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Sample records for activities impart important

  1. Can exergames impart health messages? Game play, framing, and drivers of physical activity among children.

    PubMed

    Lwin, May O; Malik, Shelly

    2014-01-01

    This study examines the effectiveness of incorporating exergaming into physical education lessons as a platform for imparting health education messages and influencing children's beliefs about and attitudes toward physical activity. The authors launched a 6-week intervention program using Nintendo Wii games coupled with protection motivation theory-based health messaging among 5th-grade school children in Singapore. Results indicated that when children who were exposed to threat-framed messages played Wii exergames during physical education lessons, they reported more positive physical activity attitude, self-efficacy, and perceived behavioral control than did those who underwent regular physical education lessons and were exposed to the same message. In addition, among children playing Wii, the threat and coping frames had similar effects on the degree of message influence on physical activity attitudes and beliefs. The implications for schools, parents, and health policy are discussed.

  2. Imparting Catalytic Activity to a Covalent Organic Framework Material by Nanoparticle Encapsulation.

    PubMed

    Shi, Xiaofei; Yao, Youjin; Xu, Yulong; Liu, Kun; Zhu, Guangshan; Chi, Lifeng; Lu, Guang

    2017-03-01

    Integrating covalent organic frameworks (COFs) with other functional materials is a useful route to enhancing their performances and extending their applications. We report herein a simple encapsulation method for incorporating catalytically active Au nanoparticles with different sizes, shapes, and contents in a two-dimensional (2D) COF material constructed by condensing 1,3,5-tris(4-aminophenyl)benzene (TAPB) with 2,5-dimethoxyterephthaldehyde (DMTP). The encapsulation is assisted by the surface functionalization of Au nanoparticles with polyvinylpyrrolidone (PVP) and follows a mechanism based on the adsorption of nanoparticles onto surfaces of the initially formed polymeric precursor of COF. The incorporation of nanoparticles does not alter obviously the crystallinity, thermal stability, and pore structures of the framework matrices. The obtained COF composites with embedded but accessible Au nanoparticles possess large surface areas and highly open mesopores and display recyclable catalytic performance for reduction of 4-nitrophenol, which cannot be catalyzed by the pure COF material, with activities relevant to contents and geometric structures of the incorporated nanoparticles.

  3. A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2.

    PubMed

    Strege, Peter R; Bernard, Cheryl E; Mazzone, Amelia; Linden, David R; Beyder, Arthur; Gibbons, Simon J; Farrugia, Gianrico

    2015-11-01

    Anoctamin 1 (Ano1; TMEM16A) is a Ca(2+)-activated Cl(-) channel (CACC) expressed in interstitial cells of Cajal. The mechanisms by which Ca(2+) regulates Ano1 are incompletely understood. In the gastrointestinal tract, Ano1 is required for normal slow wave activity and is involved in regulating cell proliferation. Splice variants of Ano1 have varying electrophysiological properties and altered expression in disease states. Recently, we identified a transcript for human Ano1 containing a novel exon-"exon 0" upstream of and in frame with exon 1. The electrophysiological properties of this longer Ano1 isoform are unknown. Our aim was to determine the functional contribution of the newly identified exon to the Ca(2+) sensitivity and electrophysiological properties of Ano1. Constructs with [Ano1(+0)] or without [Ano1(-0)] the newly identified exon were transfected into human embryonic kidney-293 cells. Voltage-clamp electrophysiology was used to determine voltage- and time-dependent parameters of whole cell Cl(-) currents between isoforms with varying concentrations of intracellular Ca(2+), extracellular anions, or Cl(-) channel inhibitors. We found that exon 0 did not change voltage sensitivity and had no impact on the relative permeability of Ano1 to most anions. Ano1(+0) exhibited greater changes in current density but lesser changes in kinetics than Ano1(-0) in response to varying intracellular Ca(2+). The CACC inhibitor niflumic acid inhibited current with greater efficacy and higher potency against Ano1(+0) compared with Ano1(-0). Likewise, the Ano1 inhibitor T16Ainh-A01 reduced Ano1(+0) more than Ano1(-0). In conclusion, human Ano1 containing exon 0 imparts its Cl(-) current with greater sensitivity to intracellular Ca(2+) and CACC inhibitors.

  4. A novel exon in the human Ca2+-activated Cl− channel Ano1 imparts greater sensitivity to intracellular Ca2+

    PubMed Central

    Strege, Peter R.; Bernard, Cheryl E.; Mazzone, Amelia; Linden, David R.; Beyder, Arthur; Gibbons, Simon J.

    2015-01-01

    Anoctamin 1 (Ano1; TMEM16A) is a Ca2+-activated Cl− channel (CACC) expressed in interstitial cells of Cajal. The mechanisms by which Ca2+ regulates Ano1 are incompletely understood. In the gastrointestinal tract, Ano1 is required for normal slow wave activity and is involved in regulating cell proliferation. Splice variants of Ano1 have varying electrophysiological properties and altered expression in disease states. Recently, we identified a transcript for human Ano1 containing a novel exon-“exon 0” upstream of and in frame with exon 1. The electrophysiological properties of this longer Ano1 isoform are unknown. Our aim was to determine the functional contribution of the newly identified exon to the Ca2+ sensitivity and electrophysiological properties of Ano1. Constructs with [Ano1(+0)] or without [Ano1(−0)] the newly identified exon were transfected into human embryonic kidney-293 cells. Voltage-clamp electrophysiology was used to determine voltage- and time-dependent parameters of whole cell Cl− currents between isoforms with varying concentrations of intracellular Ca2+, extracellular anions, or Cl− channel inhibitors. We found that exon 0 did not change voltage sensitivity and had no impact on the relative permeability of Ano1 to most anions. Ano1(+0) exhibited greater changes in current density but lesser changes in kinetics than Ano1(−0) in response to varying intracellular Ca2+. The CACC inhibitor niflumic acid inhibited current with greater efficacy and higher potency against Ano1(+0) compared with Ano1(−0). Likewise, the Ano1 inhibitor T16Ainh-A01 reduced Ano1(+0) more than Ano1(−0). In conclusion, human Ano1 containing exon 0 imparts its Cl− current with greater sensitivity to intracellular Ca2+ and CACC inhibitors. PMID:26359375

  5. Sesamin imparts neuroprotection against intrastriatal 6-hydroxydopamine toxicity by inhibition of astroglial activation, apoptosis, and oxidative stress.

    PubMed

    Baluchnejadmojarad, Tourandokht; Mansouri, Monireh; Ghalami, Jamileh; Mokhtari, Zahra; Roghani, Mehrdad

    2017-04-01

    Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry. These findings reveal the reversal effect of sesamin in 6-OHDA model of PD via attenuation of apoptosis, astrogliosis, oxidative stress, and down-regulation of α-synuclein.

  6. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

    SciTech Connect

    Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

    2012-09-01

    MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

  7. Preparation of silver nano-particles immobilized onto chitin nano-crystals and their application to cellulose paper for imparting antimicrobial activity.

    PubMed

    Li, Zhihan; Zhang, Ming; Cheng, Dong; Yang, Rendang

    2016-10-20

    Immobilized silver nano-particles (Ag NPs) possess excellent antimicrobial properties due to their unique surface characteristics. In this paper, immobilized silver nano-particles were synthesized in the presence of chitin nano-crystals (CNC) based on the Tollens mechanism (reduction of silver ion by aldehydes in the chitosan oligosaccharides (COS)) under microwave-assisted conditions. The prepared Ag NPs-loaded CNC nano-composites were then applied onto the paper surface via coating for the preparation of antibacterial paper. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) results confirmed that the Ag NPs were immobilized onto the CNC. The transmission electron microscope (TEM) and scanning electron microscopy (SEM) results further revealed that the spherical Ag NPs (5-12nm) were well dispersed on the surface of CNC. The coated paper made from the Ag NPs-loaded CNC nano-composites exhibited a high effectiveness of the antibacterial activity against E. coli or S. aureus.

  8. Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation.

    PubMed

    Schmitz, Dietmar; Mellor, Jack; Breustedt, Joerg; Nicoll, Roger A

    2003-10-01

    Hippocampal mossy fiber synapses show an unusual form of long-term potentiation (LTP) that is independent of NMDA receptor activation and is expressed presynaptically. Using receptor antagonists, as well as receptor knockout mice, we found that presynaptic kainate receptors facilitate the induction of mossy fiber long-term potentiation (LTP), although they are not required for this form of LTP. Most importantly, these receptors impart an associativity to mossy fiber LTP such that activity in neighboring mossy fiber synapses, or even associational/commissural synapses, influences the threshold for inducing mossy fiber LTP. Such a mechanism greatly increases the computational power of this form of plasticity.

  9. Estimating Torque Imparted on Spacecraft Using Telemetry

    NASA Technical Reports Server (NTRS)

    Lee, Allan Y.; Wang, Eric K.; Macala, Glenn A.

    2013-01-01

    There have been a number of missions with spacecraft flying by planetary moons with atmospheres; there will be future missions with similar flybys. When a spacecraft such as Cassini flies by a moon with an atmosphere, the spacecraft will experience an atmospheric torque. This torque could be used to determine the density of the atmosphere. This is because the relation between the atmospheric torque vector and the atmosphere density could be established analytically using the mass properties of the spacecraft, known drag coefficient of objects in free-molecular flow, and the spacecraft velocity relative to the moon. The density estimated in this way could be used to check results measured by science instruments. Since the proposed methodology could estimate disturbance torque as small as 0.02 N-m, it could also be used to estimate disturbance torque imparted on the spacecraft during high-altitude flybys.

  10. 75 FR 68809 - Agency Information Collection Activities: Importation Bond Structure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... Information Collection Activities: Importation Bond Structure AGENCY: U.S. Customs and Border Protection...: Importation Bond Structure. This is a proposed extension and revision of an information collection that was...: Importation Bond Structure. OMB Number: 1651-0050. Form Numbers: 301 and 5297. Abstract: Bonds are used...

  11. Zonal drifts of irregularities imparted by meridional winds.

    NASA Technical Reports Server (NTRS)

    Waldman, H.; Da Rosa, A. V.

    1973-01-01

    In a uniform ionosphere, meridional winds cause only meridional motions of irregularities. It is shown, however, that, if F-region irregularities are considered in a real ionosphere in which there is a highly conductive E-layer, zonal motions occur. During the day a substantial westward drift takes place, while at night the drift is eastward but smaller, owing to the much smaller E-layer conductivity. Thus, the effect of meridional winds is to impart a net westward drift to small irregularities in the ionization, provided such irregularities persist long enough.

  12. A new approach for imparting durable multifunctional properties to linen-containing fabrics.

    PubMed

    Ibrahim, N A; El-Zairy, E M; Eid, B M; Emam, E; Barkat, S R

    2017-02-10

    This study focused on upgrading the antibacterial activity, UV-protection property, self-cleaning ability and durability to wash of linen and linen/cotton (50/50) blend fabrics to develop multifunctional textile materials without adversely affecting their hydrophilicity. Herein, linen-containing fabrics were first pre-carboxymethylated to create new active sites (-CH2COOH groups) to facilitate subsequent loading of selected active ingredients namely chitosan (Cs), organosilane quaternary ammonium compound (Si-QAC), silver-nanoparticles (Ag-NPs) and titanium oxide nanoparticles (TiO2-NPs) individually and in admixtures. The developed products, especially in case of using mixed active ingredients, exhibit a noticeable improvement in the imparted functional properties regardless of the used substrate. The effectiveness of the imparted functions is determined by type of substrate, its extent of modification, type, concentration and degree of fixation of the used active ingredient onto the pre-modified substrate. Functionalized samples loaded with mixed active ingredients demonstrated a high durability to wash even after 15 washing cycles.

  13. Seasonal Pacing - Match Importance Affects Activity in Professional Soccer.

    PubMed

    Link, Daniel; de Lorenzo, Michael F

    2016-01-01

    This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1-6) and at the end of a season (round 29-34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing.

  14. Seasonal Pacing - Match Importance Affects Activity in Professional Soccer

    PubMed Central

    Link, Daniel; de Lorenzo, Michael F.

    2016-01-01

    This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1–6) and at the end of a season (round 29–34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing. PMID:27281051

  15. Imparting amphiphobicity on single-crystalline porous materials.

    PubMed

    Sun, Qi; He, Hongming; Gao, Wen-Yang; Aguila, Briana; Wojtas, Lukasz; Dai, Zhifeng; Li, Jixue; Chen, Yu-Sheng; Xiao, Feng-Shou; Ma, Shengqian

    2016-10-31

    The sophisticated control of surface wettability for target-specific applications has attracted widespread interest for use in a plethora of applications. Despite the recent advances in modification of non-porous materials, surface wettability control of porous materials, particularly single crystalline, remains undeveloped. Here we contribute a general method to impart amphiphobicity on single-crystalline porous materials as demonstrated by chemically coating the exterior of metal-organic framework (MOF) crystals with an amphiphobic surface. As amphiphobic porous materials, the resultant MOF crystals exhibit both superhydrophobicity and oleophobicity in addition to retaining high crystallinity and intact porosity. The chemical shielding effect resulting from the amphiphobicity of the MOFs is illustrated by their performances in water/organic vapour adsorption, as well as long-term ultrastability under highly humidified CO2 environments and exceptional chemical stability in acid/base aqueous solutions. Our work thereby pioneers a perspective to protect crystalline porous materials under various chemical environments for numerous applications.

  16. A facile method for imparting superoleophobicity to polymer substrates

    NASA Astrophysics Data System (ADS)

    Ren, Guina; Zhang, Zhaozhu; Zhu, Xiaotao; Ge, Bo; Wang, Kun; Xu, Xianghui; Men, Xuehu; Zhou, Xiaoyan

    2014-03-01

    A new method was presented to impart polymer substrate with superoleophobic properties. Aluminum/polymer composite was created by a hot-pressing process, and rough surface textures needed to establish superoleophobicity were created by HCl etching and boiling water treatment. After surface fluorination, the surface became super-repellent towards water and several organic liquids, such as hexadecane. The effect of geometrical structure on hydrophobicity and oleophobicity was investigated, and the result showed that the synergistic action of microterraces and nanoflakes played a key role in establishing oleophobicity. A waterfall/jet test demonstrated that the obtained surface can keep its superoleophobicity after a long time exposure to water. Moreover, the obtained surface did not lose the superoleophobicity after placing it under cold condition for 7 days.

  17. Imparting amphiphobicity on single-crystalline porous materials

    NASA Astrophysics Data System (ADS)

    Sun, Qi; He, Hongming; Gao, Wen-Yang; Aguila, Briana; Wojtas, Lukasz; Dai, Zhifeng; Li, Jixue; Chen, Yu-Sheng; Xiao, Feng-Shou; Ma, Shengqian

    2016-10-01

    The sophisticated control of surface wettability for target-specific applications has attracted widespread interest for use in a plethora of applications. Despite the recent advances in modification of non-porous materials, surface wettability control of porous materials, particularly single crystalline, remains undeveloped. Here we contribute a general method to impart amphiphobicity on single-crystalline porous materials as demonstrated by chemically coating the exterior of metal-organic framework (MOF) crystals with an amphiphobic surface. As amphiphobic porous materials, the resultant MOF crystals exhibit both superhydrophobicity and oleophobicity in addition to retaining high crystallinity and intact porosity. The chemical shielding effect resulting from the amphiphobicity of the MOFs is illustrated by their performances in water/organic vapour adsorption, as well as long-term ultrastability under highly humidified CO2 environments and exceptional chemical stability in acid/base aqueous solutions. Our work thereby pioneers a perspective to protect crystalline porous materials under various chemical environments for numerous applications.

  18. Method for imparting selectivity to polymeric gel systems

    SciTech Connect

    Hoskin, D.H.; Sifferman, T.R.

    1992-10-20

    This patent describes a method for imparting selectivity to an in-situ gel-forming composition for placement within a subterranean oil-bearing formation having relatively high permeability zones and relatively low permeability zones. It comprises: preparing an aqueous-based mixture comprising: a first stage gel-forming composition; at least one second stage in-situ gel-forming composition comprising a water-dispersible polymer and a crosslinking agent for the water-dispersible polymer in an amount effective to form a stable gel; and gelling the first stage gel-forming composition exsitu by reacting the Xanthomonas campestris NCIB 1185 heteropolysaccharide with the crosslinking agent for the heteropolysaccharide; wherein the mixture exhibits greater selectivity than would a like mixture in the absence of the first stage selective gel-forming composition.

  19. Identification of Critical Amino Acids within the Nucleoprotein of Tacaribe Virus Important for Anti-interferon Activity*

    PubMed Central

    Harmon, Brooke; Kozina, Carol; Maar, Dianna; Carpenter, Timothy S.; Branda, Catherine S.; Negrete, Oscar A.; Carson, Bryan D.

    2013-01-01

    The arenavirus nucleoprotein (NP) can suppress induction of type I interferon (IFN). This anti-IFN activity is thought to be shared by all arenaviruses with the exception of Tacaribe virus (TCRV). To identify the TCRV NP amino acid residues that prevent its IFN-countering ability, we created a series of NP chimeras between residues of TCRV NP and Pichinde virus (PICV) NP, an arenavirus NP with potent anti-IFN function. Chimera NP analysis revealed that a minimal four amino acid stretch derived from PICV NP could impart efficient anti-IFN activity to TCRV NP. Strikingly, the TCRV NP gene cloned and sequenced from viral stocks obtained through National Institutes of Health Biodefense and Emerging Infections (BEI) resources deviated from the reference sequence at this particular four-amino acid region, GPPT (GenBank KC329849) versus DLQL (GenBank NC004293), respectively at residues 389–392. When efficiently expressed in cells through codon-optimization, TCRV NP containing the GPPT residues rescued the antagonistic IFN function. Consistent with cell expression results, TCRV infection did not stimulate an IFNβ response early in infection in multiple cells types (e.g. A549, P388D1), and IRF-3 was not translocated to the nucleus in TCRV-infected A549 cells. Collectively, these data suggest that certain TCRV strain variants contain the important NP amino acids necessary for anti-IFN activity. PMID:23382389

  20. Imparting amphiphobicity on single-crystalline porous materials

    PubMed Central

    Sun, Qi; He, Hongming; Gao, Wen-Yang; Aguila, Briana; Wojtas, Lukasz; Dai, Zhifeng; Li, Jixue; Chen, Yu-Sheng; Xiao, Feng-Shou; Ma, Shengqian

    2016-01-01

    The sophisticated control of surface wettability for target-specific applications has attracted widespread interest for use in a plethora of applications. Despite the recent advances in modification of non-porous materials, surface wettability control of porous materials, particularly single crystalline, remains undeveloped. Here we contribute a general method to impart amphiphobicity on single-crystalline porous materials as demonstrated by chemically coating the exterior of metal-organic framework (MOF) crystals with an amphiphobic surface. As amphiphobic porous materials, the resultant MOF crystals exhibit both superhydrophobicity and oleophobicity in addition to retaining high crystallinity and intact porosity. The chemical shielding effect resulting from the amphiphobicity of the MOFs is illustrated by their performances in water/organic vapour adsorption, as well as long-term ultrastability under highly humidified CO2 environments and exceptional chemical stability in acid/base aqueous solutions. Our work thereby pioneers a perspective to protect crystalline porous materials under various chemical environments for numerous applications. PMID:27796363

  1. Parent participation plays an important part in promoting physical activity

    PubMed Central

    Lindqvist, Anna-Karin; Kostenius, Catrine; Gard, Gunvor; Rutberg, Stina

    2015-01-01

    Although physical activity (PA) is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents’ PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents’ experiences of being a part of their adolescents’ empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents’, but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based. PMID:26282870

  2. Parent participation plays an important part in promoting physical activity.

    PubMed

    Lindqvist, Anna-Karin; Kostenius, Catrine; Gard, Gunvor; Rutberg, Stina

    2015-01-01

    Although physical activity (PA) is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents' PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents' experiences of being a part of their adolescents' empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents', but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based.

  3. Stellar Activity and CMEs: Important Factors of Planetary Evolution

    NASA Astrophysics Data System (ADS)

    Khodachenko, Maxim L.

    CME activity of the Sun is known to be an important impacting factor for the magnetospheres, atmospheres, and surfaces of solar system planets. Following an idea of a solar-stellar analogy, CME phenomena are expected on other stars as well. The main planetary impact factors of the stellar CMEs include the associated interplanetary shocks, plasma density and velocity disturbances, energetic particles accelerated in the shock regions, as well as distortions of the magnetic field direction and modulus. All these factors should be properly taken into account during the study of evolutionary processes on exoplanets and their atmospheric and plasma environments. The planetary impact of the stellar CME activity may vary depending on stellar age, stellar spectral type and the orbital distance of a planet. Because of the relatively short range of propagation of the majority of CMEs, they affect most strongly the magnetospheres and atmospheres of close-orbit ( < 0.1 AU) exoplanets. In this chapter we discuss an issue of the stellar CME activity in the context of several actual problems of modern exoplanetology, including planetary atmosphere mass loss, planet survival at close orbits, and definition of a criterion for habitability.

  4. LOV-based optogenetic devices: light-driven modules to impart photoregulated control of cellular signaling

    PubMed Central

    Pudasaini, Ashutosh; El-Arab, Kaley K.; Zoltowski, Brian D.

    2015-01-01

    The Light-Oxygen-Voltage domain family of proteins is widespread in biology where they impart sensory responses to signal transduction domains. The small, light responsive LOV modules offer a novel platform for the construction of optogenetic tools. Currently, the design and implementation of these devices is partially hindered by a lack of understanding of how light drives allosteric changes in protein conformation to activate diverse signal transduction domains. Further, divergent photocycle properties amongst LOV family members complicate construction of highly sensitive devices with fast on/off kinetics. In the present review we discuss the history of LOV domain research with primary emphasis on tuning LOV domain chemistry and signal transduction to allow for improved optogenetic tools. PMID:25988185

  5. Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth.

    PubMed

    Sharma, Ashwani; Aher, Amol; Dynes, Nicola J; Frey, Daniel; Katrukha, Eugene A; Jaussi, Rolf; Grigoriev, Ilya; Croisier, Marie; Kammerer, Richard A; Akhmanova, Anna; Gönczy, Pierre; Steinmetz, Michel O

    2016-05-23

    Centrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can interact with tubulin or microtubules, but how they ensure the exceptionally slow growth of centriolar microtubules has remained mysterious. Here, we bring together crystallographic, biophysical, and reconstitution assays to demonstrate that the human centriolar protein CPAP (SAS-4 in worms and flies) binds and "caps" microtubule plus ends by associating with a site of β-tubulin engaged in longitudinal tubulin-tubulin interactions. Strikingly, we uncover that CPAP activity dampens microtubule growth and stabilizes microtubules by inhibiting catastrophes and promoting rescues. We further establish that the capping function of CPAP is important to limit growth of centriolar microtubules in cells. Our results suggest that CPAP acts as a molecular lid that ensures slow assembly of centriolar microtubules and, thereby, contributes to organelle length control.

