play: The Nature and Function of a Neglected Aspect of Play.

    ERIC Educational Resources Information Center

    Pellegrini, A. D.; Smith, Peter K.

    1998-01-01

    Considers the nature and developmental functions of physical activity play. Distinguishes three kinds of physical activity play with consecutive age peaks: rhythmic stereotypies, exercise play, and rough-and-tumble play. Considers gender differences and function in terms of immediate and deferred consequences in physical, cognitive, and social…

  5. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes

    PubMed Central

    Blaker-Lee, Alicia; Gupta, Sunny; McCammon, Jasmine M.; De Rienzo, Gianluca; Sive, Hazel

    2012-01-01

    SUMMARY Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs), intellectual disability disorder (IDD) and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV). The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed ‘dosage sensors’), which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development – impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa) and kinesin family member 22 (kif22) genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least) two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD. PMID

  6. Effects of 7,12-dimethylbenz[a]anthracene on immune function and mixed-function oxygenase activity in the European starling

    SciTech Connect

    Trust, K.A.; Hooper, M.J. . Inst. of Wildlife and Environmental Toxicology); Fairbrother, A. . Environmental Research Lab.)

    1994-05-01

    Immune function and hepatic MFO activity were examined in adult and nestling starlings administered a synthetic PAH, 7,12-dimethylbenz[a]anthracene (DMBA). Methods used to examine the starling immune system included immunopathology, macrophage phagocytosis, lymphocyte blastogenesis to concanavalin A, and hemagglutination of sheep erythrocytes (SRBC). Concomitant investigations of MFO activity were conducted in starlings exposed to DMBA. Ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-depentylase (PROD) were used as indicators of hepatic MFO activity. Changes in MFO activity were compared to chemically altered immune responses following DMBA exposure. Subcutaneous exposure of adult starlings to 125 mg/kg DMBA resulted in suppression of lymphocyte blastogenesis and antibody production to SRBC. EROD and PROD activity were increased 2.8- and 3.4-fold, respectively. Lymphocyte blastogenesis was impaired in adult starlings orally exposed to 125 mg/kg DMBA. The immune system of nestling starlings exposed orally to 100 mg/kg DMBA was altered, as evidenced by decreased phagocytic ability of macrophages and inhibition of lymphocyte blastogenesis. Oral exposure to DMBA did not induce MFO activity in starlings of either age class. Effects of DMBA on immune function and MFO activity in starlings varied with the age of birds and route and length of chemical exposure.

  7. U.S. Geological Survey Scientific Activities in the Exploration of Antarctica: Introduction to Antarctica (Including USGS Field Personnel: 1946-59)

    USGS Publications Warehouse

    Tony K. Meunier Edited by Williams, Richard S.; Ferrigno, Jane G.

    2007-01-01

    3) significant changes that have occurred in Antarctic exploration and research since World War II will be discussed at the end of this report. Subsequent Open-File Reports will provide a year-by-year documentation of USGS scientific activities and accomplishments in Antarctica beginning with the post-IGY, 1959-60 research team. One Open-File Report is planned to be written for each field-based season. For an example of the series format, see Open-File Reports 2006-1113 (Meunier, 2007a) and 2006-1114 (Meunier, 2007b). This report is a companion document to Open-File Report 2006-1116 (Meunier, 2007c). The USGS mapping and science programs in Antarctica are among the longest continuously funded projects in the United States Antarctic Program (USAP). The 2005-06 field season is the 56th consecutive U.S. expedition in which USGS scientists have been participants, starting in 1946. USGS and the National Science Foundation (NSF) cooperation began with the establishment by NSF of the U.S. Antarctic (Research) Program [USA(R)P] in 1958-59 under Operation Deep Freeze IV (DF IV) and was given the responsibility for the principal coordination and management of all U.S. scientific activities in Antarctica in Deep Freeze 60 (DF 60) (1959-60). Financial support from NSF, mostly in the form of Memorandum of Understandings (MOUs) and Cooperative Agreements, extends back to this period and can be attributed to the need for accurate geologic, geophysical, and topographic base maps of specific field areas or regions where NSF-funded science projects were planned. The epoch of Antarctic exploration during the IGY was driven by science and, in a spirit of peaceful cooperation, the international scientific community wanted to limit military activities on the continent to logistical support (Meunier, 1979 [2007], p. 38). The USGS, a Federal civilian science agency in the Department of the Interior, has, since its founding in 1879, carried out numerous field-based national (and some