  6. Active Learning: The Importance of Developing a Comprehensive Measure

    ERIC Educational Resources Information Center

    Carr, Rodney; Palmer, Stuart; Hagel, Pauline

    2015-01-01

    This article reports on an investigation into the validity of a widely used scale for measuring the extent to which higher education students employ active learning strategies. The scale is the active learning scale in the Australasian Survey of Student Engagement. This scale is based on the Active and Collaborative Learning scale of the National…

  7. 75 FR 50772 - Agency Information Collection Activities: Importation Bond Structure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-17

    ... Structure AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ] ACTION: 60-Day... concerning the: Importation Bond Structure. This request for comment is being made pursuant to the Paperwork...: Title: Importation Bond Structure. OMB Number: 1651-0050. Form Numbers: 301 and 5297. Abstract:...

  8. Physical activity: health outcomes and importance for public health policy.

    PubMed

    Haskell, William L; Blair, Steven N; Hill, James O

    2009-10-01

    This manuscript presents a brief summary of the substantial data supporting an inverse relationship between the amount of habitual physical activity performed and a variety of negative health outcomes throughout the lifespan. It points out that despite these data a large segment of the US population remain insufficiently active resulting in a high population attributable risk for chronic disease due to inactivity. The accumulated data support the need for more comprehensive health promoting physical activity policies and programs, especially for the economically and socially disadvantaged and medically underserved.

  9. 78 FR 75576 - Agency Information Collection Activities: Importation Bond Structure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... Structure AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland Security. ACTION: 60-day... Importation Bond Structure. This request for comment is being made pursuant to the Paperwork Reduction Act of... Structure. OMB Number: 1651-0050. Form Number: CBP Forms 301 and 5297. Abstract: Bonds are used to...

  10. Compounds active against cell walls of medically important fungi.

    PubMed Central

    Hector, R F

    1993-01-01

    A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development. PMID:8457977

  11. Disassembly of micelles to impart donor and acceptor gradation to enhance organic solar cell efficiency.

    PubMed

    Arulkashmir, Arulraj; Krishnamoorthy, Kothandam

    2016-02-28

    A transparent, conducting and low surface energy surface was prepared by disassembly of anionic micelles, which altered the orientation of the donor polymer and imparted gradation between the donor and acceptor. This configuration increased the solar cell device efficiency.

  12. The active liquid Earth - importance of temporal and spatial variability

    NASA Astrophysics Data System (ADS)

    Arheimer, Berit

    2016-04-01

    The Planet Earth is indeed liquid and active - 71 percent of its surface is water-covered and this water never rests. Thanks to the water cycle, our planet's water supply is constantly moving from one place to another and from one form to another. Only 2.5% of the water is freshwater and it exists in the air as water vapor; it hits the ground as rain and snow; it flows on the surface from higher to lower altitudes in rivers, lakes, and glaciers; and it flows in the ground in soil, aquifers, and in all living organisms until it reaches the sea. On its way over the Earth's crust, some returns quickly to vapor again, while some is trapped and exposed to many "fill and spill" situations for a long journey. The variability in the water balance is crucial for hydrological understanding and modelling. The water cycle may appear simple, but magnitudes and rates in fluxes are very different from one place to another, resulting from variable drivers such as solar energy, precipitation and gravity in co-evolution with geology, soil, vegetation and fauna. The historical evolution, the temporal fluxes and diversity in space continue to fascinate hydrological scientists. Specific physical processes may be well known, but their boundary conditions, interactions and rate often remain unknown at a specific site and are difficult to monitor in nature. This results in mysterious features where trends in drivers do not match runoff, like the Sahelian Paradox or discharge to the Arctic Ocean. Humans have always interfered with the water cycle and engineering is fundamental for water regulation and re-allocation. Some 80% of the river flow from the northern part of the Earth is affected by fragmentation of the river channels by dams. In water management, there is always a tradeoff between upstream and downstream activities, not only regarding total water quantities but also for temporal patterns and water quality aspects. Sharing a water resource can generate conflicts but geopolitical

  13. Imparting regenerative capacity to limbs by progenitor cell transplantation

    PubMed Central

    Lin, Gufa; Chen, Ying; Slack, Jonathan M.W.

    2012-01-01

    Summary The frog Xenopus can normally regenerate its limbs at early developmental stages but loses the ability during metamorphosis. This behavior provides a potential gain-of-function model for measures that can enhance limb regeneration. Here we show that frog limbs can be caused to form multidigit regenerates after receiving transplants of larval limb progenitor cells. It is necessary to activate Wnt/β -catenin signaling in the cells, and to add Sonic hedgehog, FGF10 and thymosin β4. These factors promote survival and growth of the grafted cells and also provide pattern information. The eventual regenerates are not composed solely of donor tissue; the host cells also make a substantial contribution despite their lack of regeneration-competence. Cells from adult frog legs or from regenerating tadpole tails do not promote limb regeneration, demonstrating the necessity for limb progenitor cells. These findings have obvious implications for the development of a technology to promote limb regeneration in mammals. PMID:23273877

  14. Metabolically Labile Fumarate Esters Impart Kinetic Selectivity to Irreversible Inhibitors.

    PubMed

    Zaro, Balyn W; Whitby, Landon R; Lum, Kenneth M; Cravatt, Benjamin F

    2016-12-14

    Electrophilic small molecules are an important class of chemical probes and drugs that produce biological effects by irreversibly modifying proteins. Examples of electrophilic drugs include covalent kinase inhibitors that are used to treat cancer and the multiple sclerosis drug dimethyl fumarate. Optimized covalent drugs typically inactivate their protein targets rapidly in cells, but ensuing time-dependent, off-target protein modification can erode selectivity and diminish the utility of reactive small molecules as chemical probes and therapeutics. Here, we describe an approach to confer kinetic selectivity to electrophilic drugs. We show that an analogue of the covalent Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib bearing a fumarate ester electrophile is vulnerable to enzymatic metabolism on a time-scale that preserves rapid and sustained BTK inhibition, while thwarting more slowly accumulating off-target reactivity in cell and animal models. These findings demonstrate that metabolically labile electrophilic groups can endow covalent drugs with kinetic selectivity to enable perturbation of proteins and biochemical pathways with greater precision.

  15. Betaine Transport Imparts Osmotolerance on a Strain of Lactobacillus acidophilus

    PubMed Central

    Hutkins, Robert W.; Ellefson, William L.; Kashket, Eva R.

    1987-01-01

    Unlike most Lactobacillus acidophilus strains, a specific strain, L. acidophilus IFO 3532, was found to grow in rich medium containing 1 M sodium acetate, KCl, or NaCl. This strain could also grow with up to 1.8 M NaCl or 3 M nonelectrolytes (fructose, xylose, or sorbitol) added. Thus, this strain was tolerant to osmotic pressures up to 2.8 osM. A search for an intracellular solute which conferred osmoprotection led to the identification of glycine betaine (betaine). Betaine was accumulated to high concentrations in cells growing in MRS medium supplemented with 1 M KCl or NaCl. Uptake of [14C]betaine by L. acidophilus 3532 cells suspended in buffer was stimulated by increasing the medium osmotic pressure with 1 M KCl or NaCl. The accumulated betaine was not metabolized further; transport was relatively specific for betaine and was dependent on an energy source. Other lactobacilli, more osmosensitive than strain 3532, including L. acidophilus strain E4356, L. bulgaricus 8144, and L. delbrueckii 9649, showed lower betaine transport rates in response to an osmotic challenge than L. acidophilus 3532. Experiments with chloramphenicol-treated L. acidophilus 3532 cells indicated that the transport system was not induced but appeared to be activated by an increase in osmotic pressure. PMID:16347448

  16. Machine imparting complex rotary motion for lapping a spherical inner diameter

    DOEpatents

    Carroll, Thomas A.; Yetter, Harold H.

    1986-01-01

    An apparatus for imparting complex rotary motion is used to lap an inner spherical diameter surface of a workpiece. A lapping tool consists of a dome and rod mounted along the dome's vertical axis. The workpiece containing the lapping tool is held in a gimbal which uses power derived from a secondary takeoff means to impart rotary motion about a horizontal axis. The gimbal is rotated about a vertical axis by a take means while mounted at a radially outward position on a rotating arm.

  17. Machine imparting complex rotary motion for lapping a spherical inner diameter

    DOEpatents

    Carroll, T.A.; Yetter, H.H.

    1985-01-30

    An apparatus for imparting complex rotary motion is used to lap an inner spherical diameter surface of a workpiece. A lapping tool consists of a dome and rod mounted along the dome's vertical axis. The workpiece containing the lapping tool is held in a gimbal which uses power derived from a secondary takeoff means to impart rotary motion about a horizontal axis. The gimbal is rotated about a vertical axis by a take means while mounted at a radially outward position on a rotating arm.

  18. Clay and DOPA containing polyelectrolyte multilayer film for imparting anticorrosion properties to galvanized steel.

    PubMed

    Faure, Emilie; Halusiak, Emilie; Farina, Fabrice; Giamblanco, Nicoletta; Motte, Cécile; Poelman, Mireille; Archambeau, Catherine; Van de Weerdt, Cécile; Martial, Joseph; Jérôme, Christine; Duwez, Anne-Sophie; Detrembleur, Christophe

    2012-02-07

    A facile and green approach is developed to impart remarkable protection against corrosion to galvanized steel. A protecting multilayer film is formed by alternating the deposition of a polycation bearing catechol groups, used as corrosion inhibitors, with clay that induces barrier properties. This coating does not affect the esthetical aspect of the surface and does not release any toxic molecules in the environment.

  19. Imparting small vorticity to a Bianchi type-VIh empty spacetime

    NASA Astrophysics Data System (ADS)

    Batakis, Nikos A.

    1981-04-01

    We present and briefly discuss a Bianchi type-VIh empty spacetime. The field equations have been solved after being linearized with respect to a parameter which imparts vorticity to the model. The limit of zero vorticity is an already known solution.

  20. Imparting Barely Visible Impact Damage to a Stitched Composite Large-Scale Pressure Box

    NASA Technical Reports Server (NTRS)

    Lovejoy, Andrew E.; Przekop, Adam

    2016-01-01

    The Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) is a concept that was developed by The Boeing Company to address the complex structural design aspects associated with a pressurized hybrid wing body (HWB) aircraft configuration, which has been a focus of the NASA Environmentally Responsible Aviation Project. The NASA-Boeing structural development for the HWB aircraft culminated in testing of the multi-bay box, which is an 80%-scale representation of the pressurized center-body section. This structure was tested in the NASA Langley Research Center Combined Loads Test System facility. As part of this testing, barely visible impact damage was imparted to the interior and exterior of the test article to demonstrate compliance with a condition representative of the requirements for Category 1 damaged composite structure as defined by the Federal Aviation Regulations. Interior impacts were imparted using an existing spring-loaded impactor, while the exterior impacts were imparted using a newly designed, gravity-driven impactor. This paper describes the impacts to the test article, and the design of the gravitydriven guided-weight impactor. The guided-weight impactor proved to be a very reliable method to impart barely visible impact damage in locations which are not easily accessible for a traditional drop-weight impactor, while at the same time having the capability to be highly configurable for use on other aircraft structures.

  1. 76 FR 40749 - Agency Information Collection Activities: Records and Supporting Data: Importation, Receipt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... of Alcohol, Tobacco, Firearms and Explosives Agency Information Collection Activities: Records and Supporting Data: Importation, Receipt, Storage, and Disposition by Explosives Importers, Manufacturers..., Firearms and Explosives (ATF), will be submitting the following information collection request to...

  2. Using Importance-Performance Analysis to Guide Instructional Design of Experiential Learning Activities

    ERIC Educational Resources Information Center

    Anderson, Sheri; Hsu, Yu-Chang; Kinney, Judy

    2016-01-01

    Designing experiential learning activities requires an instructor to think about what they want the students to learn. Using importance-performance analysis can assist with the instructional design of the activities. This exploratory study used importance-performance analysis in an online introduction to criminology course. There is limited…

  3. Imparting Motion to a Test Object Such as a Motor Vehicle in a Controlled Fashion

    NASA Technical Reports Server (NTRS)

    Southward, Stephen C. (Inventor); Reubush, Chandler (Inventor); Pittman, Bryan (Inventor); Roehrig, Kurt (Inventor); Gerard, Doug (Inventor)

    2014-01-01

    An apparatus imparts motion to a test object such as a motor vehicle in a controlled fashion. A base has mounted on it a linear electromagnetic motor having a first end and a second end, the first end being connected to the base. A pneumatic cylinder and piston combination have a first end and a second end, the first end connected to the base so that the pneumatic cylinder and piston combination is generally parallel with the linear electromagnetic motor. The second ends of the linear electromagnetic motor and pneumatic cylinder and piston combination being commonly linked to a mount for the test object. A control system for the linear electromagnetic motor and pneumatic cylinder and piston combination drives the pneumatic cylinder and piston combination to support a substantial static load of the test object and the linear electromagnetic motor to impart controlled motion to the test object.

  4. Model for radial dependence of frequency distributions for energy imparted in nanometer volumes from HZE particles

    NASA Technical Reports Server (NTRS)

    Cucinotta, F. A.; Nikjoo, H.; Goodhead, D. T.; Decillo, J. F. (Principal Investigator)

    2000-01-01

    This paper develops a deterministic model of frequency distributions for energy imparted (total energy deposition) in small volumes similar to DNA molecules from high-energy ions of interest for space radiation protection and cancer therapy. Frequency distributions for energy imparted are useful for considering radiation quality and for modeling biological damage produced by ionizing radiation. For high-energy ions, secondary electron (delta-ray) tracks originating from a primary ion track make dominant contributions to energy deposition events in small volumes. Our method uses the distribution of electrons produced about an ion's path and incorporates results from Monte Carlo simulation of electron tracks to predict frequency distributions for ions, including their dependence on radial distance. The contribution from primary ion events is treated using an impact parameter formalism of spatially restricted linear energy transfer (LET) and energy-transfer straggling. We validate our model by comparing it directly to results from Monte Carlo simulations for proton and alpha-particle tracks. We show for the first time frequency distributions of energy imparted in DNA structures by several high-energy ions such as cosmic-ray iron ions. Our comparison with results from Monte Carlo simulations at low energies indicates the accuracy of the method.

  5. Simple methods for the estimation of dose distributions, organ doses and energy imparted in paediatric radiology.

    PubMed

    Almén, A; Nilsson, M

    1996-07-01

    The energy imparted and the effective dose can both be used to describe the risk to the patient in diagnostic radiology. Simple methods must be employed to determine these quantities in clinical situations. Methods using measured relative depth-dose distributions are presented and evaluated here. Measurements of depth-dose distributions for x-ray beams were performed with an ionization chamber, a diode and a number of TL dosimeters. The energy imparted was calculated from measurements with both phantoms and patients. The method of calculating the mean absorbed dose to organs was applied to pelvis and lumbar spine examinations. TL dosimeters were found to be an appropriate detector for measuring depth-dose distributions. When calculating the energy imparted the entrance beam area must be accurately known. The mean absorbed dose to organs can be derived from measured relative depth-dose curves if accurate information on entrance beam position and area is available for the particular examination technique used. The advantage of these methods is that the dose distribution is measured for the photon beam used for the examination of the patients.

  6. Design and Use of a Guided Weight Impactor to Impart Barely Visible Impact Damage

    NASA Technical Reports Server (NTRS)

    Lovejoy, Andrew E.; Przekop, Adam

    2016-01-01

    Aircraft structure is required to demonstrate satisfaction of the FAR requirements for Category 1, such as barely visible impact damage (BVID). Typical aircraft structure is impacted using a dropped weight impactor, which can impart BVID to the top surface of the structure. A recent test of a multi-bay box (MBB) composite test article, that represents an 80% scale center section of a hybrid wing body aircraft, required impact to be in a direction other than vertical from above, but still in an direction that is normal to the surface. This requirement eliminated the use of the conventional dropped weight impactor. Therefore, a design study was undertaken to determine the most effective way to efficiently and reliably impact the MBB. The chosen design was a guided weight impactor that is gravity driven. This paper describes the design of the guided weight impactor, and presents the results of its use for imparting BVID to the MBB. The guided weight impactor was seen to be a very reliable method to impart BVID, while at the same time having the capability to be highly configurable for use on other aircraft structure that is impacted at a variety of impact energies and from a variety of directions.

  7. Physical Activity in the Heat: Important Considerations to Keep Your Students Safe

    ERIC Educational Resources Information Center

    Roetert, E. Paul; Richardson, Cheryl L.; Bergeron, Michael F.

    2012-01-01

    Although July and August tend to be the warmest months of the year, the months leading up to summer as well as the months just following summer can also be quite warm or even very hot. In this article, the authors share some important information to help prepare physical educators for overseeing activities in the heat and, just as importantly, to…

  8. Active fault and water loading are important factors in triggering earthquake activity around Aswan Lake

    NASA Astrophysics Data System (ADS)

    Kebeasy, R. M.; Gharib, A. A.

    Aswan Lake started impounding in 1964 and reached the highest water level so far in 1978 with a capacity of 133.8 km 3, thus forming the second largest man-made lake in the world. An earthquake of magnitude 5.3 (Ms) took place on 14 November 1981 along the most active part of the E-W Kalabsha fault beneath the Kalabsha bay (the largest bay of the lake). This earthquake was followed by a tremendous number of smaller events that continue till now. A radio-telemetry network of 13 seismic short period stations and a piezometer network of six wells were established around the northern part of the lake. Epicenters were found to cluster around active faults near the lake. The space-time distribution and the relation of the seismicity with the lake water level fluctuations were studied. Six years after flooding the eastern segment of the Kalabsha fault, strong seismicity began following the main shock of 14 November 1981. It occurred four days after the reservoir had reached its seasonal max level. The effect of the North African drought (1982 to present) is clearly seen in the reservoir water level. As it decreased and left the most active fault segments uncovered, the activity (Gebel Marawa area) decreased sharply. Also, the shallow activity was found to be more sensitive to rapid discharging than to the filling. This study indicates that geology, topography, lineations in seismicity, offsets in the faults, changes in fault trends and focal mechanisms are closely related. No relation was found between earthquake activity and both-ground water table fluctuations and water temperatures measured in wells located around the Kalabsha area.

  9. Alanine-Scanning Mutational Analysis of Durancin GL Reveals Residues Important for Its Antimicrobial Activity.

    PubMed

    Ju, Xingrong; Chen, Xinquan; Du, Lihui; Wu, Xueyou; Liu, Fang; Yuan, Jian

    2015-07-22

    Durancin GL is a novel class IIa bacteriocin with 43 residues produced by Enterococcus durans 41D. This bacteriocin demonstrates narrow inhibition spectrum and potent antimicrobial activity against several Listeria monocytogenes strains, including nisin-resistant L. monocytogenes NR30. A systematic alanine-scanning mutational analysis with site-directed mutagenesis was performed to analyze durancin GL residues important for antimicrobial activity and specificity. Results showed that three mutations lost their antimicrobial activity, ten mutations demonstrated a decreased effect on the activity, and seven mutations exhibited relatively high activity. With regard to inhibitory spectrum, four mutants demonstrated a narrower antimicrobial spectrum than wild-type durancin GL. Another four mutants displayed a broader target cell spectrum and increased potency relative to wild-type durancin GL. These findings broaden our understanding of durancin GL residues important for its antimicrobial activity and contribute to future rational design of variants with increased potency.

  10. Extensive mutagenesis of a transcriptional activation domain identifies single hydrophobic and acidic amino acids important for activation in vivo.

    PubMed Central

    Sainz, M B; Goff, S A; Chandler, V L

    1997-01-01

    C1 is a transcriptional activator of genes encoding biosynthetic enzymes of the maize anthocyanin pigment pathway. C1 has an amino terminus homologous to Myb DNA-binding domains and an acidic carboxyl terminus that is a transcriptional activation domain in maize and yeast cells. To identify amino acids critical for transcriptional activation, an extensive random mutagenesis of the C1 carboxyl terminus was done. The C1 activation domain is remarkably tolerant of amino acid substitutions, as changes at 34 residues had little or no effect on transcriptional activity. These changes include introduction of helix-incompatible amino acids throughout the C1 activation domain and alteration of most single acidic amino acids, suggesting that a previously postulated amphipathic alpha-helix is not required for activation. Substitutions at two positions revealed amino acids important for transcriptional activation. Replacement of leucine 253 with a proline or glutamine resulted in approximately 10% of wild-type transcriptional activation. Leucine 253 is in a region of C1 in which several hydrophobic residues align with residues important for transcriptional activation by the herpes simplex virus VP16 protein. However, changes at all other hydrophobic residues in C1 indicate that none are critical for C1 transcriptional activation. The other important amino acid in C1 is aspartate 262, as a change to valine resulted in only 24% of wild-type transcriptional activation. Comparison of our C1 results with those from VP16 reveal substantial differences in which amino acids are required for transcriptional activation in vivo by these two acidic activation domains. PMID:8972191

  11. Axial force imparted by a conical radiofrequency magneto-plasma thruster

    SciTech Connect

    Charles, C.; Takahashi, K.; Boswell, R. W.

    2012-03-12

    Direct thrust measurements of a low pressure ({approx}0.133 Pa) conical radiofrequency (rf at 13.56 MHz) argon plasma source show a total axial force of about 5 mN for an effective rf power of 650 W and a maximum magnetic field of 0.018 T, of which a measured value of 2.5 mN is imparted by the magnetic nozzle. A simplified model of thrust including contributions from the electron pressure and from the magnetic field pressure is developed. The magnetic nozzle is modelled as a ''physical'' nozzle of increasing cross-sectional area.

  12. An automated technique for estimating patient-specific regional imparted energy and dose in TCM CT exams

    NASA Astrophysics Data System (ADS)

    Sanders, Jeremiah W.; Tian, Xiaoyu; Segars, W. Paul; Boone, John; Samei, Ehsan

    2016-03-01

    Currently computed tomography (CT) dosimetry relies on CT dose index (CTDI) and size specific dose estimates (SSDE). Organ dose is a better metric of radiation burden. However, organ dose estimation requires precise knowledge of organ locations. Regional imparted energy and dose can also be used to quantify radiation burden. Estimating the imparted energy from CT exams is beneficial in that it does not require precise estimates of the organ size or location. This work investigated an automated technique for retrospectively estimating the imparted energy from chest and abdominopelvic tube current modulated (TCM) CT exams. Monte Carlo simulations of chest and abdominopelvic TCM CT examinations across various tube potentials and TCM strengths were performed on 58 adult computational extended cardiac-torso (XCAT) phantoms to develop relationships between scanned mass and imparted energy normalized by dose length product (DLP). An automated algorithm for calculating the scanned patient volume was further developed using an open source mesh generation toolbox. The scanned patient volume was then used to estimate the scanned mass accounting for diverse density within the scan region. The scanned mass and DLP from the exam were used to estimate the imparted energy to the patient using the knowledgebase developed from the Monte Carlo simulations. Patientspecific imparted energy estimates were made from 20 chest and 20 abdominopelvic clinical CT exams. The average imparted energy was 274 +/- 141 mJ and 681 +/- 376 mJ for the chest and abdominopelvic exams, respectively. This method can be used to estimate the regional imparted energy and/or regional dose in chest and abdominopelvic TCM CT exams across clinical operations.

  13. Improving importance estimation in pool-based batch active learning for approximate linear regression.

    PubMed

    Kurihara, Nozomi; Sugiyama, Masashi

    2012-12-01

    Pool-based batch active learning is aimed at choosing training inputs from a 'pool' of test inputs so that the generalization error is minimized. P-ALICE (Pool-based Active Learning using Importance-weighted least-squares learning based on Conditional Expectation of the generalization error) is a state-of-the-art method that can cope with model misspecification by weighting training samples according to the importance (i.e., the ratio of test and training input densities). However, importance estimation in the original P-ALICE is based on the assumption that the number of training samples to gather is small, which is not always true in practice. In this paper, we propose an alternative scheme for importance estimation based on the inclusion probability, and show its validity through numerical experiments.

  14. III. The importance of physical activity and aerobic fitness for cognitive control and memory in children.

    PubMed

    Chaddock-Heyman, Laura; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F

    2014-12-01

    In this chapter, we review literature that examines the association among physical activity, aerobic fitness, cognition, and the brain in elementary school children (ages 7-10 years). Specifically, physical activity and higher levels of aerobic fitness in children have been found to benefit brain structure, brain function, cognition, and school achievement. For example, higher fit children have larger brain volumes in the basal ganglia and hippocampus, which relate to superior performance on tasks of cognitive control and memory, respectively, when compared to their lower fit peers. Higher fit children also show superior brain function during tasks of cognitive control, better scores on tests of academic achievement, and higher performance on a real-world street crossing task, compared to lower fit and less active children. The cross-sectional findings are strengthened by a few randomized, controlled trials, which demonstrate that children randomly assigned to a physical activity intervention group show greater brain and cognitive benefits compared to a control group. Because these findings suggest that the developing brain is plastic and sensitive to lifestyle factors, we also discuss typical structural and functional brain maturation in children to provide context in which to interpret the effects of physical activity and aerobic fitness on the developing brain. This research is important because children are becoming increasingly sedentary, physically inactive, and unfit. An important goal of this review is to emphasize the importance of physical activity and aerobic fitness for the cognitive and brain health of today's youth.

  15. Imparting functionality to biocatalysts via embedding enzymes into nanoporous materials by a de novo approach: size-selective sheltering of catalase in metal-organic framework microcrystals.

    PubMed

    Shieh, Fa-Kuen; Wang, Shao-Chun; Yen, Chia-I; Wu, Chang-Cheng; Dutta, Saikat; Chou, Lien-Yang; Morabito, Joseph V; Hu, Pan; Hsu, Ming-Hua; Wu, Kevin C-W; Tsung, Chia-Kuang

    2015-04-08

    We develop a new concept to impart new functions to biocatalysts by combining enzymes and metal-organic frameworks (MOFs). The proof-of-concept design is demonstrated by embedding catalase molecules into uniformly sized ZIF-90 crystals via a de novo approach. We have carried out electron microscopy, X-ray diffraction, nitrogen sorption, electrophoresis, thermogravimetric analysis, and confocal microscopy to confirm that the ~10 nm catalase molecules are embedded in 2 μm single-crystalline ZIF-90 crystals with ~5 wt % loading. Because catalase is immobilized and sheltered by the ZIF-90 crystals, the composites show activity in hydrogen peroxide degradation even in the presence of protease proteinase K.

  16. How My Daughter Taught Me to Teach: The Importance of Active Communication

    ERIC Educational Resources Information Center

    Hunt-Gierut, Deborah

    2011-01-01

    In this article, the author shares how her daughter, who was diagnosed with a profound hearing loss when she was a year old, taught her to teach, and demonstrates the importance of active communication. Teaching her daughter English as her second language has posed many challenges, but has also revealed successful strategies that the author has…

  17. 77 FR 19681 - Agency Information Collection Activities: Importers of Merchandise Subject to Actual Use Provisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Importers of Merchandise Subject to Actual Use Provisions AGENCY: U.S. Customs and Border Protection, Department of... collection. SUMMARY: U.S. Customs and Border Protection (CBP) of the Department of Homeland Security will...

  18. 77 FR 55486 - Agency Information Collection Activities: Importer ID Input Record

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Importer ID Input Record AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: 30-Day Notice and request for comments; Extension of an existing collection of information. SUMMARY: U.S....

  19. The importance of work or productive activity in life care planning and case management

    PubMed Central

    Reid, Christine; Riddick-Grisham, Susan

    2015-01-01

    Abstract INTRODUCTION: The importance of work or productive activity for the well-being, community integration, and quality of life of people living with disabilities is addressed, with implications for life care planning and case management. BACKGROUND: The role of work or productive activity in our society, and consequences of deprivation if rehabilitation services do not address vocational effects of disabilities, is explored. A continuum of productivity options is introduced; types of vocational rehabilitation assessment processes and interventions are described. PURPOSE: The role of vocational rehabilitation services in life care planning and case management is discussed, focusing on quality of life for people living with disabilities. CONCLUSION: Rehabilitation and health care professionals should understand the importance of work or other productive activity, and support the development of appropriate plans to address those needs among people who have disabilities. PMID:26409330

  20. Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity.

    PubMed

    Offman, Marc N; Krol, Marcin; Patel, Naina; Krishnan, Shekhar; Liu, JiZhong; Saha, Vaskar; Bates, Paul A

    2011-02-03

    Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginase to resist proteolytic cleavage and at the same time improve activity. We employed a novel combination of mutant sampling using a genetic algorithm in tandem with flexibility studies using molecular dynamics to investigate the impact of lid-loop and mutations on drug activity. Applying these methods, we successfully predicted the more active L-asparaginase mutants N24T and N24A. For the latter, a unique hydrogen bond network contributes to higher activity. Furthermore, interface mutations controlling secondary glutaminase activity demonstrated the importance of this enzymatic activity for drug cytotoxicity. All selected mutants were expressed, purified, and tested for activity and for their ability to form the active tetrameric form. By introducing the N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized drug design.

  1. The importance of domain closure for the auto-activation of ERK2

    PubMed Central

    Barr, Daniel; Oashi, Taiji; Burkhard, Kimberly; Lucius, Sarah; Samadani, Ramin; Zhang, Jun; Shapiro, Paul; MacKerell, Alexander D.; van der Vaart, Arjan

    2011-01-01

    Extracellular signal-regulated kinases-1 and 2 (ERK1/2) play a critical role in regulating cell division and have been implicated in cancer. In addition to activation by the MAPK/ERK kinases 1 and 2 (MEK1/2), certain mutants of ERK2 can be activated by auto-phosphorylation. To identify the mechanism of auto-activation, we have performed a series of molecular dynamics simulations of ERK1/2 in various stages of activation as well as the constitutively active Q103A, I84A, L73P and R65S ERK2 mutants. Our simulations indicate the importance of domain closure for auto-activation and activity regulation, with that event occurring prior to folding of the activation lip and of loop L16. Results indicate that the second phosphorylation event to T183 disrupts hydrogen bonding involving D334 thereby allowing the kinase to lock into the active conformation. Based on the simulations, three predictions were made: G83A was suggested to impede activation, K162M was suggested to perturb the interface between the N and C-domain leading to activation, and Q64C was hypothesized to stop folding of loop L16 thereby perturbing the homodimerization interface. Functional analysis of the mutants validated the predictions concerning the G83A and Q64C mutants. The K162M mutant did not autoactivate as predicted however, which may be due to the location of the residue on the protein surface near the ED substrate docking domain. PMID:21842857

  2. Mast cells enhance T cell activation: Importance of mast cell-derived TNF

    NASA Astrophysics Data System (ADS)

    Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

    2005-05-01

    Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

  3. A microRNA imparts robustness against environmental fluctuation during development.

    PubMed

    Li, Xin; Cassidy, Justin J; Reinke, Catherine A; Fischboeck, Stephen; Carthew, Richard W

    2009-04-17

    The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila, in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found that miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux. We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks.

  4. Axial force imparted by a current-free magnetically expanding plasma

    SciTech Connect

    Takahashi, Kazunori; Lafleur, Trevor; Charles, Christine; Alexander, Peter; Boswell, Rod W.

    2012-08-15

    The axial force imparted from a magnetically expanding, current-free, radiofrequency plasma is directly measured. For an argon gas flow rate of 25 sccm and an effective rf input power of {approx}800W, a maximum force of {approx}6mN is obtained; {approx}3mN of which is transmitted via the expanding magnetic field. The measured forces are reasonably compared with a simple fluid model associated with the measured electron pressure. The model suggests that the total force is the sum of an electron pressure inside the source and a Lorentz force due to the electron diamagnetic drift current and the applied radial magnetic field. It is shown that the Lorentz force is greatest near the magnetic nozzle surface where the radial pressure gradient is largest.

  5. The importance of myeloperoxidase enzyme activity in the pathogenesis of Crimean-Congo haemorrhagic fever.

    PubMed

    Guven, F M K; Aydin, H; Yildiz, G; Engin, A; Celik, V K; Bakir, D; Deveci, K

    2013-03-01

    Crimean-Congo haemorrhagic fever (CCHF) is a disease with a severe course including acute viral haemorrhagic fever, ecchymosis, thrombocytopenia, hepatic function disorder and high mortality. Myeloperoxidase (MPO) is an enzyme located in neutrophil granulocytes and plays an important role in the destruction of phagocytosed micro-organisms. The aim of this study was to analyse MPO enzyme activity in CCHF cases compared with a control group. A total of 47 randomly selected CCHF patients admitted to the Department of Infectious Diseases of Cumhuriyet University Hospital in Sivas, Turkey, were studied, and as a control group, 41 age- and sex-matched individuals without any systemic disease were included in this study. MPO enzyme activity was measured in plasma and leukocytes for both groups by the ELISA method. MPO plasma and MPO leukocyte values were calculated as 57.62 ± 8.85 and 44.84 ± 9.71 in CCHF patients, and 0.79 ± 0.29 and 0.49 ± 0.11 in the controls, respectively. MPO enzyme activity was statistically significantly higher in patients with CCHF when compared to the control group. In conclusion, MPO enzyme activity is directly related to the activation of phagocytic leukocytes, and increases in both the plasma and leukocytes in CCHF patients. The increase of the MPO enzyme activity in leukocytes due to viral load leads to the destruction of the leukocyte. It is thought that MPO enzyme activity in plasma was higher in CCHF patients due to the destruction of leukocytes. MPO enzyme activity may be important in terms of the prognosis in patients with CCHF; however, more extensive studies are required on this subject.

  6. Tasco®, a Product of Ascophyllum nodosum, Imparts Thermal Stress Tolerance in Caenorhabditis elegans

    PubMed Central

    Kandasamy, Saveetha; Fan, Di; Sangha, Jatinder Singh; Khan, Wajahatullah; Evans, Franklin; Critchley, Alan T.; Prithiviraj, Balakrishnan

    2011-01-01

    Tasco®, a commercial product manufactured from the brown alga Ascophyllum nodosum, has been shown to impart thermal stress tolerance in animals. We investigated the physiological, biochemical and molecular bases of this induced thermal stress tolerance using the invertebrate animal model, Caenorhabiditis elegans. Tasco® water extract (TWE) at 300 μg/mL significantly enhanced thermal stress tolerance as well as extended the life span of C. elegans. The mean survival rate of the model animals under thermal stress (35 °C) treated with 300 μg/mL and 600 μg/mL TWE, respectively, was 68% and 71% higher than the control animals. However, the TWE treatments did not affect the nematode body length, fertility or the cellular localization of daf-16. On the contrary, TWE under thermal stress significantly increased the pharyngeal pumping rate in treated animals compared to the control. Treatment with TWE also showed differential protein expression profiles over control following 2D gel-electrophoresis analysis. Furthermore, TWE significantly altered the expression of at least 40 proteins under thermal stress; among these proteins 34 were up-regulated while six were down-regulated. Mass spectroscopy analysis of the proteins altered by TWE treatment revealed that these proteins were related to heat stress tolerance, energy metabolism and a muscle structure related protein. Among them heat shock proteins, superoxide dismutase, glutathione peroxidase, aldehyde dehydrogenase, saposin-like proteins 20, myosin regulatory light chain 1, cytochrome c oxidase RAS-like, GTP-binding protein RHO A, OS were significantly up-regulated, while eukaryotic translation initiation factor 5A-1 OS, 60S ribosomal protein L18 OS, peroxiredoxin protein 2 were down regulated by TWE treatment. These results were further validated by gene expression and reporter gene expression analyses. Overall results indicate that the water soluble components of Tasco® imparted thermal stress tolerance in the C

  7. Esterase in Imported Fire Ants, Solenopsis invicta and S. richteri (Hymenoptera: Formicidae): Activity, Kinetics and Variation

    PubMed Central

    Chen, J.; Rashid, T.; Feng, G.

    2014-01-01

    Solenopsis invicta and Solenopsis richteri are two closely related invasive ants native to South America. Despite their similarity in biology and behavior, S. invicta is a more successful invasive species. Toxic tolerance has been found to be important to the success of some invasive species. Esterases play a crucial role in toxic tolerance of insects. Hence, we hypothesized that the more invasive S. invicta would have a higher esterase activity than S. richteri. Esterase activities were measured for workers and male and female alates of both ant species using α-naphthyl acetate and β-naphthyl acetate as substrates. Esterase activities in S. invicta were always significantly higher than those in S. richteri supporting our hypothesis. In S. invicta, male alates had the highest esterase activities followed by workers then female alates for both substrates. In S. richetri, for α-naphthyl acetate, male alates had the highest activity followed by female alates then workers, while for β-naphthyl acetate, female alates had the highest activity followed by male alates then workers. For workers, S. richteri showed significantly higher levels of variation about the mean esterase activity than S. invicta. However, S. invicta showed significantly higher levels of variation in both female and male alates. PMID:25408118

  8. The Importance of Landscape Elements for Bat Activity and Species Richness in Agricultural Areas

    PubMed Central

    Heim, Olga; Treitler, Julia T.; Tschapka, Marco; Knörnschild, Mirjam; Jung, Kirsten

    2015-01-01

    Landscape heterogeneity is regarded as a key factor for maintaining biodiversity and ecosystem function in production landscapes. We investigated whether grassland sites at close vicinity to forested areas are more frequently used by bats. Considering that bats are important consumers of herbivorous insects, including agricultural pest, this is important for sustainable land management. Bat activity and species richness were assessed using repeated monitoring from May to September in 2010 with acoustic monitoring surveys on 50 grassland sites in the Biosphere Reserve Schorfheide-Chorin (North-East Germany). Using spatial analysis (GIS), we measured the closest distance of each grassland site to potentially connecting landscape elements (e.g., trees, linear vegetation, groves, running and standing water). In addition, we assessed the distance to and the percent land cover of forest remnants and urban areas in a 200 m buffer around the recording sites to address differences in the local landscape setting. Species richness and bat activity increased significantly with higher forest land cover in the 200 m buffer and at smaller distance to forested areas. Moreover, species richness increased in proximity to tree groves. Larger amount of forest land cover and smaller distance to forest also resulted in a higher activity of bats on grassland sites in the beginning of the year during May, June and July. Landscape elements near grassland sites also influenced species composition of bats and species richness of functional groups (open, edge and narrow space foragers). Our results highlight the importance of forested areas, and suggest that agricultural grasslands that are closer to forest remnants might be better buffered against outbreaks of agricultural pest insects due to higher species richness and higher bat activity. Furthermore, our data reveals that even for highly mobile species such as bats, a very dense network of connecting elements within the landscape is

  9. The Importance of Landscape Elements for Bat Activity and Species Richness in Agricultural Areas.

    PubMed

    Heim, Olga; Treitler, Julia T; Tschapka, Marco; Knörnschild, Mirjam; Jung, Kirsten

    2015-01-01

    Landscape heterogeneity is regarded as a key factor for maintaining biodiversity and ecosystem function in production landscapes. We investigated whether grassland sites at close vicinity to forested areas are more frequently used by bats. Considering that bats are important consumers of herbivorous insects, including agricultural pest, this is important for sustainable land management. Bat activity and species richness were assessed using repeated monitoring from May to September in 2010 with acoustic monitoring surveys on 50 grassland sites in the Biosphere Reserve Schorfheide-Chorin (North-East Germany). Using spatial analysis (GIS), we measured the closest distance of each grassland site to potentially connecting landscape elements (e.g., trees, linear vegetation, groves, running and standing water). In addition, we assessed the distance to and the percent land cover of forest remnants and urban areas in a 200 m buffer around the recording sites to address differences in the local landscape setting. Species richness and bat activity increased significantly with higher forest land cover in the 200 m buffer and at smaller distance to forested areas. Moreover, species richness increased in proximity to tree groves. Larger amount of forest land cover and smaller distance to forest also resulted in a higher activity of bats on grassland sites in the beginning of the year during May, June and July. Landscape elements near grassland sites also influenced species composition of bats and species richness of functional groups (open, edge and narrow space foragers). Our results highlight the importance of forested areas, and suggest that agricultural grasslands that are closer to forest remnants might be better buffered against outbreaks of agricultural pest insects due to higher species richness and higher bat activity. Furthermore, our data reveals that even for highly mobile species such as bats, a very dense network of connecting elements within the landscape is

  10. [Social support and physical activity in adolescents from public schools: the importance of family and friends].

    PubMed

    Prado, Crisley Vanessa; Lima, Alex Vieira; Fermino, Rogério César; Añez, Ciro Romelio Rodriguez; Reis, Rodrigo Siqueira

    2014-04-01

    The aim of this study was to verify the association between different types and sources of social support and physical activity among adolescents from Curitiba, Paraná State, Brazil. A school-based survey was conducted with a representative sample of adolescents from public schools (n = 1,469). Multiple regression models were used to test the association between weekly frequency and sources of social support from family and friends and weekly frequency of physical activity. Among boys, frequent company of family (PR: 2.88; 95%CI: 2.00-4.13) and friends (PR: 5.46; 95%CI: 2.33-12.78) and positive reinforcement from friends (PR: 1.81; 95%CI: 1.18-2.77) were positively associated with physical activity. Sporadic invitation by the family was negatively associated with physical activity (PR: 0.66; 95%CI: 0.46-1.14). For girls, frequent company of family (PR: 3.39; 95%CI: 1.49-7.69) and friends (PR: 4.06; 95%CI: 2.22-7.45) increased the likelihood of physical activity. Company of friends was the most important type of social support for physical activity among these adolescents.

  11. Mitochondria play an important role in the cell proliferation suppressing activity of berberine

    PubMed Central

    Yan, Xiao-Jin; Yu, Xuan; Wang, Xin-Pei; Jiang, Jing-Fei; Yuan, Zhi-Yi; Lu, Xi; Lei, Fan; Xing, Dong-Ming

    2017-01-01

    After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism. PMID:28181523

  12. Induction of apoptosis by ribosome inactivating proteins: importance of N-glycosidase activity.

    PubMed

    Das, Mrinal Kumar; Sharma, Radhey Shyam; Mishra, Vandana

    2012-03-01

    Apoptotic cell death is a fundamental process in the development and physiological homeostasis of multicellular organisms. It is associated with control of cell numbers in tissues and organs during development, with cell turnover, and with response to infection. Molecules that trigger this process in continuously proliferating cancer cells can be used as chemotherapeutic agents. Ribosome inactivating proteins (RIPs) that inhibit translation in a cell by depurinating (N-glycosidase activity) the 28S rRNA are known to serve as apoptosis inducers. However, the role of depurination activity of the RIPs in apoptosis induction is still controversial. Presently, there are three different hypotheses which propose that depurination is: (1) essential, (2) essential but not the sole factor, or (3) not essential for apoptosis induction. This article reviews various experimental outcomes on the importance of N-glycosidase activity of RIPs in the induction of apoptosis.

  13. The importance of thiopurine methyltransferase activity for the use of azathioprine in transplant recipients.

    PubMed

    Chocair, P R; Duley, J A; Simmonds, H A; Cameron, J S

    1992-05-01

    immunosuppression apparently occurred, based on low catabolism of the drug. We conclude that total intolerance to azathioprine is rare and usually appears in patients with very low TPMT activities. Our results also suggest that the wide range of TPMT activity may be an important factor in determining long-term graft survival in azathioprine-treated patients; those with high activity might benefit from doses near the upper limit generally recommended.

  14. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth.

  15. Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure.

    PubMed

    Kumagai, Hiroo; Oshima, Naoki; Matsuura, Tomokazu; Iigaya, Kamon; Imai, Masaki; Onimaru, Hiroshi; Sakata, Katsufumi; Osaka, Motohisa; Onami, Toshiko; Takimoto, Chie; Kamayachi, Tadashi; Itoh, Hiroshi; Saruta, Takao

    2012-02-01

    Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy.

  16. Cognitive activities during adulthood are more important than education in building reserve.

    PubMed

    Reed, Bruce R; Dowling, Maritza; Tomaszewski Farias, Sarah; Sonnen, Joshua; Strauss, Milton; Schneider, Julie A; Bennett, David A; Mungas, Dan

    2011-07-01

    Cognitive reserve is thought to reflect life experiences. Which experiences contribute to reserve and their relative importance is not understood. Subjects were 652 autopsied cases from the Rush Memory and Aging Project and the Religious Orders Study. Reserve was defined as the residual variance of the regressions of cognitive factors on brain pathology and was captured in a latent variable that was regressed on potential determinants of reserve. Neuropathology variables included Alzheimer's disease markers, Lewy bodies, infarcts, microinfarcts, and brain weight. Cognition was measured with six cognitive domain scores. Determinants of reserve were socioeconomic status (SES), education, leisure cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in late life. The four exogenous predictors of reserve were weakly to moderately inter-correlated. In a multivariate model, all except SES had statistically significant effects on Reserve, the strongest of which were CA40 (β = .31) and CAbaseline (β = .28). The Education effect was negative in the full model (β = -.25). Results suggest that leisure cognitive activities throughout adulthood are more important than education in determining reserve. Discrepancies between cognitive activity and education may be informative in estimating late life reserve.