  8. Effects of Classroom Animal-Assisted Activities on Social Functioning in Children with Autism Spectrum Disorder

    PubMed Central

    McKenzie, Samantha J.; McCune, Sandra; Slaughter, Virginia

    2014-01-01

    Abstract Objective: The objective of this study was to implement and evaluate a classroom-based Animal-Assisted Activities (AAA) program on social functioning in children with autism spectrum disorder (ASD). Design: This was a multisite, control-to-intervention design study. Settings/location: The study was conducted in 41 classrooms in 15 schools in Brisbane, Australia. Subjects: Sixty-four (64) 5- to 12-year-old children diagnosed with ASD comprised the study group. Intervention: The AAA program consisted of 8 weeks of animal exposure in the school classroom in addition to 16 20-minute animal-interaction sessions. Outcome measures: Teacher- and parent-reported child behavior and social functioning were assessed through standardized instruments at three time points: upon study entry (Time 1), after an 8-week waiting period during the week prior to the AAA program (Time 2), and during the week following the 8-week AAA program (Time 3). Results: Significant improvements were identified in social functioning, including increases in social approach behaviors and social skills, and decreases in social withdrawal behaviors, from before to after the AAA program, but not during the waitlist period. Over half of parents also reported that participants demonstrated an increased interest in attending school during the program. Conclusions: Results demonstrate the feasibility and potential efficacy of a new classroom-based Animal-Assisted Activities model, which may provide a relatively simple and cost-effective means of helping educators and families to improve the social functioning of children with ASD. PMID:24156772

  9. Activation-Enabled Syntheses of Functionalized Pillar[5]arene Derivatives.

    PubMed

    Han, Jie; Hou, Xisen; Ke, Chenfeng; Zhang, Huacheng; Strutt, Nathan L; Stern, Charlotte L; Stoddart, J Fraser

    2015-07-01

    A series of regioselective di- and trifunctionalized pillar[5]arene derivatives have been synthesized by a deprotection-followed-by-activation strategy, and their constitutions have been established as a result of having access to their solid-state structures. De-O-methylation occurs in a stepwise manner at lower temperatures under kinetic control, affording the desired oligo-substituted pillar[5]arene derivatives. In addition, the regioisomers of these derivatives can be isolated by installing triflate groups on the free hydroxyl groups. PMID:26083303

  10. Functionalized formazans: A review on recent progress in their pharmacological activities

    PubMed Central

    Shawali, Ahmad S.; Samy, Nevien A.

    2014-01-01

    This review provides an up to date information about the diverse pharmaceutical activities of formazans. The bibliography includes 97 references which have been published during the period from 1980 to 2013. The covered biological activities of the title compounds include antioxidant, anticonvulsant, therapeutic, anthelmintic, anti-tubercular, antiviral, anti-inflammatory, anticancer, anti-HIV, antimicrobial, antiparkinsonian, cardiovascular and antiproliferative activities. PMID:26257923

  11. [The brain structures functional activity and aggression patients' multiple sclerosis].

    PubMed

    Reznikova, T N; Seliverstova, N A; Kataeva, G V; Aroev, R A; Il'ves, A G; Kuznetsova, A K

    2015-01-01

    The article is devoted to investigation of unconscious aggression in patients with multiple sclerosis. We carried out comparison of the relative assessments of metabolism speed of glucose (according to positron emission tomography) and indicators of unconscious aggression (in the Hand test). It is shown that an increased tendency to open aggression (unconscious aggression) in patients with multiple sclerosis, is mainly linked with a reduction in the functioning of different departments of the frontal lobes of the brain on the left and with changes of the metabolism speed of glucose in the structures of the limbic system of the left and right hemisphere. With increasing of unconscious aggression we observed decrease of glucose metabolism speed in certain areas of the lower and middle frontal gyrus.

  12. Functionally relevant diversity of closely related Nitrospira in activated sludge

    PubMed Central

    Gruber-Dorninger, Christiane; Pester, Michael; Kitzinger, Katharina; Savio, Domenico F; Loy, Alexander; Rattei, Thomas; Wagner, Michael; Daims, Holger

    2015-01-01

    Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyze the second step of nitrification in most oxic habitats and are important for excess nitrogen removal from sewage in wastewater treatment plants (WWTPs). To date, little is known about their diversity and ecological niche partitioning within complex communities. In this study, the fine-scale community structure and function of Nitrospira was analyzed in two full-scale WWTPs as model ecosystems. In Nitrospira-specific 16S rRNA clone libraries retrieved from each plant, closely related phylogenetic clusters (16S rRNA identities between clusters ranged from 95.8% to 99.6%) within Nitrospira lineages I and II were found. Newly designed probes for fluorescence in situ hybridization (FISH) allowed the specific detection of several of these clusters, whose coexistence in the WWTPs was shown for prolonged periods of several years. In situ ecophysiological analyses based on FISH, relative abundance and spatial arrangement quantification, as well as microautoradiography revealed functional differences of these Nitrospira clusters regarding the preferred nitrite concentration, the utilization of formate as substrate and the spatial coaggregation with ammonia-oxidizing bacteria as symbiotic partners. Amplicon pyrosequencing of the nxrB gene, which encodes subunit beta of nitrite oxidoreductase of Nitrospira, revealed in one of the WWTPs as many as 121 species-level nxrB operational taxonomic units with highly uneven relative abundances in the amplicon library. These results show a previously unrecognized high diversity of Nitrospira in engineered systems, which is at least partially linked to niche differentiation and may have important implications for process stability. PMID:25148481

  13. Functionally relevant diversity of closely related Nitrospira in activated sludge.

    PubMed

    Gruber-Dorninger, Christiane; Pester, Michael; Kitzinger, Katharina; Savio, Domenico F; Loy, Alexander; Rattei, Thomas; Wagner, Michael; Daims, Holger

    2015-03-01

    Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyze the second step of nitrification in most oxic habitats and are important for excess nitrogen removal from sewage in wastewater treatment plants (WWTPs). To date, little is known about their diversity and ecological niche partitioning within complex communities. In this study, the fine-scale community structure and function of Nitrospira was analyzed in two full-scale WWTPs as model ecosystems. In Nitrospira-specific 16S rRNA clone libraries retrieved from each plant, closely related phylogenetic clusters (16S rRNA identities between clusters ranged from 95.8% to 99.6%) within Nitrospira lineages I and II were found. Newly designed probes for fluorescence in situ hybridization (FISH) allowed the specific detection of several of these clusters, whose coexistence in the WWTPs was shown for prolonged periods of several years. In situ ecophysiological analyses based on FISH, relative abundance and spatial arrangement quantification, as well as microautoradiography revealed functional differences of these Nitrospira clusters regarding the preferred nitrite concentration, the utilization of formate as substrate and the spatial coaggregation with ammonia-oxidizing bacteria as symbiotic partners. Amplicon pyrosequencing of the nxrB gene, which encodes subunit beta of nitrite oxidoreductase of Nitrospira, revealed in one of the WWTPs as many as 121 species-level nxrB operational taxonomic units with highly uneven relative abundances in the amplicon library. These results show a previously unrecognized high diversity of Nitrospira in engineered systems, which is at least partially linked to niche differentiation and may have important implications for process stability. PMID:25148481

  14. Executive Functions in Learning Processes: Do They Benefit from Physical Activity?

    ERIC Educational Resources Information Center

    Barenberg, Jonathan; Berse, Timo; Dutke, Stephan

    2011-01-01

    As executive functions play an essential role in learning processes, approaches capable of enhancing executive functioning are of particular interest to educational psychology. Recently, the hypothesis has been advanced that executive functioning may benefit from changes in neurobiological processes induced by physical activity. The present…

  15. A new approach to the determination of the stellate neuron activity function in rat's brain

    NASA Astrophysics Data System (ADS)

    Klymenko, O.; Oleinick, A.; Amatore, C.; Svir, I.

    2008-09-01

    In this work, we present the results of a mathematical modelling of NO· release by neurons and its transport in the brain by diffusion. The model is applied to analyze the experimental data on NO· release from a neuron monitored during its patch-clamp stimulation by an ultramicroelectrode introduced into a slice of living rat’s brain. The neuron activity function was obtained by numerical deconvolution of the experimental data using the response function of the electrode to an instantaneous spike of neuronal activity. The Gaussian decomposition of NO· release activity function allows qualitative and quantitative conclusions to be drawn about neuron activity. Since the integral activity function is readily obtained by deconvolution, the decomposition can be performed using other more relevant descriptions of NO· bursts emerging from active neurons.

  16. Variable Antibody-dependent Activation of Complement by Functionalized Phospholipid Nanoparticle Surfaces*

    PubMed Central

    Pham, Christine T. N.; Mitchell, Lynne M.; Huang, Jennifer L.; Lubniewski, Christopher M.; Schall, Otto F.; Killgore, J. Kendall; Pan, Dipanjan; Wickline, Samuel A.; Lanza, Gregory M.; Hourcade, Dennis E.