  17. Determination of Importance Evaluation for Exploratory Studies Facility (ESF) Subsurface Testing Activities

    SciTech Connect

    C.J. Byrne

    2001-02-20

    This Determination of Importance Evaluation (DIE) applies to the Subsurface Exploratory Studies Facility (ESF), encompassing the Topopah Spring (TS) Loop from Station 0+00 meters (m) at the North Portal to breakthrough at the South Portal (approximately 78+77 m), and ancillary test and operation support areas including the Enhanced Characterization of the Repository Block (ECRB) Cross Drift. This evaluation applies specifically to site characterization testing activities ongoing and planned in the Subsurface ESF. ESF site characterization activities are being performed to obtain the information necessary to determine whether the Yucca Mountain Site is suitable as a geologic repository for spent nuclear fuel and high-level radioactive waste. A more detailed description of these testing activities is provided in Section 6 of this DIE. Generally, the construction and operation of excavations associated with these testing activities are evaluated in the DIE for the Subsurface ESF (CRWMS M&O 1999a) and the DIE for the ESF ECRB Cross Drift (CRWMS M&O 2000a). The scope of this DIE also entails the proposed Unsaturated Zone (UZ) Transport Test at Busted Butte. Although, not a part of the TS Loop or ECRB Cross Drift, the associated testing activities are Subsurface testing activities. Busted Butte is located to the south south-east of the TS Loop and is outside the Conceptual Controlled Area Boundary (CCAB). These activities provide access to the Calico Hills (CH) geologic structure. In the case of Busted Butte, construction and operation of excavations are evaluated herein (since this activity was not previously evaluated in CRWMS M&O 1999a). The objectives of this DIE are to determine whether Subsurface ESF testing, and associated activities, could potentially impact site characterization testing and/or the waste isolation capabilities of the site. Controls needed to limit any potential impacts are identified in Section 13. The validity and veracity of the individual

  18. Determination of Importance Evaluation for Exploratory Studies Facility (ESF) Subsurface Testing Activities

    SciTech Connect

    S. Goodin

    2002-07-22

    This Determination of Importance Evaluation (DIE) applies to the Subsurface Exploratory Studies Facility (ESF), encompassing the Topopah Spring (TS) Loop from Station 0+00 meters (m) at the North Portal to breakthrough at the South Portal (approximately 78+77 m), and ancillary test and operation support areas including the Enhanced Characterization of the Repository Block (ECRB) Cross Drift. This evaluation applies specifically to site characterization testing activities ongoing and planned in the Subsurface ESF. ESF site characterization activities are being performed to obtain the information necessary to determine whether the Yucca Mountain Site is suitable as a geologic repository for spent nuclear fuel and high-level radioactive waste. A more detailed description of these testing activities is provided in Section 6 of this DIE. Generally, the construction and operation of excavations associated with these testing activities are evaluated in the DIE for the Subsurface ESF (CRWMS M&O 1999a) and the DIE for the ESF ECRB Cross Drift (CRWMS M&O 2000a). The scope of this DIE also entails the proposed Unsaturated Zone (UZ) Transport Test at Busted Butte. Although, not a part of the TS Loop or ECRB Cross Drift, the associated testing activities are Subsurface testing activities. Busted Butte is located to the south south-east of the TS Loop and is outside the Conceptual Controlled Area Boundary (CCAB). These activities provide access to the Calico Hills (CH) geologic structure. In the case of Busted Butte, construction and operation of excavations are evaluated herein (since this activity was not previously evaluated in CRWMS M&O 1999a). The objectives of this DIE are to determine whether Subsurface ESF testing, and associated activities, could potentially impact site characterization testing and/or the waste isolation capabilities of the site. Controls needed to limit any potential impacts are identified in Section 13. The validity and veracity of the individual

  19. Activity and biological effects of neem products against arthropods of medical and veterinary importance.

    PubMed

    Mulla, M S; Su, T

    1999-06-01

    Botanical insecticides are relatively safe and degradable, and are readily available sources of biopesticides. The most prominent phytochemical pesticides in recent years are those derived from neem trees, which have been studied extensively in the fields of entomology and phytochemistry, and have uses for medicinal and cosmetic purposes. The neem products have been obtained from several species of neem trees in the family Meliaceae. Six species in this family have been the subject of botanical pesticide research. They are Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia volkensii Gürke. The Meliaceae, especially A. indica (Indian neem tree), contains at least 35 biologically active principles. Azadirachtin is the predominant insecticidal active ingredient in the seed, leaves, and other parts of the neem tree. Azadirachtin and other compounds in neem products exhibit various modes of action against insects such as antifeedancy, growth regulation, fecundity suppression and sterilization, oviposition repellency or attractancy, changes in biological fitness, and blocking development of vector-borne pathogens. Some of these bioactivity parameters of neem products have been investigated at least in some species of insects of medical and veterinary importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice, and others. Here we review, synthesize, and analyze published information on the activity, modes of action, and other biological effects of neem products against arthropods of medical and veterinary importance. The amount of information on the activity, use, and application of neem products for the control of disease vectors and human and animal pests is limited. Additional research is needed to determine the potential usefulness of neem products in vector control programs.

  20. A microRNA Imparts Robustness Against Environmental Fluctuation During Development

    PubMed Central

    Li, Xin; Cassidy, Justin J.; Reinke, Catherine A.; Fischboeck, Stephen; Carthew, Richard W.

    2009-01-01

    The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila, in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found that miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux. We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks. PMID:19379693

  1. Nanoscale Topography on Black Titanium Imparts Multi-biofunctional Properties for Orthopedic Applications

    PubMed Central

    Hasan, Jafar; Jain, Shubham; Chatterjee, Kaushik

    2017-01-01

    We have developed a chlorine based reactive ion etching process to yield randomly oriented anisotropic nanostructures that render the titanium metal surface ‘black’ similar to that of black silicon. The surface appears black due to the nanostructures in contrast to the conventional shiny surface of titanium. The nanostructures were found to kill bacteria on contact by mechanically rupturing the cells as has been observed previously on wings of certain insects. The etching was optimized to yield nanostructures of ≈1 μm height for maximal bactericidal efficiency without compromising cytocompatibility. Within 4 hours of contact with the black titanium surface, 95% ± 5% of E. coli, 98% ± 2% of P. aeruginosa, 92% ± 5% of M. smegmatis and 22% ± 8% of S. aureus cells that had attached were killed. The killing efficiency for the S. aureus increased to 76% ± 4% when the cells were allowed to adhere up to 24 hours. The black titanium supported the attachment and proliferation of human mesenchymal stem cells and augmented osteogenic lineage commitment in vitro. Thus, the bioinspired nanostructures on black titanium impart multi-biofunctional properties toward engineering the next-generation biomaterials for orthopedic implants. PMID:28112235

  2. Nanoscale Topography on Black Titanium Imparts Multi-biofunctional Properties for Orthopedic Applications

    NASA Astrophysics Data System (ADS)

    Hasan, Jafar; Jain, Shubham; Chatterjee, Kaushik

    2017-01-01

    We have developed a chlorine based reactive ion etching process to yield randomly oriented anisotropic nanostructures that render the titanium metal surface ‘black’ similar to that of black silicon. The surface appears black due to the nanostructures in contrast to the conventional shiny surface of titanium. The nanostructures were found to kill bacteria on contact by mechanically rupturing the cells as has been observed previously on wings of certain insects. The etching was optimized to yield nanostructures of ≈1 μm height for maximal bactericidal efficiency without compromising cytocompatibility. Within 4 hours of contact with the black titanium surface, 95% ± 5% of E. coli, 98% ± 2% of P. aeruginosa, 92% ± 5% of M. smegmatis and 22% ± 8% of S. aureus cells that had attached were killed. The killing efficiency for the S. aureus increased to 76% ± 4% when the cells were allowed to adhere up to 24 hours. The black titanium supported the attachment and proliferation of human mesenchymal stem cells and augmented osteogenic lineage commitment in vitro. Thus, the bioinspired nanostructures on black titanium impart multi-biofunctional properties toward engineering the next-generation biomaterials for orthopedic implants.

  3. How sotolon can impart a Madeira off-flavor to aged beers.

    PubMed

    Scholtes, Caroline; Nizet, Sabrina; Collin, Sonia

    2015-03-25

    4,5-Dimethyl-3-hydroxy-2(5H)-furanone or sotolon is known to impart powerful Madeira-oxidized-curry-walnut notes to various alcoholic beverages. It has been much studied in oxidized Jura flor-sherry wines, aged Roussillon sweet wines, and old Port wines, in which it contributes to the characteristic "Madeira-oxidized" aroma of these beverages. No scientific paper describes how sotolon might be involved in the Madeira off-flavor found in aged beers. The specific extraction procedure applied here allowed us to quantify this lactone in 7 special beers, at levels sometimes well above its threshold (from 5 to 42 μg/L after 6, 12, 18, and 24 months of natural aging, while unquantifiable in fresh beer). Investigation of spiked beers led us to highlight the key role of pro-oxidants and acetaldehyde. Addition of ascorbic acid without sulfites should be avoided by brewers, as the former would intensify sotolon synthesis. Acetoin, a beer fermentation byproduct, also emerged as possible precursor in beer when combined with serine.

  4. Bioturbation effects of Corophium volutator: Importance of density and behavioural activity

    NASA Astrophysics Data System (ADS)

    De Backer, A.; Van Coillie, F.; Montserrat, F.; Provoost, P.; Van Colen, C.; Vincx, M.; Degraer, S.

    2011-01-01

    Bioturbation is one of the major processes influencing ecosystem functioning. Population parameters such as species density, burrow density and species-specific life modes, determine the impact of bioturbation on the ecosystem. A laboratory experiment was developed, using microcosms mimicking a marine intertidal sediment-water interface which allowed for quantification of different population parameters. The vertical redistribution, bioturbation rate and maximum penetration depth of two sizes (41 and 129 μm) of luminophores were measured in five treatments (control, low density of burrows with and without Corophium (1989 ind./m 2), and high density of burrows with and without Corophium (14,921 ind./m 2)) after 1, 7 and 14 days. Results indicate that the behavioural activities of Corophium are of the utmost importance in sediment reworking, since they contributed to a five-fold increase in bioturbation rate compared to the passive transport induced by the static structure of the burrows. Furthermore, density is an important parameter because only high densities play a prominent role in particle transport and hence in organic matter processing, while the role of low Corophium densities is limited in sediment reworking. No evidence for differentiation in sediment size fractions was observed. Finally, bioturbation rates in this study were low compared to other studies, and these results suggest an influence of the tidal rhythmicity in the behavioural activity of Corophium on the bioturbation rate.

  5. The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity

    SciTech Connect

    Meissner, Torsten B.; Li, Amy; Liu, Yuen-Joyce; Gagnon, Etienne; Kobayashi, Koichi S.

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer NLRC5 requires an intact NLS for its function as MHC class I transactivator. Black-Right-Pointing-Pointer Nuclear presence of NLRC5 is required for MHC class I induction. Black-Right-Pointing-Pointer Nucleotide-binding controls nuclear import and transactivation activity of NLRC5. -- Abstract: Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.

  6. Ovarian hormones, but not fluoxetine, impart resilience within a chronic unpredictable stress model in middle-aged female rats.

    PubMed

    Mahmoud, Rand; Wainwright, Steven R; Chaiton, Jessica A; Lieblich, Stephanie E; Galea, Liisa A M

    2016-08-01

    Depression is more prevalent in women than in men, and women are at a heightened risk for depression during the postpartum and perimenopause. There is also evidence to suggest that the ovarian hormone milieu may dictate antidepressant efficacy. Thus, it is important to investigate the role of ovarian hormones in the pathogenesis of depression and in the mechanisms that may underlie antidepressant efficacy. In the present study, we used 10-month-old female Sprague-Dawley rats to examine the effects of long-term ovarian hormone deprivation on the development of depressive-like endophenotypes after chronic stress, and on antidepressant efficacy. Four months following ovariectomy (OVX) or sham surgery, all rats were subjected to 6 weeks of chronic unpredictable stress (CUS). During the last 3 weeks of CUS, rats received daily injections of fluoxetine (5 mg/kg) or vehicle. All rats were assessed on measures of anxiety- and depressive-like behavior, hypothalamic-pituitary-adrenal (HPA) negative feedback inhibition, and on markers of neurogenesis and microglia in the dentate gyrus. Our findings demonstrate that long-term ovarian hormone deprivation increased anxiety and depressive-like behavior, as seen by increased immobility in the forced swim test and latency to feed in the novelty suppressed feeding test, and decreased sucrose preference. Further, long-term OVX resulted in impaired HPA negative feedback inhibition, as seen in the dexamethasone suppression test. Fluoxetine treatment showed limited behavioral and neuroendocrine efficacy, however it reduced microglial (Iba-1) expression, and increased cell proliferation, neurogenesis (via cell survival), and the expression of the polysialylated neuronal cell adhesion molecule (PSA-NCAM) in the dentate gyrus, although these effects varied by region (dorsal, ventral) and ovarian status. Taken together, our findings demonstrate that ovarian hormones may impart resilience against the behavioral and neuroendocrine

  7. Premonolayer oxidation of nanostructured gold: an important factor influencing electrocatalytic activity.

    PubMed

    O'Mullane, Anthony P; Ippolito, Samuel J; Sabri, Ylias M; Bansal, Vipul; Bhargava, Suresh K

    2009-04-09

    The study of the electrodeposition of polycrystalline gold in aqueous solution is important from the viewpoint that in electrocatalysis applications ill-defined micro- and nanostructured surfaces are often employed. In this work, the morphology of gold was controlled by the electrodeposition potential and the introduction of Pb(CH3COO)2 x 3H2O into the plating solution to give either smooth or nanostructured gold crystallites or large dendritic structures which have been characterized by scanning electron microscopy (SEM). The latter structures were achieved through a novel in situ galvanic replacement of lead with AuCl4-(aq) during the course of gold electrodeposition. The electrochemical behavior of electrodeposited gold in the double layer region was studied in acidic and alkaline media and related to electrocatalytic performance for the oxidation of hydrogen peroxide and methanol. It was found that electrodeposited gold is a significantly better electrocatalyst than a polished gold electrode; however, performance is highly dependent on the chosen deposition parameters. The fabrication of a deposit with highly active surface states, comparable to those achieved at severely disrupted metal surfaces through thermal and electrochemical methods, does not result in the most effective electrocatalyst. This is due to significant premonolayer oxidation that occurs in the double layer region of the electrodeposited gold. In particular, in alkaline solution, where gold usually shows the most electrocatalytic activity, these active surface states may be overoxidized and inhibit the electrocatalytic reaction. However, the activity and morphology of an electrodeposited film can be tailored whereby electrodeposited gold that exhibits nanostructure within the crystallites on the surface demonstrated enhanced electrocatalytic activity compared to smaller smooth gold crystallites and larger dendritic structures in potential regions well within the double layer region.

  8. Structural features important for the biological activity of the potassium channel blocking dendrotoxins.

    PubMed

    Hollecker, M; Marshall, D L; Harvey, A L

    1993-10-01

    1. Dendrotoxins from mamba snake venoms are small proteins that block neuronal K+ channels. In order to investigate structural features associated with their biological activity, partially folded versions of dendrotoxins I and K from black mamba (Dendroaspis polylepis) were prepared by selectively reducing one or more of their three S-S bonds. 2. The modified toxins were tested for ability to compete with 125I-labelled native toxin I to high affinity binding sites on rat brain synaptosomal membranes and for the ability to increase acetylcholine release in a neuromuscular preparation. 3. Binding affinity increased progressively as the toxins folded to the native conformation and the most biologically active of the modified species were those in which only the disulphide bond between residues 14 and 38 was not formed. These intermediates had native-like conformations as determined by circular dichroism but still had about 5-10 times lower affinity than native toxins. 4. Addition of negatively charged groups to block the free sulthydryls at positions 14 and 38 caused a further, marked loss of activity. 5. The results are consistent with the existence of two important regions in the dendrotoxin molecules. The region containing two of the disulphide bonds (around Cys5-Cys55 and Cys30-Cys51) and much of the secondary structure is essential for the binding affinity of the toxins, while the region around Cys14 and Cys38, equivalent to part of the antiprotease site of the homologous protease inhibitor from bovine pancreas (BPTI), plays an important role in the potency of dendrotoxins.

  9. 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

  10. Activity of bifenthrin, chlorfenapyr, fipronil, and thiamethoxam against red imported fire ants (Hymenoptera: Formicidae).

    PubMed

    Wiltz, B A; Suiter, D R; Gardner, W A

    2010-06-01

    Bifenthrin, chlorfenapyr, fipronil, and thiamethoxam were evaluated for activity against the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae). Mobility impairment and lethal times were determined after topical treatments. Both immobilization and mortality occurred most quickly with bifenthrin, followed by thiamethoxam, chlorfenapyr, and fipronil. Mortality due to horizontal exposure was evaluated at 10, 20, or 30 degrees C, with three ratios of topically treated donor ant corpses to live recipients (5, 10, or 20% donors). Bifenthrin had the greatest horizontal activity of the chemicals tested. For chlorfenapyr, the only treatments having higher mortality than controls were the highest percentage donors at either 10 or 30 degrees C. Horizontal activity of fipronil was temperature dependent only with the highest proportion of donors and was lower than that ofbifenthrin but higher than that of chlorfenapyr or thiamethoxam. Mean mortality due to thiamethoxam was similar to that with chlorfenapyr. Significant mortality occurred in all of the 20 and 30 degrees C thiamethoxam treatments, but none of the 10 degrees C treatments. Effectiveness as a barrier was evaluated by providing a choice between bridges treated with insecticide or water. Although bifenthrin did not provide an impenetrable barrier, it was the only treatment having fewer ants than its paired control bridge. Mortality data suggest that a reduction in recruitment rather than repellency account for this result.

  11. Acute β-Adrenergic Activation Triggers Nuclear Import of Histone Deacetylase 5 and Delays Gq-induced Transcriptional Activation*

    PubMed Central

    Chang, Chia-Wei Jenny; Lee, Linda; Yu, David; Dao, Khanha; Bossuyt, Julie; Bers, Donald M.

    2013-01-01

    During hemodynamic stress, catecholamines and neurohumoral stimuli may induce co-activation of Gq-coupled receptors and β-adrenergic receptors (β-AR), leading to cardiac remodeling. Dynamic regulation of histone deacetylase 5 (HDAC5), a transcriptional repressor, is crucial during stress signaling due to its role in epigenetic control of fetal gene markers. Little is known about its regulation during acute and chronic β-AR stimulation and its cross-interaction with Gq signaling in adult cardiac myocytes. Here, we evaluate the potential cross-talk between Gq-driven and β-AR mediated signaling at the level of nucleocytoplasmic shuttling of HDAC5. We show the translocation of GFP-tagged wild type HDAC5 or mutants (S279A and S279D) in response to β-AR or Gq agonists. Isoproterenol (ISO) or PKA activation results in strong nuclear accumulation of HDAC5 in contrast to nuclear export driven by Ca2+-calmodulin protein kinase II and protein kinase D. Moreover, nuclear accumulation of HDAC5 under acute ISO/PKA signaling is dependent on phosphorylation of Ser-279 and can block subsequent Gq-mediated nuclear HDAC5 export. Intriguingly, the attenuation of Gq-induced export is abolished after chronic PKA activation, yet nuclear HDAC5 remains elevated. Last, the effect of chronic β-AR signaling on HDAC5 translocation was examined in adult myocytes from a rabbit model of heart failure, where ISO-induced nuclear import is ablated, but Gq-agonist mediated export is preserved. Acute β-AR/PKA activation protects against hypertrophic signaling by delaying Gq-mediated transcriptional activation. This serves as a key physiological control switch before allowing genetic reprogramming via HDAC5 nuclear export during more severe stress, such as heart failure. PMID:23161540

  12. Increasing ocean temperatures reduce activity patterns of a large commercially important coral reef fish.

    PubMed

    Johansen, J L; Messmer, V; Coker, D J; Hoey, A S; Pratchett, M S

    2014-04-01

    Large-bodied fish are critical for sustaining coral reef fisheries, but little is known about the vulnerability of these fish to global warming. This study examined the effects of elevated temperatures on the movement and activity patterns of the common coral trout Plectropomus leopardus (Serranidae), which is an important fishery species in tropical Australia and throughout the Indo West-Pacific. Adult fish were collected from two locations on Australia's Great Barrier Reef (23°S and 14°S) and maintained at one of four temperatures (24, 27, 30, 33 °C). Following >4 weeks acclimation, the spontaneous swimming speeds and activity patterns of individuals were recorded over a period of 12 days. At 24-27 °C, spontaneous swimming speeds of common coral trout were 0.43-0.45 body lengths per second (bls(-1)), but dropped sharply to 0.29 bls(-1) at 30 °C and 0.25 bls(-1) at 33 °C. Concurrently, individuals spent 9.3-10.6% of their time resting motionless on the bottom at 24-27 °C, but this behaviour increased to 14.0% at 30 °C and 20.0% of the time at 33 °C (mean ± SE). The impact of temperature was greatest for smaller individuals (<45 cm TL), showing significant changes to swimming speeds across every temperature tested, while medium (45-55 cm TL) and large individuals (>55 cm TL) were first affected by 30 °C and 33 °C, respectively. Importantly, there was some indication that populations can adapt to elevated temperature if presented with adequate time, as the high-latitude population decreased significantly in swimming speeds at both 30 °C and 33 °C, while the low-latitude population only showed significant reductions at 33 °C. Given that movement and activity patterns of large mobile species are directly related to prey encounter rates, ability to capture prey and avoid predators, any reductions in activity patterns are likely to reduce overall foraging and energy intake, limit the energy available for growth and reproduction, and affect the fitness and

  13. Importance of neutron energy distribution in borehole activation analysis in relatively dry, low-porosity rocks

    USGS Publications Warehouse

    Senftle, F.E.; Moxham, R.M.; Tanner, A.B.; Philbin, P.W.; Boynton, G.R.; Wager, R.E.

    1977-01-01

    To evaluate the importance of variations in the neutron energy distribution in borehole activation analysis, capture gamma-ray measurements were made in relatively dry, low-porosity gabbro of the Duluth Complex. Although sections of over a meter of solid rock were encountered in the borehole, there was significant fracturing with interstitial water leading to a substantial variation of water with depth in the borehole. The linear-correlation coefficients calculated for the peak intensities of several elements compared to the chemical core analyses were generally poor throughout the depth investigated. The data suggest and arguments are given which indicate that the variation of the thermal-to-intermediate-to-fast neutron flux density as a function of borehole depth is a serious source of error and is a major cause of the changes observed in the capture gamma-ray peak intensities. These variations in neutron energy may also cause a shift in the observed capture gamma-ray energy.

  14. [Antibacterial and antifungal activity of Salvia apiana against clinically important microorganisms].

    PubMed

    Córdova-Guerrero, Iván; Aragon-Martinez, Othoniel H; Díaz-Rubio, Laura; Franco-Cabrera, Santiago; Serafín-Higuera, Nicolas A; Pozos-Guillén, Amaury; Soto-Castro, Tely A; Martinez-Morales, Flavio; Isiordia-Espinoza, Mario

    Due to the great global concern regarding bacterial resistance to antibiotics, an ongoing search for new molecules having antibacterial activity is necessary. This study evaluated the antibacterial and anticandidal effects of a hexane extract from the root of Salvia apiana. Salvia extracts at concentrations of 27, 13.5, 6.8 and 3.4mg/ml caused growth inhibition of Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis and Candida albicans. However, no significant effect was observed on Escherichia coli and Candida tropicalis in comparison to vehicle. It was here demonstrated for the first time that Salvia apiana has an important antimicrobial effect on human pathogens of great clinical value, thus opening the field to continue the evaluation of this lamiaceous plant for its future use as a therapeutic agent.

  15. Bubble Wrap for Bullets: The Stability Imparted by a Thin Magnetic Layer

    NASA Astrophysics Data System (ADS)

    Dursi, L. J.

    2007-11-01

    There has been significant recent work by several authors which examines a situation where a thin magnetic layer is ``draped'' over a core merging into a larger cluster; the same process also appears to be at work in a bubble rising from the cluster center. Such a thin magnetic layer could thermally isolate the core from the cluster medium, but only if the same shear process which generates the layer does not later disrupt it. On the other hand, if the magnetized layer can stabilize against the shear instabilities, then the magnetic layer can have the additional dynamical effect of reducing the shear-driven mixing of the core's material during the merger process. These arguments could apply equally well to underdense cluster bubbles, which would be even more prone to disruption. While it is well known that magnetic fields can suppress instabilities, it is less clear that a thin layer can suppress instabilities on scales significantly larger than its thickness. We consider here the stability imparted by a thin magnetized layer. We investigate this question in the most favorable case, that of two dimensions, where the magnetic field can most strongly affect the stability. We find that in this case such a layer can have a significant stabilizing effect even on modes with wavelengths λ much larger than the thickness of the layer l. To stabilize modes with λ~10l requires only that the Alfvén speed in the magnetized layer is comparable to or greater than the relevant destabilizing velocity-the shear velocity in the case of pure Kelvin-Helmholtz-like instability or a typical buoyancy velocity in the case of pure Rayleigh-Taylor-like instability. We confirm our calculations with two-dimensional numerical experiments using the Athena code.