    2011-01-01

    A wide variety of nanomaterials are currently being developed for use in the detection and treatment of human diseases. However, there is no systematic way to measure and predict the action of such materials in biological contexts. Lipid-encapsulated nanoparticles (NPs) are a class of nanomaterials that includes the liposomes, the most widely used and clinically proven type of NPs. Liposomes can, however, activate the complement system, an important branch of innate immunity, resulting in undesirable consequences. Here, we describe the complement response to lipid-encapsulated NPs that are functionalized on the surface with various lipid-anchored gadolinium chelates. We developed a quantitative approach to examine the interaction of NPs with the complement system using in vitro assays and correlating these results with those obtained in an in vivo mouse model. Our results indicate that surface functionalization of NPs with certain chemical structures elicits swift complement activation that is initiated by a natural IgM antibody and propagated via the classical pathway. The intensity of the response is dependent on the chemical structures of the lipid-anchored chelates and not zeta potential effects alone. Moreover, the extent of complement activation may be tempered by complement inhibiting regulatory proteins that bind to the surface of NPs. These findings represent a step forward in the understanding of the interactions between nanomaterials and the host innate immune response and provide the basis for a systematic structure-activity relationship study to establish guidelines that are critical to the future development of biocompatible nanotherapeutics. PMID:21047788

  17. Effects of task-oriented training on upper extremity function and performance of daily activities by chronic stroke patients

    PubMed Central

    Park, JuHyung; Yoo, Chanuk

    2015-01-01

    [Purpose] The aim of this study was to determine the effects that task-oriented training has on upper extremity function and performance of daily activities by chronic stroke patients. [Subjects and Methods] Task-oriented training was applied to two chronic hemiplegic patients in this research. The training was provided to each patient for 30 minutes a day, five times a week for two weeks. The treatment program included six different types of training that could be performed by the patients themselves. Evaluation was performed four times, that is, once a week for three weeks before the intervention and once after the intervention. The change in upper extremity function was measured with the Manual Function Test, and the change in performance of daily activity was measured with the Functional Independence Measure. [Results] The upper extremity function of both subjects was improved after application of task-oriented training. However, in the performance of daily activities, subject one showed improvement compared to with before the intervention, whereas subject two showed the same results. [Conclusion] This research confirmed that two weeks of task-oriented training for chronic stroke patients is effective for improvement of upper extremity function and performance of daily activities by chronic stroke patients. PMID:26355425

  18. Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity with Reduced Impact on Islet β-Cell Function*

    PubMed Central

    Burke, Susan J.; May, Amanda L.; Noland, Robert C.; Lu, Danhong; Brissova, Marcela; Powers, Alvin C.; Sherrill, Elizabeth M.; Karlstad, Michael D.; Campagna, Shawn R.; Stephens, Jacqueline M.; Collier, J. Jason

    2015-01-01

    Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet β-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity. PMID:25851902

  19. Light, Including Ultraviolet

    PubMed Central

    Maverakis, Emanual; Miyamura, Yoshinori; Bowen, Michael P.; Correa, Genevieve; Ono, Yoko; Goodarzi, Heidi

    2009-01-01

    Ultraviolet (UV) light is intricately linked to the functional status of the cutaneous immune system. In susceptible individuals, UV radiation can ignite pathogenic inflammatory pathways leading to allergy or autoimmunity. In others, this same UV radiation can be used as a phototherapy to suppress pathogenic cutaneous immune responses. These vastly different properties are a direct result of UV light’s ability to ionize molecules in the skin and thereby chemically alter them. Sometimes these UV-induced chemical reactions are essential, the formation of pre-vitamin D3 from 7-dehydrocholesterol, for example. In other instances they can be potentially detrimental. UV radiation can ionize a cell’s DNA causing adjacent pyrimidine bases to chemically bond to each other. To prevent malignant transformation, a cell may respond to this UV-induced DNA damage by undergoing apoptosis. Although this pathway prevents skin cancer it also has the potential of inducing or exacerbating autoreactive immune responses by exposing the cell’s nuclear antigens. Ultaviolet-induced chemical reactions can activate the immune system by a variety of other mechanisms as well. In response to UV irradiation keratinocytes secrete cytokines and chemokines, which activate and recruit leukocytes to the skin. In some individuals UV-induced chemical reactions can synthesize novel antigens resulting in a photoallergy. Alternatively, photosensitizing molecules can damage cells by initiating sunburn-like phototoxic reactions. Herein we review all types of UV-induced skin reactions, especially those involving the immune system. PMID:20018479

  20. Assessing upper extremity motor function in practice of virtual activities of daily living.

    PubMed

    Adams, Richard J; Lichter, Matthew D; Krepkovich, Eileen T; Ellington, Allison; White, Marga; Diamond, Paul T

    2015-03-01

    A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user's avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman's rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs.

  1. Influence of physical activity and nutrition on obesity-related immune function.

    PubMed

    Huang, Chun-Jung; Zourdos, Michael C; Jo, Edward; Ormsbee, Michael J

    2013-01-01

    Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF- α , CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.

  2. Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

    PubMed Central

    Zourdos, Michael C.; Jo, Edward; Ormsbee, Michael J.