  16. Ultrasound imparted air-recoil resonance (UIAR) method for acoustic power estimation: theory and experiment.

    PubMed

    Kaiplavil, Sreekumar; Rivens, Ian; ter Haar, Gail

    2013-07-01

    Ultrasound imparted air-recoil resonance (UIAR), a new method for acoustic power estimation, is introduced with emphasis on therapeutic high-intensity focused ultrasound (HIFU) monitoring applications. Advantages of this approach over existing practices include fast response; electrical and magnetic inertness, and hence MRI compatibility; portability; high damage threshold and immunity to vibration and interference; low cost; etc. The angle of incidence should be fixed for accurate measurement. However, the transducer-detector pair can be aligned in any direction with respect to the force of gravity. In this sense, the operation of the device is orientation independent. The acoustic response of a pneumatically coupled pair of Helmholtz resonators, with one of them acting as the sensor head, is used for the estimation of acoustic power. The principle is valid in the case of pulsed/ burst as well as continuous ultrasound exposure, the former being more sensitive and accurate. An electro-acoustic theory has been developed for describing the dynamics of pressure flow and resonance in the system considering various thermo- viscous loss mechanisms. Experimental observations are found to be in agreement with theoretical results. Assuming the window damage threshold (~10 J·mm(-2)) and accuracy of RF power estimation are the upper and lower scale-limiting factors, the performance of the device was examined for an RF power range of 5 mW to 100 W with a HIFU transducer operating at 1.70 MHz, and an average nonlinearity of ~1.5% was observed. The device is also sensitive to sub-milliwatt powers. The frequency response was analyzed at 0.85, 1.70, 2.55, and 3.40 MHz and the results are presented with respective theoretical estimates. Typical response time is in the millisecond regime. Output drift is about 3% for resonant and 5% for nonresonant modes. The principle has been optimized to demonstrate a general-purpose acoustic power meter.

  17. Hydrothermal activity at slow-spreading ridges: variability and importance of magmatic controls

    NASA Astrophysics Data System (ADS)

    Escartin, Javier

    2016-04-01

    less studied, similar hydrothermal systems are found elsewhere associated to other central volcanoes along the ridge axis (e.g., Menez Gwenn at the Mid-Atlantic Ridge and Soria Mornia or Troll Wall at the Arctic Ridges). Long-lived hydrothermal activity plays an important role in controlling the thermal structure of the lithosphere and its accretion at and near-axis, and also determining the distribution and biogeography of vent communities. Along slow-spreading segments, long-lived hydrothermal activity can be provided both by volcanic systems (e.g., Lucky Strike) and tectonic systems (oceanic detachment faults). While magmatic and hydrothermal activity is relatively well understood now in volcanic systems (e.g., Lucky Strike), tectonic systems (oceanic detachment faults) require further integrated studies to constrain the links between long-lived localization of deformation along oceanic detachment faults, hydrothermal activity, and origin and nature of off-axis heat sources animating hydrothermal circulation.

  18. Using Academia-Industry Partnerships to Enhance Software Verification & Validation Education via Active Learning Tools

    ERIC Educational Resources Information Center

    Acharya, Sushil; Manohar, Priyadarshan; Wu, Peter; Schilling, Walter

    2017-01-01

    Imparting real world experiences in a software verification and validation (SV&V) course is often a challenge due to the lack of effective active learning tools. This pedagogical requirement is important because graduates are expected to develop software that meets rigorous quality standards in functional and application domains. Realizing the…

  19. The importance of self-determined motivation towards physical activity in patients with schizophrenia.

    PubMed

    Vancampfort, Davy; De Hert, Marc; Vansteenkiste, Maarten; De Herdt, Amber; Scheewe, Thomas W; Soundy, Andrew; Stubbs, Brendon; Probst, Michel

    2013-12-30

    There is a need for theoretically-based research on the motivational processes linked to the commencement and continuation of physical activity in patients with schizophrenia. Within the Self-Determination Theory (SDT) framework, we investigated the SDT tenets in these patients by examining the factor structure of the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) and by investigating associations between motivation and PA. The secondary aim was to study differences in motivation according to gender, educational level, treatment setting and disease stage. A total of 129 patients (44♀) with schizophrenia agreed to participate. Exploratory factor analysis showed sufficient convergence with the original factor for amotivation, external and introjected regulation, while identified and intrinsic regulations loaded on a single factor which we labeled "autonomous regulation". Significant positive correlations were found between the total physical activity score and the subscales amotivation (r = -0.44, P < 0.001), external regulation (r = -0.27, P < 0.001), and autonomous regulation (r = 0.57, P < 0.001). Outpatients reported more external (P < 0.05) and introjected (P < 0.05) regulations than inpatients. Our results suggest that patients' level of self-determination may play an important role in the adoption and maintenance of health promoting behaviors in patients with schizophrenia.

  20. Identification of a protein with antioxidant activity that is important for the protection against beer ageing.

    PubMed

    Wu, Ming J; Clarke, Frank M; Rogers, Peter J; Young, Paul; Sales, Narelle; O'Doherty, Patrick J; Higgins, Vincent J

    2011-01-01

    This study was carried out with fresh Australian lager beer which was sampled directly off the production line, the same samples aged for 12 weeks at 30 °C, and the vintage beer which was kept at 20 °C for 5 years. Characteristic Australian lager flavour was maintained in the fresh and vintage beers but was lost in the aged beer. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and free thiol group labelling analyses of beer proteins found that this flavour stability correlated with the presence of an unknown 10 kilodaltons (kDa) protein with a higher level of free thiols. The protein was purified by size-exclusion chromatography, then peptide sequencing and database matching identified it as the barley lipid transfer protein (LTP1). Further characterisation using diphenylpicrylhydrazyl (DPPH) free radical scavenging and a Saccharomyces cerevisiae-based antioxidant screening assay demonstrated that the LTP1 protein was active in DPPH reduction and antioxidant activity. The absence of free thiol in the aged beer indicates that the thiol functional groups within the LTP1 protein were saturated and suggests that it is important in the flavour stability of beer by maintaining reduction capacity during the ageing process.

  1. Identification of a Protein with Antioxidant Activity that is Important for the Protection against Beer Ageing

    PubMed Central

    Wu, Ming J.; Clarke, Frank M.; Rogers, Peter J.; Young, Paul; Sales, Narelle; O’Doherty, Patrick J.; Higgins, Vincent J.

    2011-01-01

    This study was carried out with fresh Australian lager beer which was sampled directly off the production line, the same samples aged for 12 weeks at 30 °C, and the vintage beer which was kept at 20 °C for 5 years. Characteristic Australian lager flavour was maintained in the fresh and vintage beers but was lost in the aged beer. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and free thiol group labelling analyses of beer proteins found that this flavour stability correlated with the presence of an unknown 10 kilodaltons (kDa) protein with a higher level of free thiols. The protein was purified by size-exclusion chromatography, then peptide sequencing and database matching identified it as the barley lipid transfer protein (LTP1). Further characterisation using diphenylpicrylhydrazyl (DPPH) free radical scavenging and a Saccharomyces cerevisiae-based antioxidant screening assay demonstrated that the LTP1 protein was active in DPPH reduction and antioxidant activity. The absence of free thiol in the aged beer indicates that the thiol functional groups within the LTP1 protein were saturated and suggests that it is important in the flavour stability of beer by maintaining reduction capacity during the ageing process. PMID:22016646

  2. The chromodomains of CHD1 are critical for enzymatic activity but less important for chromatin localization.

    PubMed

    Morettini, Stefano; Tribus, Martin; Zeilner, Anette; Sebald, Johanna; Campo-Fernandez, Beatriz; Scheran, Gabriele; Wörle, Hildegard; Podhraski, Valerie; Fyodorov, Dmitry V; Lusser, Alexandra

    2011-04-01

    The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster. A key feature of CHD1 is the presence of two chromodomains, which can bind to histone H3 methylated at lysine 4 and thus might serve to recruit and/or maintain CHD1 at the chromatin. Here, we describe genetic and biochemical approaches to the study of the Drosophila CHD1 chromodomains. We found that overall localization of CHD1 on polytene chromosomes does not appreciably change in chromodomain-mutant flies. In contrast, the chromodomains are important for transcription-independent activities of CHD1 during early embryonic development as well as for transcriptional regulation of several heat shock genes. However, neither CHD1 nor its chromodomains are needed for RNA polymerase II localization and H3K4 methylation but loss of CHD1 decreases transcription-induced histone eviction at the Hsp70 gene in vivo. Chromodomain mutations negatively affect the chromatin assembly activities of CHD1 in vitro, and they appear to be involved in linking the ATP-dependent motor to the chromatin assembly function of CHD1.

  3. Importance of the lid and cap domains for the catalytic activity of gastric lipases.

    PubMed

    Miled, N; Bussetta, C; De caro, A; Rivière, M; Berti, L; Canaan, S

    2003-09-01

    Human gastric lipase (HGL) is an enzyme secreted by the stomach, which is stable and active despite the highly acidic environment. It has been clearly established that this enzyme is responsible for 30% of the fat digestion processes occurring in human. This globular protein belongs to the alpha/beta hydrolase fold family and its catalytic serine is deeply buried under a domain called the extrusion domain, which is composed of a 'cap' domain and a segment consisting of 58 residues, which can be defined as a lid. The exact roles played by the cap and the lid domains during the catalytic step have not yet been elucidated. We have recently solved the crystal structure of the open form of the dog gastric lipase in complex with a covalent inhibitor. The detergent molecule and the inhibitor were mimicking a triglyceride substrate that would interact with residues belonging to both the cap and the lid domains. In this study, we have investigated the role of the cap and the lid domains, using site-directed mutagenesis procedures. We have produced truncated mutants lacking the lid and the cap. After expressing these mutants and purifying them, their activity was found to have decreased drastically in comparison with the wild type HGL. The lid and the cap domains play an important role in the catalytic reaction mechanism. Based on these results and the structural data (open form of DGL), we have pointed out the cap and the lid residues involved in the binding with the lipidic substrate.

  4. An important base triple anchors the substrate helix recognition surface within the Tetrahymena ribozyme active site.

    PubMed

    Szewczak, A A; Ortoleva-Donnelly, L; Zivarts, M V; Oyelere, A K; Kazantsev, A V; Strobel, S A

    1999-09-28

    Key to understanding the structural biology of catalytic RNA is determining the underlying networks of interactions that stabilize RNA folding, substrate binding, and catalysis. Here we demonstrate the existence and functional importance of a Hoogsteen base triple (U300.A97-U277), which anchors the substrate helix recognition surface within the Tetrahymena group I ribozyme active site. Nucleotide analog interference suppression analysis of the interacting functional groups shows that the U300.A97-U277 triple forms part of a network of hydrogen bonds that connect the P3 helix, the J8/7 strand, and the P1 substrate helix. Product binding and substrate cleavage kinetics experiments performed on mutant ribozymes that lack this base triple (C A-U, U G-C) or replace it with the isomorphous C(+).G-C triple show that the A97 Hoogsteen triple contributes to the stabilization of both substrate helix docking and the conformation of the ribozyme's active site. The U300. A97-U277 base triple is not formed in the recently reported crystallographic model of a portion of the group I intron, despite the presence of J8/7 and P3 in the RNA construct [Golden, B. L., Gooding, A. R., Podell, E. R. & Cech, T. R. (1998) Science 282, 259-264]. This, along with other biochemical evidence, suggests that the active site in the crystallized form of the ribozyme is not fully preorganized and that substantial rearrangement may be required for substrate helix docking and catalysis.

  5. Active Subduction on Both Coasts of Costa Rica Does not Represent an Important Tsunami Hazard

    NASA Astrophysics Data System (ADS)

    Protti, M.; Gonzalez, V.

    2007-05-01

    Costa Rica, on the southern terminus of the Middle American Trench is being affected by active subduction on both, along the Pacific coast as well as on its Caribbean coast. Three main subduction segments can be recognized along the Pacific coast: 1) under northwestern Costa Rica, off Papagayo Gulf and Nicoya peninsula, the Cocos plate is subducting under the Caribbean plate; 2) under southern Costa Rica (Osa and Burica peninsulas) the Cocos plate subducts under the Panama Block and 3) in the central Pacific coast (between Nicoya and Osa peninsulas) the Cocos plate subducts under a shear zone that marks the transition between the Caribbean and the Cocos plate. Along the Caribbean coast, south of Puerto Limon, the Caribbean plate subducts under the Panama block. Large subduction earthquakes occur under the Nicoya peninsula, Osa peninsula and south of Limon. Most of the rupture area of these large events lies below land so the deformation of the ocean floor is minimal and therefore the tsunamis they generate are small. No large subduction earthquakes occur under the central Pacific coast of Costa Rica due to the subduction of small sea mounts that act as small asperities without potential to accumulate large amounts of slip. For this reason the region between Nicoya and Osa peninsulas is not an important tsunamigenic zone.

  6. Circulating platelet-neutrophil complexes are important for subsequent neutrophil activation and migration.

    PubMed

    Kornerup, Kristin N; Salmon, Gary P; Pitchford, Simon C; Liu, Wai L; Page, Clive P

    2010-09-01

    Previous studies in our laboratory have shown that platelets are essential for the migration of eosinophils into the lungs of allergic mice, and that this is dependent on the functional expression of platelet P-selectin. We sought to investigate whether the same is true for nonallergic, acute inflammatory stimuli administered to distinct anatomic compartments. Neutrophil trafficking was induced in two models, namely zymosan-induced peritonitis and LPS-induced lung inflammation, and the platelet dependence of these responses investigated utilizing mice rendered thrombocytopenic. The relative contribution of selectins was also investigated. The results presented herein clearly show that platelet depletion (>90%) significantly inhibits neutrophil recruitment in both models. In addition, we show that P-selectin glycoprotein ligand-1, but not P-selectin, is essential for neutrophil recruitment in mice in vivo, thus suggesting the existence of different regulatory mechanisms for the recruitment of leukocyte subsets in response to allergic and nonallergic stimuli. Further studies in human blood demonstrate that low-dose prothrombotic and pro-inflammatory stimuli (CCL17 or CCL22) synergize to induce platelet and neutrophil activation, as well as the formation of platelet-neutrophil conjugates. We conclude that adhesion between platelets and neutrophils in vivo is an important event in acute inflammatory responses. Targeting this interaction may be a successful strategy for inflammatory conditions where current therapy fails to provide adequate treatment.

  7. Transmitting Sport Values: The Importance of Parental Involvement in Children’s Sport Activity

    PubMed Central

    Danioni, Francesca; Barni, Daniela; Rosnati, Rosa

    2017-01-01

    The transmission of positive values between parents and children is generally considered to be the hallmark of successful socialization. As this issue has been widely discussed but surprisingly little researched - especially with reference to core sport values - in this study we aimed to: 1) analyze adolescent athletes’ acceptance of the sport values their parents want to transmit to them (i.e., parental socialization values) and 2) examine the relationship between parental involvement in children’s sportive activity and adolescents’ acceptance of their parents’ socialization values. One hundred and seventy-two Italian adolescents (48.3% male, 51.7% female) who regularly practice team sports were asked to fill out a questionnaire which included the Youth Sport Values Questionnaire – 2 and the Parental Involvement in Sport Questionnaire. The dyadic correlations revealed that young athletes are in general willing to accept their parents’ socialization values in regards to sport. Moreover, from the relative weight analysis (a relatively new data analysis strategy), it emerged that parental involvement characterized by praise and understanding is the most important predictor of adolescents’ willingness to accept their parents’ sport values. Implications of these results and further expansion of the study are discussed. PMID:28344676

  8. Transmitting Sport Values: The Importance of Parental Involvement in Children's Sport Activity.

    PubMed

    Danioni, Francesca; Barni, Daniela; Rosnati, Rosa

    2017-03-01

    The transmission of positive values between parents and children is generally considered to be the hallmark of successful socialization. As this issue has been widely discussed but surprisingly little researched - especially with reference to core sport values - in this study we aimed to: 1) analyze adolescent athletes' acceptance of the sport values their parents want to transmit to them (i.e., parental socialization values) and 2) examine the relationship between parental involvement in children's sportive activity and adolescents' acceptance of their parents' socialization values. One hundred and seventy-two Italian adolescents (48.3% male, 51.7% female) who regularly practice team sports were asked to fill out a questionnaire which included the Youth Sport Values Questionnaire - 2 and the Parental Involvement in Sport Questionnaire. The dyadic correlations revealed that young athletes are in general willing to accept their parents' socialization values in regards to sport. Moreover, from the relative weight analysis (a relatively new data analysis strategy), it emerged that parental involvement characterized by praise and understanding is the most important predictor of adolescents' willingness to accept their parents' sport values. Implications of these results and further expansion of the study are discussed.

  9. Test-Retest Reliability and descriptive analyses of the Modified Important People and Activities (MIPA) Interview

    PubMed Central

    Zywiak, William H.; Stout, Robert L.; Braciszewski, Jordan M.; Wray, Tyler B.; Longabaugh, Richard

    2016-01-01

    Background The Important People and Activities (IPA) instrument assesses network characteristics and social support for drinking and abstinence. The IPA has garnered widespread use in the alcohol treatment field. We modified the IPA to assess HIV status, drug of choice, and IV drug use among social network members. Further, we queried frequency of unprotected sex, between the participant and network members. Aim Since this measure was modified, and the test-retest reliability of the IPA has only rarely been examined, we conducted a small substudy (n=26) to examine 1-week test-retest reliability of this measure. Methods Participants were individuals in a day treatment program with an SUD and/or AUD diagnosis. Results Drug of choice for the participants represented roughly equal thirds of heroin, cocaine, and alcohol. The sample was 62% female and 39% Latino/a. At pretest 198 persons were named on the MIPA (M=7.6 network members per subject). It was determined that 152 of the people were overlapping between the test and retest. Conclusions Percent agreement, ICCs, and kappas for the items ranged from acceptable to excellent across the two time periods. Classification of network members as positive, negative, or neutral influences on sobriety also demonstrated good to excellent kappas. PMID:27429606

  10. Small Conductance Calcium-Activated Potassium Current is Important in Transmural Repolarization of Failing Human Ventricles

    PubMed Central

    Yu, Chih-Chieh; Corr, Christopher; Shen, Changyu; Shelton, Richard; Yadava, Mrinal; Rhea, Isaac; Straka, Susan; Fishbein, Michael C.; Chen, Zhenhui; Lin, Shien-Fong; Lopshire, John C.; Chen, Peng-Sheng

    2015-01-01

    Background The transmural distribution of apamin-sensitive small conductance Ca2+-activated K+ (SK) current (IKAS) in failing human ventricles remains unclear. Methods and Results We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nM apamin administration in all wedges and after sequential administration of apamin, chromanol and E4031 in 4 wedges. Apamin prolonged APD from 363 ms [95% confidence interval (CI), 341 to 385] to 409 [CI, 385 to 434] (p<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s [CI, 30 to 42] to 32 cm/s [CI, 27 to 37] (p=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only one wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol and E4031 were 9.1% [CI, 3.9 to 14.2], 17.3% [CI, 3.1 to 31.5] and 35.9% [CI, 15.7 to 56.1], respectively. Immunohistochemical staining of subtype 2 of SK (SK2) protein showed increased expression in intercalated discs of myocytes. Conclusions SK current is important in the transmural repolarization in failing human ventricles. The magnitude of IKAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant SK2 protein in the intercalated discs of myocytes. PMID:25908692

  11. Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo.

    PubMed

    Seeliger, Stephan; Buddenkotte, Jörg; Schmidt-Choudhury, Anjona; Rosignoli, Carine; Shpacovitch, Victoria; von Arnim, Ulrike; Metze, Dieter; Rukwied, Roman; Schmelz, Martin; Paus, Ralf; Voegel, Johannes J; Schmidt, Wolfgang E; Steinhoff, Martin

    2010-11-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is an important neuropeptide and immunomodulator in various tissues. Although this peptide and its receptors (ie, VPAC1R, VPAC2R, and PAC1R) are expressed in human skin, their biological roles are unknown. Therefore, we tested whether PACAP regulates vascular responses in human skin in vivo. When injected intravenously, PACAP induced a significant, concentration-dependent vascular response (ie, flush, erythema, edema) and mediated a significant and concentration-dependent increase in intrarectal body temperature that peaked at 2.7°C. Topical application of PACAP induced marked concentration-dependent edema. Immunohistochemistry revealed a close association of PACAP-immunoreactive nerve fibers with mast cells and dermal blood vessels. VPAC1R was expressed by dermal endothelial cells, CD4+ and CD8+ T cells, mast cells, and keratinocytes, whereas VPAC2R was expressed only in keratinocytes. VPAC1R protein and mRNA were also detected in human dermal microvascular endothelial cells. The PACAP-induced change in cAMP production in these cells demonstrated VPAC1R to be functional. PACAP treatment of organ-cultured human skin strongly increased the number of CD31+ vessel cross-sections. Taken together, these results suggest that PACAP directly induces vascular responses that may be associated with neurogenic inflammation, indicating for the first time that PACAP may be a crucial vascular regulator in human skin in vivo. Antagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases with a neurogenic component.

  12. 75 FR 79342 - Taking and Importing Marine Mammals; Navy Training Activities Conducted Within the Northwest...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... exposing them to sound from mid-frequency or high frequency active sonar (MFAS/HFAS) or to underwater... frequency active sonar (MFAS/HFAS) or underwater detonations. After submitting supplemental...

  13. [Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica].

    PubMed

    Bi, Xiaolin; Du, Qiu; Di, Liuqing

    2010-02-01

    Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

  14. Protegrin structure-activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity.

    PubMed

    Ostberg, Nathan; Kaznessis, Yiannis

    2005-02-01

    The protegrin family of antimicrobial peptides is among the shortest in sequence length while remaining very active against a variety of microorganisms. The major goal of this study is to characterize easily calculated molecular properties, which quantitatively show high correlation with antibacterial activity. The peptides studied have high sequence similarity but vary in activity over more than an order of magnitude. Hence, sequence analysis alone cannot be used to predict activity for these peptides. We calculate structural properties of 62 protegrin and protegrin-analogue peptides and correlate them to experimental activities against six microbe species, as well as hemolytic and cytotoxic activities. Natural protegrins structures were compared with synthetic derivatives using homology modeling, and property descriptors were calculated to determine the characteristics that confer their antimicrobial activity. A structure-activity relationship study of all these peptides provides information about the structural properties that affect activity against different microbial species.

  15. Active faults crossing trunk pipeline routes: some important steps to avoid disaster

    NASA Astrophysics Data System (ADS)

    Besstrashnov, V. M.; Strom, A. L.

    2011-05-01

    Assessment of seismic strong motion hazard produced by earthquakes originating within causative fault zones allows rather low accuracy of localisation of these structures that can be provided by indirect evidence of fault activity. In contrast, the relevant accuracy of localisation and characterisation of active faults, capable of surface rupturing, can be achieved solely by the use of direct evidence of fault activity. This differentiation requires strict definition of what can be classified as "active fault" and the normalisation of methods used for identification and localisation of active faults crossing oil and natural gas trunk pipelines.

  16. Killer activity of yeasts isolated from natural environments against some medically important Candida species.

    PubMed

    Vadkertiová, Renata; Sláviková, Elena

    2007-01-01

    Twenty-five yeast cultures, mainly of human origin, belonging to four pathogenic yeast species--Candida albicans, Candida krusei, Candida parapsilosis, and Candida tropicalis were tested for their sensitivity to ten basidiomycetous and eleven ascomycetous yeast species isolated from the water and soil environments and from tree leaves. The best killer activity among basidiomycetous species was exhibited by Rhodotorula glutinis, and R. mucilaginosa. The other carotenoid producing species Cystofilobasidium capitatum, Sporobolomyces salmonicolor, and S. roseus were active only against about 40% of the tested strains and exhibited weak activity. The broadest killer activity among ascomycetous yeasts was shown by the strains Pichia anomala and Metschnikowia pulcherrima. The species Debaryomyces castellii, Debaryomyces hansenii, Hanseniaspora guilliermondii, Pichia membranifaciens, and Williopsis californica did not show any killer activity. The best killer activity exhibited the strains isolated from leafy material. The lowest activity pattern was found among strains originating from soil environment.

  17. Esterase in imported fire ants, Solenopsis invicata and S. richteri (Hymenoptera: Formicidae): activity, kinetics and variation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Black imported fire ant, Solenopsis richteri, is closely related to the notorious red imported fire ant, Solenopsis invicta. Despite being very similar in biology and behavior, S. invicta is a much more successful invader. In contrast to S. invicta that has invaded numberous countries and regions,...

  18. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    EPA Science Inventory

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  19. GlpC gene is responsible for biofilm formation and defense against phagocytes and imparts tolerance to pH and organic solvents in Proteus vulgaris.

    PubMed

    Wu, Y L; Liu, K S; Yin, X T; Fei, R M

    2015-09-09

    Biofilm-forming bacteria are highly resistant to antibiotics, host immune defenses, and other external conditions. The formation of biofilms plays a key role in colonization and infection. To explore the mechanism of biofilm formation, mutant strains of Proteus vulgaris XC 2 were generated by Tn5 random transposon insertion. Only one biofilm defective bacterial species was identified from among 500 mutants. Inactivation of the glpC gene coding an anaerobic glycerol-3-phosphate dehydrogenase subunit C was identified by sequence analysis of the biofilm defective strain. Differences were detected in the growth phenotypes of the wild-type and mutant strains under pH, antibiotic, and organic solvent stress conditions. Furthermore, we observed an increase in the phagocytosis of the biofilm defective strain by the mouse macrophage RAW264.7 cell line compared to the wild-type strain. This study shows that the glpC gene plays an important role in biofilm formation, in addition to imparting pH, organic solvent, and antibiotic tolerance, and defense against phagocytosis to Proteus sp. The results further clarified the mechanism of biofilm formation at the genomic level, and indicated the importance of the glpC gene in this process. This data may provide innovative therapeutic measures against P. vulgaris infections; furthermore, as an important crocodile pathogen, this study also has important significance in the protection of Chinese alligators.

  20. Preschool Teaching Staff's Opinions on the Importance of Preschool Curricular Fields of Activities, Art Genres and Visual Arts Fields

    ERIC Educational Resources Information Center

    Zupancic, Tomaž; Cagran, Branka; Mulej, Matjaž

    2015-01-01

    This article presents preschool teachers' and assistant teachers' opinions on the importance of selected fields of educational work in kindergartens. The article first highlights the importance of activities expressing artistic creativity within modern curriculums. Then, it presents an empirical study that examines the preschool teachers' and…

  1. 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.

  2. Importance of viability and attachment to an ascites tumor in the release of plasminogen activator.

    PubMed Central

    Dong, Q.; Zhou, M.; Subbarao, V.; Ts'ao, C.

    1991-01-01

    Tumor plasminogen activator (PA) has been alleged to play a role in the growth and metastasis of tumors. Before such a role can be realized, PA first must be released from tumor cells. Having determined intra- and extracellular PA and PA-inhibitor activities in an experimental pancreatic ascites tumor grown in hamsters, the release of PA from these cells was investigated. No PA activity was detected in the suspension medium of freshly isolated tumor cells; inclusion of plasminogen, fibrinogen, or collagen in the medium yielded similar negative results. On the other hand, PA activity was demonstrated to be released in a time-dependent manner from these tumor cells embedded in fibrin clots. Plasminogen activator activity also was not found in the suspension medium of frozen-thawed tumor cells, despite the fact that most of them had breaks on their cell membrane. Unlike freshly isolated tumor cells, PA was not released from frozen-thawed cells embedded in fibrin clots. Full PA activity was demonstrated in frozen-thawed cells treated with Triton X-100, however. Frozen-thawed cells exhibited signs of severe damage, and more than 80% of them failed to exclude trypan blue. Obviously PA is released from viable tumor cells embedded in fibrin clots but not suspended in artificial medium. The PA-release mechanism, not PA itself, is destroyed in cells rendered nonviable by freeze thawing. Images Figure 1 Figure 5 Figure 6 Figure 7 PMID:1902626

  3. The importance of behavior theory in control system modeling of physical activity sensor data.

    PubMed

    Riley, William T; Martin, Cesar A; Rivera, Daniel E

    2014-01-01

    Among health behaviors, physical activity has the most extensive record of research using passive sensors. Control systems and other system dynamic approaches have long been considered applicable for understanding human behavior, but only recently has the technology provided the precise and intensive longitudinal data required for these analytic approaches. Although sensors provide intensive data on the patterns and variations of physical activity over time, the influences of these variations are often unmeasured. Health behavior theories provide an explanatory framework of the putative mediators of physical activity changes. Incorporating the intensive longitudinal measurement of these theoretical constructs is critical to improving the fit of control system model of physical activity and for advancing behavioral theory. Theory-based control models also provide guidance on the nature of the controllers which serve as the basis for just-in-time adaptive interventions based on these control system models.

  4. Activity of Bifenthrin, Chlorfenapyr, Fipronil, and Thiamethoxam against Red Imported Fire Ants (Hymenoptera: Formicidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bifenthrin, chlorfenapyr, fipronil, and thiamethoxam were evaluated for activity against the Argentine ant, Linepithema humile (Mayr). Mobility impairment and lethal times were determined following topical treatments. Ants were immobilized most quickly by bifenthrin, followed by chlorfenapyr and thi...

  5. Structural transitions during prothrombin activation: On the importance of fragment 2

    PubMed Central

    Adams, Ty E.; Huntington, James A.

    2016-01-01

    Prothrombin is activated to thrombin by the prothrombinase complex through sequential cleavage at two distinct sites. This occurs at sites of vascular injury in a highly regulated cascade of serine protease and cofactor activation, where activated platelets provide a suitable surface for protease/cofactor/substrate assembly. The precise structural and conformational changes undergone during the transition from prothrombin to thrombin have been studied for decades, and several structures of prothrombin fragments along the activation pathway have been solved. Here we present a new structure analyzed in context of other recent structures and biochemical studies. What emerges is an unexpected mechanism that involves a change in the mode of binding of the F2 domain (fragment 2) on the catalytic domain after cleavage at Arg320, and a subsequent reorientation of the linker between the F2 and catalytic domain to present the Arg271 site for cleavage. PMID:26365066

  6. Chemical and biological mechanisms of phytochemical activation of Nrf2 and importance in disease prevention

    PubMed Central

    Eggler, Aimee L.; Savinov, Sergey N.

    2016-01-01

    Plants are an incredibly rich source of compounds that activate the Nrf2 transcription factor, leading to upregulation of a battery of cytoprotective genes. This perspective surveys established and proposed molecular mechanisms of Nrf2 activation by phytochemicals with a special emphasis on a common chemical property of Nrf2 activators: the ability as “soft” electrophiles to modify cellular thiols, either directly or as oxidized biotransformants. In addition, the role of reactive oxygen/nitrogen species as secondary messengers in Nrf2 activation is discussed. While the uniquely reactive C151 of Keap1, an Nrf2 repressor protein, is highlighted as a key target of cytoprotective phytochemicals, also reviewed are other stress-responsive proteins, including kinases, which play non-redundant roles in the activation of Nrf2 by plant-derived agents. Finally, the perspective presents two key factors accounting for the enhanced therapeutic windows of effective phytochemical activators of the Keap1–Nrf2 axis: enhanced selectivity toward sensor cysteines and reversibility of addition to thiolate molecules. PMID:26855455

  7. Studies on in vitro antioxidant and antistaphylococcal activities of some important medicinal plants.

    PubMed

    Mishra, A; Kumar, S; Bhargava, A; Sharma, B; Pandey, A K

    2011-02-12

    Oxidative stress is initiated by free radicals, which seek stability through electron pairing with biological macromolecules in healthy human cells and cause protein and DNA damage along with lipid peroxidation. Many phytochemicals have been found to play as potential antioxidants and antimicrobials. In the present study antioxidant and antistaphylococcal activities of Bauhinia variegata, Tinospora cardifolia and Piper longum have been determined. Total phenolic contents in plant extracts were estimated and different amounts of phenolic contents were found in B. variegata, T. cardifolia and P. longum extracts. The antioxidant activity of the extracts was compared with standard antioxidants such as, BHA, BHT, quercetin, ascorbic acid and propyl gallate. The % scavenging activity gradually increased with increasing concentrations of the test extracts in DPPH radical scavenging assay. Dose dependent antioxidant activity pattern was also observed in phosphomolybdate assay. Antioxidant activity was directly correlated with the amount of total phenolic contents in the extracts. As compared to B. variegata, the extracts from other two plants exhibited higher antioxidant activity. In disc diffusion assays several solvent extracts derived from test plants inhibited the growth of Staphylococcus aureus. Maximum inhibitory efficacy was observed in T. cardifolia extracts. However, the lowest minimum bactericidal concentration (MBC) (0.43 mg/ml) was recorded for ethyl acetate and acetone extracts of P. longum. This study demonstrates notable antioxidant and anti-staphylococcal roles assigned to some plant extracts tested.

  8. P38 activation is more important than ERK activation in lung injury induced by prolonged hyperbaric oxygen.

    PubMed

    Ma, Jun; Fang, Yi-Qun; Gu, Ai-Mei; Wang, Fang-Fang; Zhang, Shi; Li, Kai-Cheng

    2013-01-01

    Prolonged exposure to hyperbaric oxygen can cause pulmonary and nerve system toxicity. Although hyperbaric oxygen treatment has been used for a broad spectrum of ailments, the mechanisms of prolonged hyperbaric oxygen-induced lung injury are not fully understood. The purpose of the present work was to investigate the roles of ERK, p38, and caspase-3 in rat lung tissue exposed to hyperbaric oxygen at 2.3 atmospheres absolute (atm abs) for two, six and 10 hours. The results showed that the ERK and p38 were phosphorylated at two hours and reached a peak at six hours into exposure to hyperbaric oxygen. While the phosphorylation level of ERK decreased, p38 remained at a high level of activation at 10 hours. The activation of ERK and p38 was down-regulated when rats were exposed to normoxic hyperbaric nitrogen for 10 hours. However, caspase-3 was activated at six hours and 10 hours into exposure to hyperbaric oxygen. These results demonstrated different changes of activation of ERK and p38 during lung injury induced by prolonged exposure to hyperbaric oxygen. The time course changes of activated caspase-3 were similar to the process of p38 activation upon exposure to hyperbaric oxygen. In this way, activation of p38, not ERK, seems to be a mechanism associated with prolonged hyperbaric oxygen-induced lung injury.

  9. Glutamic acid-149 is important for enzymatic activity of yeast inorganic pyrophosphatase.

    PubMed

    Gonzalez, M A; Cooperman, B S

    1986-11-04

    Modification of Saccharomyces cerevisiae inorganic pyrophosphatase (PPase) with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide is known to lead to a loss of enzymatic activity, the rate of which is decreased in the presence of ligands binding to the active site [Cooperman, B. S., & Chiu, N. Y. (1973) Biochemistry 12, 1676-1682; Heitman, P., & Uhlig, H. J. (1974) Acta Biol. Med. Ger. 32, 565-594]. In this work we show that, when such inactivation is carried out in the presence of [14C]glycine ethyl ester (GEE), GEE is covalently incorporated into PPase, incorporation into the most highly labeled tryptic peptide is site-specific, as evidenced by the reduction of such incorporation in the presence of the active site ligands Zn2+ and Pi, the extent of formation of this specifically labeled peptide correlates with the fractional loss of PPase activity, and the specifically labeled peptide corresponds to residues 145-153 and the position of incorporation within this peptide is Glu-149. The significance of our findings for the location of the active site and for the catalytic mechanism of PPase is briefly considered in the light of the 3-A X-ray crystallographic structure of Arutyunyun and his colleagues [Arutyunyun, E. G., et al. (1981) Dokl. Akad. Nauk SSSR 258, 1481-1485; Kuranova, I. P., et al. (1983) Bioorg. Khim. 9, 1611-1919; Terzyan, S. S., et al. (1984) Bioorg. Khim. 10, 1469-1482].

  10. A Qualitative Study of Environmental Factors Important for Physical Activity in Rural Adults

    PubMed Central

    Cleland, Verity; Hughes, Clarissa; Thornton, Lukar; Venn, Alison; Squibb, Kathryn; Ball, Kylie

    2015-01-01

    Purpose Despite increasing evidence that the physical environment impacts on physical activity among urban-dwellers, little attention has been devoted to understanding this relationship in rural populations. Work in this area is further hindered by a lack of environmental measures specifically designed for rural settings. This qualitative study aimed to explore the salience of urban physical activity environment constructs among rural adults. Methods In 2011, 49 rural men and women from three distinct areas (coastal, animal-based farming, forestry/plant-based farming) of rural Tasmania, Australia, were purposively recruited to participate in semi-structured interviews. Interviews explored features of the built and social environment commonly examined in studies of urban adults, including functional characteristics (eg, lighting, footpaths, roads/verges), road and personal safety, availability and accessibility of places to be active, destinations, and aesthetics. Interviews were recorded, transcribed verbatim and analysed using a content-thematic approach using QSR NVivo software. Findings While some urban environmental constructs were salient to these rural adults, such as availability of and accessibility to places to be active, some constructs were operationalised differently, such as road safety (where large trucks and winding roads rather than traffic density was of concern), or were not considered relevant (eg, personal safety related to crime, availability of walkable destinations, aesthetics). Conclusions The measurement of the physical environment in rural populations may require reconsideration and/or modification to ensure salience and appropriate quantification of associations with physical activity in future studies. PMID:26554376

  11. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    PubMed Central

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  12. Pomegranate juice and prostate cancer: importance of the characterisation of the active principle.

    PubMed

    Chrubasik-Hausmann, Sigrun; Vlachojannis, Christian; Zimmermann, Benno

    2014-11-01

    Two exploratory clinical studies investigating proprietary pomegranate products showed a trend of effectiveness in increasing prostate-specific antigen doubling time in patients with prostate cancer. A recent clinical study did not support these results. We therefore analysed a lot of the marketed pomegranate blend for co-active pomegranate compounds. The high-performance liquid chromatography method was used to detect punicalagin, ellagic acid and anthocyanins. Total polyphenoles were determined by the Folin-Ciocalteu method using gallic acid as reference. The results show that the co-active compounds in the daily dose of the pomegranate blend were far below those previously tested and that the photometric assessment is not reliable for the standardisation of study medications. Not pomegranate but the low amount of co-active compounds in the proprietary pomegranate blend was responsible for its clinical ineffectiveness.

  13. Importance of Health-Related Fitness Knowledge to Increasing Physical Activity and Physical Fitness

    ERIC Educational Resources Information Center

    Ferkel, Rick C.; Judge, Lawrence W.; Stodden, David F.; Griffin, Kent

    2014-01-01

    Physical inactivity is expanding across all ages in the United States. Research has documented a deficiency in health-related fitness knowledge (HRFK) among elementary- through college-aged students. The need for a credible and reliable resource that provides research-based information regarding the importance of HRFK is significant. The purpose…

  14. 76 FR 50457 - Taking and Importing Marine Mammals; Military Training Activities and Research Conducted Within...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... National Oceanic and Atmospheric Administration RIN 0648-XA567 Taking and Importing Marine Mammals...: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of issuance of a Letter of Authorization. SUMMARY: In accordance with the Marine...

  15. 78 FR 36580 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Import/Export...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ...: Import/Export Declaration for List I and List II Chemicals; DEA Forms 486 and 486A ACTION: 30-Day Notice. The Department of Justice (DOJ), Drug Enforcement Administration (DEA) will be submitting the... Department sponsoring the collection: Form number: DEA Forms 486 and 486A. Component: Office of...

  16. 77 FR 47666 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Import/Export...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ...: Import/Export Declaration for List I and List II Chemicals; DEA Forms 486 and 486A ACTION: 60-Day Notice... Administration (DEA), will be submitting the following information collection request to the Office of Management... component of the Department of Justice sponsoring the collection: Form Number: DEA Forms 486 and...

  17. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    PubMed

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  18. Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity

    NASA Astrophysics Data System (ADS)

    Díaz-Urrutia, Christian A.; Olea-Azar, Claudio A.; Zapata, Gerald A.; Lapier, Michel; Mura, Francisco; Aguilera-Venegas, Benjamín; Arán, Vicente J.; López-Múñoz, Rodrigo A.; Maya, Juan D.

    A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.

  19. What is the importance of abnormal "background" activity in seizure generation?

    PubMed

    Staba, Richard J; Worrell, Gregory A

    2014-01-01

    Investigations of interictal epileptiform spikes and seizures have played a central role in the study of epilepsy. The background EEG activity, however, has received less attention. In this chapter we discuss the characteristic features of the background activity of the brain when individuals are at rest and awake (resting wake) and during sleep. The characteristic rhythms of the background EEG are presented, and the presence of 1/f (β) behavior of the EEG power spectral density is discussed and its possible origin and functional significance. The interictal EEG findings of focal epilepsy and the impact of interictal epileptiform spikes on cognition are also discussed.

  20. Importance of Quality Recreation Activities for Older Adults Residing in Nursing Homes: Considerations for Gerontologists.

    ERIC Educational Resources Information Center

    Haberkost, Michael; And Others

    1996-01-01

    Based on a needs assessment survey (66 responses from 101 nursing home activity coordinators), a recreation manual and training program was developed and tested with 25 coordinators/recreation staff. The 14 who completed evaluations increased their understanding of such topics as depression; goals of nursing home recreation programs; motivation of…

  1. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

    PubMed

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2014-01-01

    From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

  2. What Motives Are Important for Participation in Leisure-Time Activities at Swedish Youth Centres?

    ERIC Educational Resources Information Center

    Geidne, Susanna; Fredriksson, Ingela; Eriksson, Charli

    2016-01-01

    Objective: This study aimed to explore the motives of young people in multicultural suburbs for participating in youth-centre activities. Design and setting: The study employed practice-based research with a focus on collaboration and methodological diversity. Data on motives for participation were collected in spring 2013 at two non-governmental…

  3. Adolescents Online: The Importance of Internet Activity Choices to Salient Relationships

    ERIC Educational Resources Information Center

    Blais, Julie J.; Craig, Wendy M.; Pepler, Debra; Connolly, Jennifer

    2008-01-01

    The purpose of this study was to determine whether using the Internet for different activities affects the quality of close adolescent relationships (i.e., best friendships and romantic relationships). In a one-year longitudinal study of 884 adolescents (Mean age = 15, 46% male), we examined whether visiting chat rooms, using ICQ, using the…

  4. Student Perceptions of Information Literacy Instruction: The Importance of Active Learning

    ERIC Educational Resources Information Center

    Detlor, Brian; Booker, Lorne; Serenko, Alexander; Julien, Heidi

    2012-01-01

    This study investigates the merits of employing active learning strategies in the delivery of information literacy instruction (ILI). Traditional approaches to the teaching of information literacy skills--where students are passive recipients of the information they receive--are challenged. Rather, methods that encourage students to actively…

  5. Important Physiological Parameters and Physical Activity Data for Evaluating Exposure Modeling Performance: a Synthesis

    EPA Science Inventory

    The purpose of this report is to develop a database of physiological parameters needed for understanding and evaluating performance of the APEX and SHEDS exposure/intake dose rate model used by the Environmental Protection Agency (EPA) as part of its regulatory activities. The A...

  6. The importance of physical activity and sleep for affect on stressful days: Two intensive longitudinal studies.

    PubMed

    Flueckiger, Lavinia; Lieb, Roselind; Meyer, Andrea H; Witthauer, Cornelia; Mata, Jutta

    2016-06-01

    We investigated the potential stress-buffering effect of 3 health behaviors-physical activity, sleep quality, and snacking-on affect in the context of everyday life in young adults. In 2 intensive longitudinal studies with up to 65 assessment days over an entire academic year, students (Study 1, N = 292; Study 2, N = 304) reported stress intensity, sleep quality, physical activity, snacking, and positive and negative affect. Data were analyzed using multilevel regression analyses. Stress and positive affect were negatively associated; stress and negative affect were positively associated. The more physically active than usual a person was on a given day, the weaker the association between stress and positive affect (Study 1) and negative affect (Studies 1 and 2). The better than usual a person's sleep quality had been during the previous night, the weaker the association between stress and positive affect (Studies 1 and 2) and negative affect (Study 2). The association between daily stress and positive or negative affect did not differ as a function of daily snacking (Studies 1 and 2). On stressful days, increasing physical activity or ensuring high sleep quality may buffer adverse effects of stress on affect in young adults. These findings suggest potential targets for health-promotion and stress-prevention programs, which could help reduce the negative impact of stress in young adults. (PsycINFO Database Record

  7. Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death

    PubMed Central

    Morgan, Jessica A.; Lynch, John; Panetta, John C.; Wang, Yao; Frase, Sharon; Bao, Ju; Zheng, Jie; Opferman, Joseph T.; Janke, Laura; Green, Daniel M.; Chemaitilly, Wassim; Schuetz, John D.

    2015-01-01

    Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer. PMID:26576726

  8. Bling My Research! A Mock Grant Panel Activity Illustrating the Importance of Basic Research

    ERIC Educational Resources Information Center

    Leander, Celeste A.; Whitton, Jeannette

    2010-01-01

    First-year university students have misconceptions about the source and dynamics of publicly funded research money. We designed an activity in which students take part in a mock grant panel. The results indicated a strong tendency toward student funding of applied medical research at the expense of basic research. Exposure to a few examples of…

  9. Ambulatory Activity of Children with Cerebral Palsy: Which Characteristics Are Important?

    ERIC Educational Resources Information Center

    van Wely, Leontien; Becher, Jules G.; Balemans, Astrid C. J.; Dallmeijer, Annet J.