    2013-01-01

    Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation. PMID:24324381

  3. Kraft lignin/silica-AgNPs as a functional material with antibacterial activity.

    PubMed

    Klapiszewski, Łukasz; Rzemieniecki, Tomasz; Krawczyk, Magdalena; Malina, Dagmara; Norman, Małgorzata; Zdarta, Jakub; Majchrzak, Izabela; Dobrowolska, Anna; Czaczyk, Katarzyna; Jesionowski, Teofil

    2015-10-01

    Advanced functional silica/lignin hybrid materials, modified with nanosilver, were obtained. The commercial silica Syloid 244 was used, modified with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane to increase its chemical affinity to lignin. Similarly, kraft lignin was oxidized using a solution of sodium periodate to activate appropriate functional groups on its surface. Silver nanoparticles were grafted onto the resulting silica/lignin hybrids. The systems obtained were comprehensively tested using available techniques and methods, including transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, elemental analysis and atomic absorption spectroscopy. An evaluation was also made of the electrokinetic stability of the systems with and without silver nanoparticles. Conclusions were drawn concerning the chemical nature of the bonds between the precursors and the effectiveness of the method of binding nanosilver to the hybrid materials. The antimicrobial activity of the studied materials was tested against five species of Gram-positive and Gram-negative bacteria. The addition of silver nanoparticles to the silica/lignin hybrids led to inhibition of the growth of the analyzed bacteria. The best results were obtained against Pseudomonas aeruginosa, a dangerous human pathogen.

  4. Assessing upper extremity motor function in practice of virtual activities of daily living.

    PubMed

    Adams, Richard J; Lichter, Matthew D; Krepkovich, Eileen T; Ellington, Allison; White, Marga; Diamond, Paul T

    2015-03-01

    A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user's avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman's rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs. PMID:25265612

  5. Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

    PubMed Central

    Rubinger, Dvora; Backenroth, Rebecca; Sapoznikov, Dan

    2012-01-01

    Background The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. Methodology/Principal Findings Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of- dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. Conclusion/Significance Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated

  6. Mitochondrial activity and brain functions during cortical depolarization

    NASA Astrophysics Data System (ADS)

    Mayevsky, Avraham; Sonn, Judith

    2008-12-01

    Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

  7. Mind over age--stereotype activation and olfactory function.

    PubMed

    Miller, Stacie S; Gordon, Amy R; Olsson, Mats J; Lundström, Johan N; Dalton, Pamela

    2013-02-01

    Given that context affects olfaction and the elderly exhibit olfactory deficits, the current study tested whether a subtle change in internal context, evoked by priming the elderly stereotype, would affect performance in a variety of olfactory tasks including odor sensitivity, discrimination, and identification (Experiment 1), as well as perceived odor intensity, pleasantness and familiarity, and an odor reaction time task (Experiment 2). Such internalization of the elderly stereotype has been demonstrated with slower walking speeds and fewer words recalled in a memory task. In the current study, 76 participants first listened to a presentation about age-related declines in olfaction and then participated in 3 language tasks which, unbeknownst to them, served as the elderly stereotype priming manipulation. This priming manipulation was effective at decreasing walking speed and word recall, confirming the findings of previous researchers; however, olfaction was not affected. Whether olfaction is resistant to stereotype priming is discussed. PMID:23118205

  8. Effects of Lifestyle Interventions That Include a Physical Activity Component in Class II and III Obese Individuals: A Systematic Review and Meta-Analysis

    PubMed Central

    Baillot, Aurélie; Romain, Ahmed J.; Boisvert-Vigneault, Katherine; Audet, Mélisa; Baillargeon, Jean Patrice; Dionne, Isabelle J.; Valiquette, Louis; Chakra, Claire Nour Abou; Avignon, Antoine; Langlois, Marie-France

    2015-01-01

    Background In class II and III obese individuals, lifestyle intervention is the first step to achieve weight loss and treat obesity-related comorbidities before considering bariatric surgery. A systematic review, meta-analysis, and meta-regression were performed to assess the impact of lifestyle interventions incorporating a physical activity (PA) component on health outcomes of class II and III obese individuals. Methods An electronic search was conducted in 4 databases (Medline, Scopus, CINAHL and Sportdiscus). Two independent investigators selected original studies assessing the impact of lifestyle interventions with PA components on anthropometric parameters, cardiometabolic risk factors (fat mass, blood pressure, lipid and glucose metabolism), behaviour modification (PA and nutritional changes), and quality of life in adults with body mass index (BMI) ≥ 35 kg/m2. Estimates were pooled using a random-effect model (DerSimonian and Laird method). Heterogeneity between studies was assessed by the Cochran’s chi-square test and quantified through an estimation of the I². Results Of the 3,170 identified articles, 56 met our eligibility criteria, with a large majority of uncontrolled studies (80%). The meta-analysis based on uncontrolled studies showed significant heterogeneity among all included studies. The pooled mean difference in weight loss was 8.9 kg (95% CI, 10.2–7.7; p < 0.01) and 2.8 kg/m² in BMI loss (95% CI, 3.4–2.2; p < 0.01). Long-term interventions produced superior weight loss (11.3 kg) compared to short-term (7.2 kg) and intermediate-term (8.0 kg) interventions. A significant global effect of lifestyle intervention on fat mass, waist circumference, blood pressure, total cholesterol, LDL-C, triglycerides and fasting insulin was found (p<0.01), without significant effect on HDL-C and fasting blood glucose. Conclusions Lifestyle interventions incorporating a PA component can improve weight and various cardiometabolic risk factors in class II

  9. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease.