    2012-01-01

    Aim: To assess ambulatory activity of children with cerebral palsy (CP), aged 7 to 13 years, and identify associated characteristics. Method: Sixty-two children with spastic CP (39 males, 23 females; mean age 10y 1mo, SD 1y 8mo; age range 7-13y), classified as Gross Motor Function Classification System (GMFCS) levels I to III, participated.…

  10. Importance of Being Nernst: Synaptic Activity and Functional Relevance in Stem Cell-derived Neurons

    DTIC Science & Technology

    2015-07-26

    dissociated primary neurons, immortalized cell lines derived from neuronal and non-neuronal tissues and, most recently, stem cells. The predictive value of...repair of damaged neural tissues [8,9]. However, SCN models must be shown to be competent to form context-appropriate, functioning neurons before...of neuronal maturation have been well-described in dissociated cultures of primary neurons, it is important to recognize that the source tissues

  11. Translating active living research into policy and practice: one important pathway to chronic disease prevention.

    PubMed

    Giles-Corti, Billie; Sallis, James F; Sugiyama, Takemi; Frank, Lawrence D; Lowe, Melanie; Owen, Neville

    2015-05-01

    Global concerns about rising levels of chronic disease make timely translation of research into policy and practice a priority. There is a need to tackle common risk factors: tobacco use, unhealthy diets, physical inactivity, and harmful alcohol use. Using evidence to inform policy and practice is challenging, often hampered by a poor fit between academic research and the needs of policymakers and practitioners--notably for active living researchers whose objective is to increase population physical activity by changing the ways cities are designed and built. We propose 10 strategies that may facilitate translation of research into health-enhancing urban planning policy. Strategies include interdisciplinary research teams of policymakers and practitioners; undertaking explicitly policy-relevant research; adopting appropriate study designs and methodologies (evaluation of policy initiatives as 'natural experiments'); and adopting dissemination strategies that include knowledge brokers, advocates, and lobbyists. Conducting more policy-relevant research will require training for researchers as well as different rewards in academia.

  12. A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid ''Harmine''.

    PubMed

    Patel, K; Gadewar, M; Tripathi, R; Prasad, S K; Patel, Dinesh Kumar

    2012-08-01

    Harmine, a beta-carboline alkaloid, is widely distributed in the plants, marine creatures, insects, mammalians as well as in human tissues and body fluids. Harmine was originally isolated from seeds of Peganum harmal in 1847 having a core indole structure and a pyridine ring. Harmine has various types of pharmacological activities such as antimicrobial, antifungal, antitumor, cytotoxic, antiplasmodial, antioxidaant, antimutagenic, antigenotoxic and hallucinogenic properties. It acts on gamma-aminobutyric acid type A and monoamine oxidase A or B receptor, enhances insulin sensitivity and also produces vasorelaxant effect. Harmine prevents bone loss by suppressing osteoclastogenesis. The current review gives an overview on pharmacological activity and analytical techniques of harmine, which may be useful for researcheres to explore the hidden potential of harmine and and will also help in developing new drugs for the treatment of various diseases.

  13. Phase diagrams and water activities of aqueous dicarboxylic acid systems of atmospheric importance.

    PubMed

    Beyer, Keith D; Friesen, Katherine; Bothe, Jameson R; Palet, Benjamin

    2008-11-20

    We have studied liquid/solid phase diagrams and water activities of the dicarboxylic acid/water binary systems for maleic, dl-malic, glutaric, and succinc acids using differential scanning calorimetry, infrared (IR) spectroscopy of thin films, and conductivity analysis of saturated solutions. For each binary system we report the measurements of the ice melting envelope, the acid dissolution envelope, and the ice/acid eutectic temperature and composition. Water activities have been determined by using the freezing point depression of ice. Additionally, an irreversible solid/solid phase transition for maleic acid was observed in both DSC and IR studies likely due to the conversion of a meta-stable crystal form of maleic acid to its most stable crystal form. In general we find good agreement with literature values for temperature-dependent acid solubilities.

  14. Identification of nuclear import and export signals within Fli-1: roles of the nuclear import signals in Fli-1-dependent activation of megakaryocyte-specific promoters.

    PubMed

    Hu, Wei; Philips, Alana S; Kwok, Juliana C; Eisbacher, Michael; Chong, Beng H

    2005-04-01

    The Ets factor Friend leukemia integration 1 (Fli-1) is an important regulator of megakaryocytic (Mk) differentiation. Here, we demonstrate two novel nuclear localization signals (NLSs) within Fli-1: one (NLS1) is located at the N terminus, and another (NLS2) is within the Ets domain. Nuclear accumulation of Fli-1 reflected the combined functional effects of the two discrete NLSs. Each NLS can independently direct nuclear transport of a carrier protein, with mutations within the NLSs affecting nuclear accumulation. NLS1 has a bipartite motif, whereas the NLS2 region contains a nonclassical NLS. Both NLSs bind importin alpha (IMPalpha) and IMPbeta, with NLS1 and NLS2 being predominantly recognized by IMPalpha and IMPbeta, respectively. Fli-1 also contains one nuclear export signal. Leptomycin B abolished its cytoplasmic accumulation, showing CRM1 dependency. We demonstrate that Ets domain binding to specific target DNA effectively blocks IMP binding, indicating that the targeted DNA binding plays a role in localizing Fli-1 to its destination and releasing IMPs for recycling back to the cytoplasm. Finally, by analyzing full-length Fli-1 carrying NLS1, NLS2, and combined NLS1-NLS2 mutations, we conclude that two functional NLSs exist in Fli-1 and that each NLS is sufficient to target Fli-1 to the nucleus for activation of Mk-specific genes.

  15. Importance of the disulfide bridges in the antibacterial activity of human hepcidin.

    PubMed

    Hocquellet, Agnès; le Senechal, Caroline; Garbay, Bertrand

    2012-08-01

    Hepcidin was first identified as an antimicrobial peptide present in human serum and urine. It was later demonstrated that hepcidin is the long sought hormone that regulates iron homeostasis in mammals. The native peptide of 25 amino acids (Hepc25) contains four disulfide bridges that maintain a β-hairpin motif. The aim of the present study was to assess whether the intramolecular disulfide bridges are necessary for Hepc25 antimicrobial activity. We show that a synthetic peptide corresponding to human Hepc25, and which contains the four disulfide bridges, has an antibacterial activity against several strains of Gram-positive and Gram-negative bacteria. On the contrary, a synthetic peptide where all cysteines were replaced by alanines (Hepc25-Ala) had no detectable activity against the same strains of bacteria. In a further step, the mode of action of Hepc25 on Escherichia coli was studied. SYTOX Green uptake was used to assess bacterial membrane integrity. No permeabilization of the membrane was observed with Hepc25, indicating that this peptide does not kill bacteria by destroying their membranes. Gel retardation assay showed that the Hepc25 binds to DNA with high efficiency, and that this binding ability is dependent on the presence of the intramolecular disulfide bridges. Reduction of Hepc25 or replacement of the eight cysteines by alanine residues led to peptides that were no longer able to bind DNA in the in vitro assay. Altogether, these results demonstrate that Hepc25 should adopt a three-dimensional structure stabilized by the intramolecular disulfide bridges in order to have antibacterial activity.

  16. 75 FR 45527 - Taking and Importing Marine Mammals; Military Training Activities and Research, Development...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ...NMFS, upon application from the U.S. Navy (Navy) on behalf of the Department of Defense (including the Navy, the U.S. Air Force (USAF), and the U.S. Marine Corps (USMC)), is issuing regulations to govern the unintentional taking of marine mammals incidental to activities conducted in the Mariana Islands Range Complex (MIRC) study area for the period of July 2010 through July 2015. The Navy's......

  17. Importance of Membrane Structural Integrity for RPE65 Retinoid Isomerization Activity

    SciTech Connect

    Golczak, Marcin; Kiser, Philip D.; Lodowski, David T.; Maeda, Akiko; Palczewski, Krzysztof

    2010-04-05

    Regeneration of visual chromophore in the vertebrate visual cycle involves the retinal pigment epithelium-specific protein RPE65, the key enzyme catalyzing the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol. Although RPE65 has no predicted membrane spanning domains, this protein predominantly associates with microsomal fractions isolated from bovine retinal pigment epithelium (RPE). We have re-examined the nature of RPE65 interactions with native microsomal membranes by using extraction and phase separation experiments. We observe that hydrophobic interactions are the dominant forces that promote RPE65 association with these membranes. These results are consistent with the crystallographic model of RPE65, which features a large lipophilic surface that surrounds the entrance to the catalytic site of this enzyme and likely interacts with the hydrophobic core of the endoplasmic reticulum membrane. Moreover, we report a critical role for phospholipid membranes in preserving the retinoid isomerization activity and physical properties of RPE65. Isomerase activity measured in bovine RPE was highly sensitive to phospholipase A{sup 2} treatment, but the observed decline in 11-cis-retinol production did not directly reflect inhibition by products of lipid hydrolysis. Instead, a direct correlation between the kinetics of phospholipid hydrolysis and retinoid isomerization suggests that the lipid membrane structure is critical for RPE65 enzymatic activity. We also provide evidence that RPE65 operates in a multiprotein complex with retinol dehydrogenase 5 and retinal G protein-coupled receptor in RPE microsomes. Modifications in the phospholipid environment affecting interactions with these protein components may be responsible for the alterations in retinoid metabolism observed in phospholipid-depleted RPE microsomes. Thus, our results indicate that the enzymatic activity of native RPE65 strongly depends on its membrane binding and

  18. Graphene Oxide Catalyzed C-H Bond Activation: The Importance Oxygen Functional Groups for Biaryl Construction

    SciTech Connect

    Gao, Yongjun; Tang, Pei; Zhou, Hu; Zhang, Wei; Yang, Hanjun; Yan, Ning; Hu, Gang; Mei, Donghai; Wang, Jianguo; Ma, Ding

    2016-02-24

    A heterogeneous, inexpensive and environment-friendly carbon catalytic system was developed for the C-H bond arylation of benzene resulting in the subsequent formation of biaryl compounds. The oxygen-containing groups on these graphene oxide sheets play an essential role in the observed catalytic activity. The catalytic results of model compounds and DFT calculations show that these functional groups promote this reaction by stabilization and activation of K ions at the same time of facilitating the leaving of I. And further mechanisms studies show that it is the charge induced capabilities of oxygen groups connected to specific carbon skeleton together with the giant π-reaction platform provided by the π-domain of graphene that played the vital roles in the observed excellent catalytic activity. D. Mei acknowledges the support from the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory.

  19. Maintaining network activity in submerged hippocampal slices: importance of oxygen supply.

    PubMed

    Hájos, Norbert; Ellender, Tommas J; Zemankovics, Rita; Mann, Edward O; Exley, Richard; Cragg, Stephanie J; Freund, Tamás F; Paulsen, Ole

    2009-01-01

    Studies in brain slices have provided a wealth of data on the basic features of neurons and synapses. In the intact brain, these properties may be strongly influenced by ongoing network activity. Although physiologically realistic patterns of network activity have been successfully induced in brain slices maintained in interface-type recording chambers, they have been harder to obtain in submerged-type chambers, which offer significant experimental advantages, including fast exchange of pharmacological agents, visually guided patch-clamp recordings, and imaging techniques. Here, we investigated conditions for the emergence of network oscillations in submerged slices prepared from the hippocampus of rats and mice. We found that the local oxygen level is critical for generation and propagation of both spontaneously occurring sharp wave-ripple oscillations and cholinergically induced fast oscillations. We suggest three ways to improve the oxygen supply to slices under submerged conditions: (i) optimizing chamber design for laminar flow of superfusion fluid; (ii) increasing the flow rate of superfusion fluid; and (iii) superfusing both surfaces of the slice. These improvements to the recording conditions enable detailed studies of neurons under more realistic conditions of network activity, which are essential for a better understanding of neuronal network operation.

  20. Antifungal activity of different neem leaf extracts and the nimonol against some important human pathogens

    PubMed Central

    Mahmoud, D.A.; Hassanein, N.M.; Youssef, K.A.; Abou Zeid, M.A.

    2011-01-01

    This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15 and 20%) prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC) analysis of ethyl acetate extract showed the presence of a main component (nimonol) which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens. PMID:24031718

  1. The importance of cyclic structure for Labaditin on its antimicrobial activity against Staphylococcus aureus.

    PubMed

    Barbosa, Simone C; Nobre, Thatyane M; Volpati, Diogo; Ciancaglini, Pietro; Cilli, Eduardo M; Lorenzón, Esteban N; Oliveira, Osvaldo N

    2016-12-01

    Antimicrobial resistance has reached alarming levels in many countries, thus leading to a search for new classes of antibiotics, such as antimicrobial peptides whose activity is exerted by interacting specifically with the microorganism membrane. In this study, we investigate the molecular-level mechanism of action for Labaditin (Lo), a 10-amino acid residue cyclic peptide from Jatropha multifida with known bactericidal activity against Streptococcus mutans. We show that Lo is also effective against Staphylococcus aureus (S. aureus) but this does not apply to its linear analogue (L1). Using polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), we observed with that the secondary structure of Lo was preserved upon interacting with Langmuir monolayers from a phospholipid mixture mimicking S. aureus membrane, in contrast to L1. This structure preservation for the rigid, cyclic Lo is key for the self-assembly of peptide nanotubes that induce pore formation in large unilamellar vesicles (LUVs), according to permeability assays and dynamic light scattering measurements. In summary, the comparison between Labaditin (Lo) and its linear analogue L1 allowed us to infer that the bactericidal activity of Lo is more related to its interaction with the membrane. It does not require specific metabolic targets, which makes cyclic peptides promising for antibiotics without bacteria resistance.

  2. Monitoring of disease biomarkers activity and immunophenotyping as important factors in SLE clinical management.

    PubMed

    Subasic, Djemo; Karamehic, Jasenko; Delic-Sarac, Marina; Kasumovic, Mersija; Mekic, Mevludin; Eminovic, Izet; Hasanagic, Nermina

    2012-01-01

    The highly specific biomarkers for monitoring of SLE disease activity are not yet defined up to date, due to existing of different clinical SLE phenotypes caused by individual genetic variation. Basically, numerous clinical complications follow SLE patients such as nephritis, atherosclerosis and cardial, CNS, gastrointestinal and ophthalmological complications, as well. Their monitoring in clinical SLE management can be evaluated by analysing of specific biochemical parameters and require permanent clinical observation. The presence of ANAs and anti-ds-DNAs are usual diagnostic SLE autoimmunity parameters, while SLE disease activity biomarkers are C3 and C4 level, anticardiolipin antibodies, anti-Sm/RNPs and, recently level of CD4 and CD8 lymphocytes. However, the number of TCR molecules on the T-cells surface at SLE patients is lower then in normal condition, and otherwise for these receptors CD molecules make specific connection. On the other hand, the T lymphocytes can be also, therapeutical targets at SLE patients, because of their clear direct involving in SLE pathogenesis. The SLE phenotypes are characterized by double CD negativity ( CD3 +/-, CD4-) caused by abnormal level of IL-2 and IL-17. T-lymphocytes have usually alpha-beta and gamma-delta TCR receptors, but for SLE patients is characteristic lower number gama-delta TCR molecules, detected in the peripheral blood specimens. Taking into account all of the facts, we investigated the level of specific usual SLE activity biomarkers (anti-ds-DNAs, C3, C4, anticardiolipin antibodies (beta-2-IgG, beta-2-IgM, ACA-G, ACA-M, CD4 and CD8 level) in serum specimens of SLE patients who underwent to the corresponding chemotherapy in combination with other biochemical and clinical parameters. Once again proved to be, that SLE biomarker monitoring, could be useful aproach for SLE activity disease and prediction organ damage, as well. In our investigation we used the following methods: immunofluorescence microscopy (IFA

  3. Are Parental Perceptions of Child Activity Levels and Overall Health More Important than Perceptions of Weight?

    PubMed Central

    Vangeepuram, Nita; Ramos, Michelle A.; Fei, Kezhen; Fox, Ashley M.; Horowitz, Carol R.; Kleinman, Lawrence C.; Galvez, Maida P.

    2016-01-01

    Objectives To examine relationships between parental perceptions of child weight and overall health, reported lifestyle behaviors and measured body mass index (BMI). Methods Using community-partnered methods, we surveyed families residing in a two census tract area identified for targeted interventions to decrease diabetes related disparities. The survey included demographics, child dietary and physical activity behaviors, and parental perception of child’s health and weight. We measured child BMI using a standardized protocol. Results We surveyed parents of 116 children with a mean age of 7 years (range 3–15) with 51 % boys, 74 % Hispanic, and 26 % Black. Over half of the children (55 %) were overweight or obese. Half (50 %) of the parents underestimated their children’s weight. Reported daily hours of walking and/or running trended higher (3.6 vs. 2.6 h, p = 0.08) for children perceived to be of normal weight. Parents who correctly estimated their child’s weight status reported more hours of daily walking/running than parents who underestimated child weight status, 4.5 versus 2.4 h, p = 0.0002. Parents of healthy weight children were more likely to report that children were in excellent or very good health compared to parents of overweight/obese children, 75 versus 56 % respectively (p = 0.04). We found significant racial/ethnic differences in reported diet and physical activity behaviors and perception of overall health. Conclusions for Practice Parental perceptions of child health and physical activity level may be related to perceptions of their child’s weight status. Study findings informed community-based initiatives for reducing diabetes risk among children. PMID:27010551

  4. SUMO-Interacting Motifs of Human TRIM5α are Important for Antiviral Activity

    PubMed Central

    Goff, Stephen P.

    2011-01-01

    Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA. PMID:21490953

  5. [Importance and evidence of regular physical activity for prevention and treatment of diseases].

    PubMed

    Löllgen, H

    2013-10-01

    A sedentary lifestyle has been shown to have negative effects on morbidity and mortality. In contrast, a large number of prospective cohort studies on the effects of regular physical activity demonstrated positive effects. Therefore, physical training is today an essential part of prevention and therapy in internal medicine. This review is based on literature research in meta-analysis and review papers. Regular physical exercise or training is a significant and evidence-based part of prevention and therapy of diseases such as heart, cardiovascular and lung diseases, diabetes mellitus, renal disease and cancer. Evidence of training effects is mostly high grade. Physical activity or exercise training is indicated in many diseases as medicine--similar as a drug. It is applied after acute treatment as a component of the standard drug therapy. There is a non-linear dose-response effect, psychological aspects and some side-effects need to be considered.In conclusion, physical exercise acts as a highly efficient drug, and should be used in many diseases. Training recommendations refer to the kind, the duration, the intensity, the frequency and the increase of training.

  6. Activity of leucine aminopeptidase of Telchin licus licus: an important insect pest of sugarcane.

    PubMed

    Valencia, Jorge W Arboleda; de Sá, Maria Fátima Grossi; Jiménez, Arnubio Valencia

    2014-06-01

    The enzymatic activity of leucine aminopeptidase (EC 3.4.11.1) from the intestinal tract of sugarcane giant borer (Telchin licus licus) was assayed by using a simple and sensitive spectrophotometric assay that uses L-leucyl-2- naphthylamide as substrate. In this assay, L-leucyl-2-naphthylamide is hydrolyzed to produce 2-naphthylamine and Lleucine. The product 2-naphthylamine reacts with Fast Black K and can be monitored using a continuous spectrophotometric measurement at 590 nm. The data on the kinetic parameters indicates that the Km for the L-leucyl-2- naphthylamide at pH 7.0 was found to be lower than those found for other LAP substrates. The Km and Vmax for the LAP were determined to be 84.03 µM and 357.14 enzymatic units mg(-1), respectively. A noticeable difference of LAP activity between the two insect orders tested was observed. This method could be used to screen for natural LAP inhibitors.

  7. Importance of backbone angles versus amino acid configurations in peptide vibrational Raman optical activity spectra

    NASA Astrophysics Data System (ADS)

    Herrmann, Carmen; Ruud, Kenneth; Reiher, Markus

    2008-01-01

    In this work, we investigate whether the differential scattering of right- and left-circularly polarized light in peptide Raman optical activity spectra are uniquely dominated by the backbone conformation, or whether the configurations of the individual amino acid also play a significant role. This is achieved by calculating Raman optical activity spectra using density functional theory for four structurally related peptides with a common backbone conformation, but with different sequences of amino acid configurations. Furthermore, the ROA signals of the amide normal modes are decomposed into contributions from groups of individual atoms. It is found that the amino acid configuration has a considerable influence on the ROA peaks in the amide I, II, and III regions, although the local decomposition reveals that the side-chain atoms only contribute to those peaks directly in the case of the amide II vibrations. Furthermore, small changes in the amide normal modes may lead to large and irregular modifications in the ROA intensity differences, making it difficult to establish transferable ROA intensity differences even for structurally similar vibrations.

  8. Critical importance of stimulus unawareness for the production of subliminal psychodynamic activation effects. An attributional model.

    PubMed

    Bornstein, R F

    1992-02-01

    This paper describes a new theoretical model of subliminal psychodynamic activation (SPA) effects. The model conceptualizes subliminal-supraliminal differences in SPA effects as being due to differences in subjects' attributions for the changes in anxiety level that are produced by subliminal versus supraliminal SPA stimuli. Changes in anxiety level produced by supraliminal SPA stimuli can be attributed by subjects to the experimental procedures, diminishing the impact of these messages on subjects' responses. In contrast, subjects cannot attribute changes in anxiety level produced by subliminal SPA stimuli to the experimental procedures. Therefore, no "discounting" (i.e., situational) attributions for subliminally induced changes in anxiety levels are available to subjects, and subliminal SPA messages produce significantly stronger effects on responding than do supraliminal SPA messages. The attributional model of SPA effects is discussed in the context of other long-term research programs investigating subliminal phenomena. The implications of this model for clinical treatment and empirical research utilizing the SPA paradigm are discussed.

  9. Lymphocyte-activation gene-3, an important immune checkpoint in cancer.

    PubMed

    He, Yayi; Rivard, Christopher J; Rozeboom, Leslie; Yu, Hui; Ellison, Kim; Kowalewski, Ashley; Zhou, Caicun; Hirsch, Fred R

    2016-09-01

    Immunotherapy has recently become widely used in lung cancer. Many oncologists are focused on cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1). Immunotherapy targeting the PD-1/PD-L1 checkpoints has shown promising efficacy in non-small cell lung cancer (NSCLC), but questions remain to be answered. Among them is whether the simultaneous inhibition of other checkpoints could improve outcomes. Lymphocyte-activation gene-3 (LAG-3) is another vital checkpoint that may have a synergistic interaction with PD-1/PD-L1. Here we review the LAG-3 function in cancer, clinical trials with agents targeting LAG-3 and the correlation of LAG-3 with other checkpoints.

  10. Studies of neutron cross-sections important for spallation experiments using the activation method

    NASA Astrophysics Data System (ADS)

    Vrzalová, J.; Chudoba, P.; Krása, A.; Majerle, M.; Suchopár, M.; Svoboda, O.; Wagner, V.

    2014-09-01

    A series of experiments devoted to studies of neutron cross-sections by activation method was carried out. The cross-sections of various threshold reactions were studied by means of different quasi-monoenergetic neutron sources with energies from 14 MeV up to 100 MeV. Threshold reactions in various materials are among other used to measure fast neutron fields produced during accelerator driven system studies. For this reason our measurements of neutron cross-sections are crucial. At present, neither experimental nor evaluated data above 30 MeV are available for neutron threshold reactions in Au, I and In published in this proceedings. We studied materials in the form of thin foils and compared our data with the calculations preformed using the deterministic code TALYS 1.4.