    PubMed

    Zenz, Rainer; Eferl, Robert; Scheinecker, Clemens; Redlich, Kurt; Smolen, Josef; Schonthaler, Helia B; Kenner, Lukas; Tschachler, Erwin; Wagner, Erwin F

    2008-01-01

    Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.

  10. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGES

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  11. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  12. Functional School Activities I. Functional Programming for People with Autism: A Series.

    ERIC Educational Resources Information Center

    Dalrymple, Nancy; Porco, Barbara

    The educational program of a student with autism most easily and beneficially begins with manipulation of objects. Short periods of time should be allotted to each activity to hold attention and ensure success. Partial participation and an individualized reinforcement schedule are important elements in the instructional design. Assistance in…

  13. Function Follows Form: Activation of Shape and Function Features during Object Identification

    ERIC Educational Resources Information Center

    Yee, Eiling; Huffstetler, Stacy; Thompson-Schill, Sharon L.

    2011-01-01

    Most theories of semantic memory characterize knowledge of a given object as comprising a set of semantic features. But how does conceptual activation of these features proceed during object identification? We present the results of a pair of experiments that demonstrate that object recognition is a dynamically unfolding process in which function…

  14. The associations of objectively measured physical activity and sedentary time with cognitive functions in school-aged children.

    PubMed

    Syväoja, Heidi J; Tammelin, Tuija H; Ahonen, Timo; Kankaanpää, Anna; Kantomaa, Marko T

    2014-01-01

    Low levels of physical activity among children have raised concerns over the effects of a physically inactive lifestyle, not only on physical health but also on cognitive prerequisites of learning. This study examined how objectively measured and self-reported physical activity and sedentary behavior are associated with cognitive functions in school-aged children. The study population consisted of 224 children from five schools in the Jyväskylä school district in Finland (mean age 12.2 years; 56% girls), who participated in the study in the spring of 2011. Physical activity and sedentary time were measured objectively for seven consecutive days using the ActiGraph GT1M/GT3X accelerometer. Self-reported moderate to vigorous physical activity (MVPA) and screen time were evaluated with the questions used in the "WHO Health Behavior in School-aged Children" study. Cognitive functions including visual memory, executive functions and attention were evaluated with a computerized Cambridge Neuropsychological Test Automated Battery by using five different tests. Structural equation modeling was applied to examine how objectively measured and self-reported MVPA and sedentary behavior were associated with cognitive functions. High levels of objectively measured MVPA were associated with good performance in the reaction time test. High levels of objectively measured sedentary time were associated with good performance in the sustained attention test. Objectively measured MVPA and sedentary time were not associated with other measures of cognitive functions. High amount of self-reported computer/video game play was associated with weaker performance in working memory test, whereas high amount of computer use was associated with weaker performance in test measuring shifting and flexibility of attention. Self-reported physical activity and total screen time were not associated with any measures of cognitive functions. The results of the present study propose that physical

  15. The Associations of Objectively Measured Physical Activity and Sedentary Time with Cognitive Functions in School-Aged Children

    PubMed Central

    Syväoja, Heidi J.; Tammelin, Tuija H.; Ahonen, Timo; Kankaanpää, Anna; Kantomaa, Marko T.

    2014-01-01

    Low levels of physical activity among children have raised concerns over the effects of a physically inactive lifestyle, not only on physical health but also on cognitive prerequisites of learning. This study examined how objectively measured and self-reported physical activity and sedentary behavior are associated with cognitive functions in school-aged children. The study population consisted of 224 children from five schools in the Jyväskylä school district in Finland (mean age 12.2 years; 56% girls), who participated in the study in the spring of 2011. Physical activity and sedentary time were measured objectively for seven consecutive days using the ActiGraph GT1M/GT3X accelerometer. Self-reported moderate to vigorous physical activity (MVPA) and screen time were evaluated with the questions used in the “WHO Health Behavior in School-aged Children” study. Cognitive functions including visual memory, executive functions and attention were evaluated with a computerized Cambridge Neuropsychological Test Automated Battery by using five different tests. Structural equation modeling was applied to examine how objectively measured and self-reported MVPA and sedentary behavior were associated with cognitive functions. High levels of objectively measured MVPA were associated with good performance in the reaction time test. High levels of objectively measured sedentary time were associated with good performance in the sustained attention test. Objectively measured MVPA and sedentary time were not associated with other measures of cognitive functions. High amount of self-reported computer/video game play was associated with weaker performance in working memory test, whereas high amount of computer use was associated with weaker performance in test measuring shifting and flexibility of attention. Self-reported physical activity and total screen time were not associated with any measures of cognitive functions. The results of the present study propose that physical

  16. Seed dormancy breaking diterpenoids, including novel brassicicenes J and K, from fungus Alternaria brassicicola, and their necrotic/apoptotic activities in HL-60 cells.

    PubMed

    Kenmoku, Hiromichi; Takeue, Sayaka; Oogushi, Megumi; Yagi, Yasuyuki; Sassa, Takeshi; Toyota, Masao; Asakawa, Yoshinori

    2014-03-01

    To find new metabolites similar to cotylenins and fusicoccins from the fungus Alternaria brassicicola, screening tests were carried out using the lettuce seed dormancy breaking assay. Activity-guided fractionation of the EtOAc extract from the culture using the assay afforded the isolation of two novel fusicoccane diterpenoids named brassicicenes J (1) and K (2), along with three known brassicicenes A (3), B (4), and F (5). Their structures were elucidated from extensive NMR spectral data and by comparison of these with those reported in the literature. Brassicicenes (1-5) exhibited weak to moderate seed dormancy breaking activities against lettuce seeds in the presence of abscisic acid. In addition, the necrotic/apoptotic activities of the brassicicenes (1-5), fusicoccin A (6) and cotylenin A (7) were evaluated by determining their cytotoxicity, cell viability and caspase-3/7 activation on the HL-60 cell line. Brassicicene K (2) exhibited similar cytostatic profiles to that of cotylenin A (7), and brassicicenes J (1), A (3), B (4), and F (5) exhibited necrotic activity. This is the first report of the seed dormancy breaking activity of brassicicenes in plants, and of necrotic/apoptotic activity in mammalian cells. PMID:24689212

  17. Employment activities and experiences of adults with high-functioning autism and Asperger’s Disorder.

    PubMed

    Baldwin, Susanna; Costley, Debra; Warren, Anthony

    2014-10-01

    There is limited large-scale empirical research into the working lives of adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on data from a national survey, this report describes the employment activities and experiences of 130 adults with Asperger's Disorder (AD) and high functioning autism (HFA) in Australia. Outcome measures include current occupation; occupational skill level and alignment with educational attainment; type of job contract; hours of work; support received to find work; support received in the workplace; and positive and negative experiences of employment. The findings confirm and expand upon existing evidence that adults with AD and HFA, despite their capacity and willingness to work, face significant disadvantages in the labour market and a lack of understanding and support in employment settings.

  18. Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glucosamine-Functionalized Star Polymers.

    PubMed

    Wong, Edgar H H; Khin, Mya Mya; Ravikumar, Vikashini; Si, Zhangyong; Rice, Scott A; Chan-Park, Mary B

    2016-03-14

    The development of novel reagents and antibiotics for combating multidrug resistance bacteria has received significant attention in recent years. In this study, new antimicrobial star polymers (14-26 nm in diameter) that consist of mixtures of polylysine and glycopolymer arms were developed and were shown to possess antimicrobial efficacy toward Gram positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (with MIC values as low as 16 μg mL(-1)) while being non-hemolytic (HC50 > 10,000 μg mL(-1)) and exhibit excellent mammalian cell biocompatibility. Structure function analysis indicated that the antimicrobial activity and mammalian cell biocompatibility of the star nanoparticles could be optimized by modifying the molar ratio of polylysine to glycopolymers arms. The technology described herein thus represents an innovative approach that could be used to fight deadly infectious diseases.

  19. Highly active antiretroviral therapy-related mechanisms of endothelial and platelet function alterations.

    PubMed

    Gresele, Paolo; Falcinelli, Emanuela; Momi, Stefania; Francisci, Daniela; Baldelli, Franco

    2014-01-01

    Highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV) infection into a chronic condition, which has allowed the infected population to age and become prone to chronic degenerative diseases common to the general population, including atherosclerotic cardiovascular disease, and coronary artery disease (CAD). Possible causative mechanisms of HIV-associated CAD are related to classic cardiovascular risk factors, such as dyslipidemia, insulin resistance, and fat redistribution, which may be due to either HIV infection or to HAART-associated toxicity. However, other mechanisms are emerging as crucial for the cardiovascular complication of HIV and HAART. This article analyzes the effects of HIV and HAART on endothelial function, endothelium-leukocyte interactions, and platelets as possible mechanisms of enhanced cardiovascular risk.

  20. Constitutively Active Mitogen-Activated Protein Kinase Versions Reveal Functions of Arabidopsis MPK4 in Pathogen Defense Signaling[C][W

    PubMed Central

    Berriri, Souha; Garcia, Ana Victoria; dit Frey, Nicolas Frei; Rozhon, Wilfried; Pateyron, Stéphanie; Leonhardt, Nathalie; Montillet, Jean-Luc; Leung, Jeffrey; Hirt, Heribert; Colcombet, Jean

    2012-01-01

    Plant mitogen-activated protein kinases (MAPKs) are involved in important processes, including stress signaling and development. In a functional yeast screen, we identified mutations that render Arabidopsis thaliana MAPKs constitutively active (CA). Importantly, CA-MAPKs maintain their specificity toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4 (MPK4) function in plant immunity was investigated. In agreement with the phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced salicylic acid accumulation and disease resistance. MPK4 activity was found to negatively regulate pathogen-associated molecular pattern-induced reactive oxygen species production but had no impact on callose deposition, indicating that CA-MPK4 allows discriminating between processes regulated by MPK4 activity from processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also found to compromise effector-triggered immunity conditioned by the Toll Interleukin-1 Receptor–nucleotide binding (NB)–Leu-rich repeat (LRR) receptors RPS4 and RPP4 but not by the coiled coil–NB-LRR receptors RPM1 and RPS2. Overall, these data reveal important insights on how MPK4 regulates plant defenses and establishes that CA-MAPKs offer a powerful tool to analyze the function of plant MAPK pathways. PMID:23115249

  1. Brain activation during semantic judgment of Chinese sentences: A functional MRI study.

    PubMed

    Mo, Lei; Liu, Ho-Ling; Jin, Hua; Yang, Ya-Ling

    2005-04-01

    A functional magnetic resonance imaging (fMRI) study was conducted to investigate whether the anatomic substrates of semantic memory may reflect categorical organization and to determine whether the left middle frontal gyrus (Brodmann area [BA] 9) plays a role in Chinese semantic judgment. Unlike previous studies using a word-retrieval task (e.g., word generation, naming, and word categorization), we used a typical task of semantic knowledge retrieval in cognitive psychology in which subjects were asked to determine whether a sentence describing an attribute of living things or nonliving things was true or not. The experimental conditions evoked extensive activation over several regions of the brain including a very strong activation in the left middle frontal region (BA9 and BA46). Our data show that there is no unique activation associated with living or nonliving things at the statistical threshold used in our study. The results imply that human semantic system is undifferentiated by category at the neural level. Our findings also corroborate and extend the claim that the left middle frontal gyrus plays an important role in reading Chinese at both the sentence and the word level. PMID:15704153

  2. The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

    PubMed Central

    Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

    2013-01-01

    This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

  3. Estimation of protein function using template-based alignment of enzyme active sites

    PubMed Central

    2014-01-01

    Background The accumulation of protein structural data occurs more rapidly than it can be characterized by traditional laboratory means. This has motivated widespread efforts to predict enzyme function computationally. The most useful/accurate strategies employed to date are based on the detection of motifs in novel structures that correspond to a specific function. Functional residues are critical components of predictively useful motifs. We have implemented a novel method, to complement current approaches, which detects motifs solely on the basis of distance restraints between catalytic residues. Results ProMOL is a plugin for the PyMOL molecular graphics environment that can be used to create active site motifs for enzymes. A library of 181 active site motifs has been created with ProMOL, based on definitions published in the Catalytic Site Atlas (CSA). Searches with ProMOL produce better than 50% useful Enzyme Commission (EC) class suggestions for level 1 searches in EC classes 1, 4 and 5, and produce some useful results for other classes. 261 additional motifs automatically translated from Jonathan Barker’s JESS motif set [Bioinformatics 19:1644–1649, 2003] and a set of NMR motifs is under development. Alignments are evaluated by visual superposition, Levenshtein distance and root-mean-square deviation (RMSD) and are reasonably consistent with related search methods. Conclusion The ProMOL plugin for PyMOL provides ready access to template-based local alignments. Recent improvements to ProMOL, including the expanded motif library, RMSD calculations and output selection formatting, have greatly increased the program’s usability and speed, and have improved the way that the results are presented. PMID:24669788

  4. Linking Microbial Enzymatic Activities and Functional Diversity of Soil around Earthworm Burrows and Casts

    PubMed Central

    Lipiec, Jerzy; Frąc, Magdalena; Brzezińska, Małgorzata; Turski, Marcin; Oszust, Karolina

    2016-01-01

    The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system [burrow wall (BW) 0–3 mm, transitional zone (TZ) 3–7 mm, bulk soil (BS) > 20 mm from the BW] and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the BW or casts than in BS a