  11. Is anterior cruciate ligament surgery technique important in rehabilitation and activity scores?

    PubMed Central

    Kilinc, Bekir Eray; Kara, Adnan; Celik, Haluk; Oc, Yunus; Camur, Savas

    2016-01-01

    To compare the two different anterior cruciate ligament surgery techniques’ effect in rehabilitation and activity performance. Fifty-five patients were evaluated. Twenty-seven patients with transtibial technique (TT), 28 with anatomic single-bundle technique (AT) included. Tegner Activity Scale (TAS) was performed at preoperation and follow-up. The returning time of the sport and work was evaluated at follow-up. Single-leg hop test was performed at follow-up. Outcomes were compared between the two groups. The determined length difference between the operated knee and the intact knee was compared between the two groups. Average age of TT and AT was 27.9±6.4 yr, 28.3±6 yr, respectively. There was a significant difference between the two groups in duration of returning to sport. TT group had higher duration to return to sport (P<0.01). No difference between the two groups in duration of returning to work (P>0.05). There was a significant difference between the two groups. TT group had significantly higher values than AT group (P<0.01). No difference in TAS between the two techniques at preoperation and at last follow-up (P>0.05). The increase of TAS in patients who had AT was higher than the patients who had TT (P>0.05). No difference in single-leg hop test at 55%–65%, 65%–75%, and 85%–95% level (P>0.05). In this test at 75%–85% TT group had higher values than AT group (P<0.05), AT group had higher values at 95%–105% level (P<0.05). Good short and long-term knee outcome scores depend on rehabilitation protocol after surgery. Surgery technique should provide the adequate stability in rehabilitation period. AT obtains better outcomes in rehabilitation. PMID:27419120

  12. Dual Sensory Loss and Depressive Symptoms: The Importance of Hearing, Daily Functioning, and Activity Engagement

    PubMed Central

    Kiely, Kim M.; Anstey, Kaarin J.; Luszcz, Mary A.

    2013-01-01

    Background: The association between dual sensory loss (DSL) and mental health has been well established. However, most studies have relied on self-report data and lacked measures that would enable researchers to examine causal pathways between DSL and depression. This study seeks to extend this research by examining the effects of DSL on mental health, and identify factors that explain the longitudinal associations between sensory loss and depressive symptoms. Methods: Piecewise linear-mixed models were used to analyze 16-years of longitudinal data collected on up to five occasions from 1611 adults (51% men) aged between 65 and 103 years. Depressive symptoms were assessed by the Centre for Epidemiological Studies Depression (CES-D). Vision loss (VL) was defined by corrected visual acuity >0.3 logMAR in the better eye, blindness, or glaucoma. Hearing loss (HL) was defined by pure-tone average (PTA) >25 dB in the better hearing ear. Analyses were adjusted for socio-demographics, medical conditions, lifestyle behaviors, activities of daily living (ADLs), cognitive function, and social engagement. Results: Unadjusted models indicated that higher levels of depressive symptoms were associated with HL (B = 1.16, SE = 0.33) and DSL (B = 2.15, SE = 0.39) but not VL. Greater rates of change in depressive symptoms were also evident after the onset of HL (B = 0.16, SE = 0.06, p < 0.01) and DSL (B = 0.30, SE = 0.09, p < 0.01). The associations between depressive symptoms and sensory loss were explained by difficulties with ADLs, and social engagement. Conclusion: Vision and HL are highly prevalent among older adults and their co-occurrence may compound their respective impacts on health, functioning, and activity engagement, thereby exerting strong effects on the mental health and wellbeing of those affected. There is therefore a need for rehabilitation programs to be sensitive to the combined effects of sensory loss on individuals

  13. The Effects of Constraint-Induced Movement Therapy on Activities Important to Independent School Participation of Children with Hemiparesis

    ERIC Educational Resources Information Center

    Carney, Joan

    2012-01-01

    This study investigated the efficacy of constraint-induced movement therapy (CI therapy) on activities important to school participation in children with hemiparesis. Four children, ages 4-0 to 7-10 participated in an intensive CI therapy program in a clinical setting. Constraining casts were worn 24 hours daily. Therapy was delivered 6 hours…

  14. Integrity of N- and C-termini is important for E. coli Hsp31 chaperone activity.

    PubMed

    Sastry, M S R; Zhou, Weibin; Baneyx, François

    2009-07-01

    Hsp31 is a stress-inducible molecular chaperone involved in the management of protein misfolding at high temperatures and in the development of acid resistance in starved E. coli. Each subunit of the Hsp31 homodimer consists of two structural domains connected by a flexible linker that sits atop a continuous tract of nonpolar residues adjacent to a hydrophobic bowl defined by the dimerization interface. Previously, we proposed that while the bowl serves as a binding site for partially folded species at physiological temperatures, chaperone function under heat shock conditions requires that folding intermediates further anneal to high-affinity binding sites that become uncovered upon thermally induced motion of the linker. In support of a mechanism requiring that client proteins first bind to the bowl, we show here that fusion of a 20-residue-long hexahistidine tag to the N-termini of Hsp31 abolishes chaperone activity at all temperatures by inducing reversible structural changes that interfere with substrate binding. We further demonstrate that extending the C-termini of Hsp31 with short His tags selectively suppresses chaperone function at high temperatures by interfering with linker movement. The structural and functional sensitivity of Hsp31 to lengthening is consistent with the high degree of conservation of class I Hsp31 orthologs and will serve as a cautionary tale on the implications of affinity tagging.

  15. Evaluation of antioxidant and anticancer activity of copper oxide nanoparticles synthesized using medicinally important plant extracts.

    PubMed

    Rehana, Dilaveez; Mahendiran, D; Kumar, R Senthil; Rahiman, A Kalilur

    2017-03-10

    Copper oxide (CuO) nanoparticles were synthesized by green chemistry approach using different plant extracts obtained from the leaves of Azadirachta indica, Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera and Tamarindus indica. In order to compare their efficiency, the same copper oxide nanoparticles was also synthesized by chemical method. Phytochemical screening of the leaf extracts showed the presence of carbohydrates, flavonoids, glycosides, phenolic compounds, saponins, tannins, proteins and amino acids. FT IR spectra confirmed the possible biomolecules responsible for the formation of copper oxide nanoparticles. The surface plasmon resonance absorption band at 220-235nm in the UV-vis spectra also supports the formation of copper oxide nanoparticles. XRD patterns revealed the monoclinic phase of the synthesized copper oxide nanoparticles. The average size, shape and the crystalline nature of the nanoparticles were determined by SEM, TEM and SAED analysis. EDX analysis confirmed the presence of elements in the synthesized nanoparticles. The antioxidant activity was evaluated by three different free radical scavenging assays. The cytotoxicity of copper oxide nanoparticles was evaluated against four cancer cell lines such as human breast (MCF-7), cervical (HeLa), epithelioma (Hep-2) and lung (A549), and one normal human dermal fibroblast (NHDF) cell line. The morphological changes were evaluated using Hoechst 33258 staining assay. Copper oxide nanoparticles synthesized by green method exhibited high antioxidant and cytotoxicity than that synthesized by chemical method.

  16. The Importance of Vibronic Coupling for Efficient Reverse Intersystem Crossing in Thermally Activated Delayed Fluorescence Molecules

    PubMed Central

    Gibson, Jamie; Monkman, Andrew P.

    2016-01-01

    Abstract Factors influencing the rate of reverse intersystem crossing (k rISC) in thermally activated delayed fluorescence (TADF) emitters are critical for improving the efficiency and performance of third‐generation heavy‐metal‐free organic light‐emitting diodes (OLEDs). However, present understanding of the TADF mechanism does not extend far beyond a thermal equilibrium between the lowest singlet and triplet states and consequently research has focused almost exclusively on the energy gap between these two states. Herein, we use a model spin‐vibronic Hamiltonian to reveal the crucial role of non‐Born‐Oppenheimer effects in determining k rISC. We demonstrate that vibronic (nonadiabatic) coupling between the lowest local excitation triplet (3LE) and lowest charge transfer triplet (3CT) opens the possibility for significant second‐order coupling effects and increases k rISC by about four orders of magnitude. Crucially, these simulations reveal the dynamical mechanism for highly efficient TADF and opens design routes that go beyond the Born‐Oppenheimer approximation for the future development of high‐performing systems. PMID:27338655

  17. Active processes on a mixed clastic carbonate Brazilian shelf margin: Importance for hydrocarbon exploration in turbidites

    SciTech Connect

    Cainelli, C. )

    1991-03-01

    The search for subtle hydrocarbon accumulations in turbidite systems requires additional approaches for more successful exploration, particularly when direct recognition on seismic lines is difficult. This includes the determination and understanding of processes controlling sand distribution on the shelf and the mapping of sand pathways from the shelf to the slop/basin that can guide efforts to look for more favorable sites for turbidite sandstone deposition. The approach can be exemplified in the Sergipe-Alagoas basin, on the Brazillian Atlantic passive margin. The section analyzed is the Piacabucu Formation, a thick seaward prograding wedge composed of coastal sandstones and shelf edge carbonates on a narrow shelf and slope-basin shales with turbidite lenses. Waves and currents control the redistribution of sediments transported to the shelf by rivers. More wave energy is expended in ten hours in the San Francisco delta than in an entire year in the Mississippi delta. Such environment precludes deposition of mud on the shelf, but it stimulates the development of shelf edge carbonates. Rimed carbonates along the shelf break serve as a barrier for downslope movements of coarse-grained sediment, where turbidites are oil targets. The search for gaps in the carbonate barrier which can tap the behind-barrier sands is critical for sand-rich turbidite development. It is believed that canyons create these gaps and act as active turbidity current routes.

  18. Structure-activity relationships of nonisomerizable derivatives of tamoxifen: importance of hydroxyl group and side chain positioning for biological activity.

    PubMed

    Murphy, C S; Parker, C J; McCague, R; Jordan, V C

    1991-03-01

    The antiestrogen tamoxifen [(Z)-1(p-beta-dimethylaminoethoxy-phenyl)-1,2-diphenylbut-1-ene] is an effective anticancer agent against estrogen receptor (ER)-positive breast cancer. The alkylaminoethane side chain is essential for antiestrogenic activity, but the potency of the antiestrogen can be increased by para hydroxylation of the phenyl ring on carbon 1 of but-1-ene. This compound, 4-hydroxytamoxifen, is a metabolite of tamoxifen and has a very high binding affinity for ER [J. Endocrinol. 75:305-316 (1977)] because the hydroxyl is located in the equivalent position as the 3-phenolic hydroxyl of 17 beta-estradiol. In this study, we have examined the relationship between the relative positions of the hydroxyl and the alkyl-aminoethane side chain and the pharmacological activity of the ligand. A fixed seven-membered ring derivative of the triphenylethylene was used to prevent isomerization. All compounds were tested, with and without 17 beta-estradiol, for their effects on the growth of estrogen-responsive T47D and MCF-7 human breast cancer cells in vitro. The growth of MDA-MB-231 ER-negative breast cancer cells was not affected by any of the compounds tested, at a concentration (1 microM) that had a profound estrogenic or antiestrogenic action in ER-positive cell lines. The relative binding affinity of the compounds was determined using rat uterine ER and was found to be consistent with the observed potencies in vitro. The compounds found to be antiestrogens in vitro were antiestrogenic against estradiol (0.08 micrograms daily) in the 3-day immature rat uterine weight test. All compounds were partial agonists in vivo. In general, the estrogenic and antiestrogenic results obtained in vivo were consistent with the potency estimates obtained with the breast cancer cells in vitro. The results of this extensive structure-activity relationship study demonstrate that the substitution for 4-hydroxytamoxifen appears to be optimal to produce a potent antiestrogen; all

  19. The importance of methanotrophic activity in geothermal soils of Pantelleria island (Italy)

    NASA Astrophysics Data System (ADS)

    D'Alessandro, Walter; Gagliano, Antonina Lisa; Quatrini, Paola; Parello, Francesco

    2013-04-01

    Methane is a major contributor to the greenhouse effect, its atmospheric concentration being more than doubled since the XIX century. Every year 22 Tg of methane are released to the atmosphere from several natural and anthropogenic sources. Natural sources include geothermal/volcanic areas but the estimation of the total methane emission from these areas is currently not well defined since the balance between emission through degassing and microbial oxidation within the soils is not well known. Microbial oxidation in soils contributes globally for about 3-9% to the removal of methane from the atmosphere and recent studies evidenced methanotrophic activity also in soils of volcanic/geothermal areas despite their harsh environmental conditions (high temperatures, low pH and high concentrations of H2S and NH3). Methanotrophs are a diverse group of bacteria that are able to metabolize methane as their only source of carbon and energy and are found within the Alpha and Gamma classes of Proteobacteria and within the phylum Verrucomicrobia. Our purpose was to study the interaction between methanotrophic communities and the methane emitted from the geothermally most active site of Pantelleria island (Italy), Favara Grande, whose total methane emission has been previously estimated in about 2.5 t/a. Laboratory incubation experiments with soil samples from Favara Grande showed methane consumption values of up to 9500 ng g-1 dry soil per hour while soils collected outside the geothermal area consume less than 6 ng g-1 h-1. The maximum consumption was measured in the shallowest part of the soil profile (1-3 cm) and high values (>100 ng g-1 h-1) were maintained up to a depht of 15 cm. Furthermore, the highest consumption was measured at 37°C, and a still recognizable consumption (>20 ng g-1 h-1) at 80°C, with positive correlation with the methane concentration in the incubation atmosphere. These results can be considered a clear evidence of the presence of methanotrophs that

  20. An in vivo assessment of muscular activity and the importance of electrical phenomena in bone remodelling.

    PubMed Central

    McDonald, F; Houston, W J

    1990-01-01

    Modified orthopaedic pins were placed close to the medial and distal epiphyses of the tibia in 4 anaesthetised rabbits, in order to allow the application of controlled external loading cycles. Rosette strain gauges were placed at midshaft level, where the greatest compressive and tensile strains were expected during loading. Two weeks later, following stabilisation of the pins by bone healing, the animals were anaesthetised again and silver-silver chloride electrodes were attached close to the strain gauges in order to measure the changes in electrical potential difference. A sinusoidal load cycle was exerted between the pins with peak levels of 100 N or 250 N depending on the age of the animal. A fluctuation in potential difference, in synchrony with the strain recorded by the strain gauges, was recorded. The maximum potential difference was 2.2 mV, and it was not possible to exceed this with increased bone strain. After demonstration of the piezoelectric effect, repeated stimuli were applied to the sciatic nerve, producing a twitch in the muscles adjacent to the tibia. The electric potential difference from the muscles completely overwhelmed the local potential difference at the bone surface. A further two animals were prepared as previously described, and one electrode was placed on the endosteal surface. The electrical events mirror the changes found across the limb. The stimulus to bone remodeling, as distinct from growth, is usually loading in association with muscular activity. The fact that the changes in electrical fields at the bone surface are predominantly those originating in the muscles indicates that local electrical phenomena generated by bone strain cannot be the factors initiating the cellular response that is responsible for bone remodeling. Images Fig. 1 PMID:2272901

  1. Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  2. Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy.

    PubMed

    Shamshiri, Elhum A; Tierney, Tim M; Centeno, Maria; St Pier, Kelly; Pressler, Ronit M; Sharp, David J; Perani, Suejen; Cross, J Helen; Carmichael, David W

    2017-01-01

    Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG-fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told "please wait") was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brain's functional organisation. Hum Brain Mapp 38:221-236, 2017. © 2016 Wiley Periodicals, Inc.

  3. Estimation of effective doses to adult and pediatric patients from multislice computed tomography: A method based on energy imparted

    SciTech Connect

    Theocharopoulos, Nicholas; Damilakis, John; Perisinakis, Kostas; Tzedakis, Antonis; Karantanas, Apostolos; Gourtsoyiannis, Nicholas

    2006-10-15

    The purpose of this study is to provide a method and required data for the estimation of effective dose (E) values to adult and pediatric patients from computed tomography (CT) scans of the head, chest abdomen, and pelvis, performed on multi-slice scanners. Mean section radiation dose (d{sub m}) to cylindrical water phantoms of varying radius normalized over CT dose index free-in-air (CTDI{sub F}) were calculated for the head and body scanning modes of a multislice scanner with use of Monte Carlo techniques. Patients were modeled as equivalent water phantoms and the energy imparted ({epsilon}) to simulated pediatric and adult patients was calculated on the basis of measured CTDI{sub F} values. Body region specific energy imparted to effective dose conversion coefficients (E/{epsilon}) for adult male and female patients were generated from previous data. Effective doses to patients aged newborn to adult were derived for all available helical and axial beam collimations, taking into account age specific patient mass and scanning length. Depending on high voltage, body region, and patient sex, E/{epsilon} values ranged from 0.008 mSv/mJ for head scans to 0.024 mSv/mJ for chest scans. When scanned with the same technique factors as the adults, pediatric patients absorb as little as 5% of the energy imparted to adults, but corresponding effective dose values are up to a factor of 1.6 higher. On average, pediatric patients absorb 44% less energy per examination but have a 24% higher effective dose, compared with adults. In clinical practice, effective dose values to pediatric patients are 2.5 to 10 times lower than in adults due to the adaptation of tube current. A method is provided for the calculation of effective dose to adult and pediatric patients on the basis of individual patient characteristics such as sex, mass, dimensions, and density of imaged anatomy, and the technical features of modern multislice scanners. It allows the optimum selection of scanning

  4. Balance of activities of alcohol acetyltransferase and esterase in Saccharomyces cerevisiae is important for production of isoamyl acetate.

    PubMed

    Fukuda, K; Yamamoto, N; Kiyokawa, Y; Yanagiuchi, T; Wakai, Y; Kitamoto, K; Inoue, Y; Kimura, A

    1998-10-01

    Isoamyl acetate is synthesized from isoamyl alcohol and acetyl coenzyme A by alcohol acetyltransferase (AATFase) in Saccharomyces cerevisiae and is hydrolyzed by esterases at the same time. We hypothesized that the balance of both enzyme activities was important for optimum production of isoamyl acetate in sake brewing. To test this hypothesis, we constructed yeast strains with different numbers of copies of the AATFase gene (ATF1) and the isoamyl acetate-hydrolyzing esterase gene (IAH1) and used these strains in small-scale sake brewing. Fermentation profiles as well as components of the resulting sake were largely alike; however, the amount of isoamyl acetate in the sake increased with an increasing ratio of AATFase/Iah1p esterase activity. Therefore, we conclude that the balance of these two enzyme activities is important for isoamyl acetate accumulation in sake mash.

  5. Balance of Activities of Alcohol Acetyltransferase and Esterase in Saccharomyces cerevisiae Is Important for Production of Isoamyl Acetate

    PubMed Central

    Fukuda, Kiyoshi; Yamamoto, Nagi; Kiyokawa, Yoshifumi; Yanagiuchi, Toshiyasu; Wakai, Yoshinori; Kitamoto, Katsuhiko; Inoue, Yoshiharu; Kimura, Akira

    1998-01-01

    Isoamyl acetate is synthesized from isoamyl alcohol and acetyl coenzyme A by alcohol acetyltransferase (AATFase) in Saccharomyces cerevisiae and is hydrolyzed by esterases at the same time. We hypothesized that the balance of both enzyme activities was important for optimum production of isoamyl acetate in sake brewing. To test this hypothesis, we constructed yeast strains with different numbers of copies of the AATFase gene (ATF1) and the isoamyl acetate-hydrolyzing esterase gene (IAH1) and used these strains in small-scale sake brewing. Fermentation profiles as well as components of the resulting sake were largely alike; however, the amount of isoamyl acetate in the sake increased with an increasing ratio of AATFase/Iah1p esterase activity. Therefore, we conclude that the balance of these two enzyme activities is important for isoamyl acetate accumulation in sake mash. PMID:9758847

  6. Stable expression of mtlD gene imparts multiple stress tolerance in finger millet.

    PubMed

    Hema, Ramanna; Vemanna, Ramu S; Sreeramulu, Shivakumar; Reddy, Chandrasekhara P; Senthil-Kumar, Muthappa; Udayakumar, Makarla

    2014-01-01

    Finger millet is susceptible to abiotic stresses, especially drought and salinity stress, in the field during seed germination and early stages of seedling development. Therefore developing stress tolerant finger millet plants combating drought, salinity and associated oxidative stress in these two growth stages is important. Cellular protection through osmotic adjustment and efficient free radical scavenging ability during abiotic stress are important components of stress tolerance mechanisms in plants. Mannitol, an osmolyte, is known to scavenge hydroxyl radicals generated during various abiotic stresses and thereby minimize stress damage in several plant species. In this study transgenic finger millet plants expressing the mannitol biosynthetic pathway gene from bacteria, mannitol-1-phosphate dehydrogenase (mtlD), were developed through Agrobacterium tumefaciens-mediated genetic transformation. mtlD gene integration in the putative transgenic plants was confirmed by Southern blot. Further, performance of transgenic finger millet under drought, salinity and oxidative stress was studied at plant level in T1 generation and in T1 and T2 generation seedlings. Results from these experiments showed that transgenic finger millet had better growth under drought and salinity stress compared to wild-type. At plant level, transgenic plants showed better osmotic adjustment and chlorophyll retention under drought stress compared to the wild-type. However, the overall increase in stress tolerance of transgenics for the three stresses, especially for oxidative stress, was only marginal compared to other mtlD gene expressing plant species reported in the literature. Moreover, the Agrobacterium-mediated genetic transformation protocol developed for finger millet in this study can be used to introduce diverse traits of agronomic importance in finger millet.

  7. Yeast Cytosine Deaminase Mutants with Increased Thermostability Impart Sensitivity to 5-Fluorocytosine

    PubMed Central

    Stolworthy, Tiffany S.; Korkegian, Aaron M.; Willmon, Candice L.; Ardiani, Andressa; Cundiff, Jennifer; Stoddard, Barry L.; Black, Margaret E.

    2008-01-01

    SUMMARY Prodrug gene therapy (PGT) is a treatment strategy in which tumor cells are transfected with a 'suicide' gene that encodes a metabolic enzyme capable of converting a nontoxic prodrug into a potent cytotoxin. One of the most promising PGT enzymes is cytosine deaminase (CD), a microbial salvage enzyme that converts cytosine to uracil. CD also converts 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), an inhibitor of DNA synthesis and RNA function. Over 150 studies of cytosine deaminase-mediated PGT applications have been reported since 2000, all using wild-type enzymes. However, various forms of cytosine deaminase are limited by inefficient turnover of 5FC and/or limited thermostability. In a previous study we stabilized and extended the half-life of yeast cytosine deaminase (yCD) by repacking of its hydrophobic core at several positions distant from the active site. Here we report that random mutagenesis of residues selected based on alignment with similar enzymes, followed by selection for enhanced sensitization to 5FC, also produces an enzyme variant (yCD-D92E) with elevated Tm values and increased activity half-life. The new mutation is located at the enzyme's dimer interface, indicating that independent mutational pathways can lead to an increase in the temperature that induces protein unfolding and aggregation in thermal denaturation experiments measured by circular dichroism spectroscopy, and an increase in the half-life of enzyme activity at physiological temperature, as well as more subtle effect on enzyme kinetics. Each independently derived set of mutations significantly improves the enzyme's performance in PGT assays both in cell culture and in animal models. PMID:18291415

  8. Zinc supplementation imparts tolerance to arsenite stress in Hydrilla verticillata (L.f.) Royle.

    PubMed

    Srivastava, Sudhakar; Shrivastava, Manoj

    2017-04-03

    The present study was aimed to analyze the effects of external Zn supply on arsenic (As) toxicity in Hydrilla verticillata (L.f.) Royle. The plants were exposed to arsenite (AsIII; 10 μM) with or without 50 and 100 μM Zn. The level of As accumulation (μg g(-1) dw) after 2 and 4 days was not significantly affected by Zn supply. The plants showed a significant stimulation of the thiol metabolism (nonprotein thiols, cysteine, glutathione-S-transferase activity) upon As(III) exposure in the presence of Zn as compared to As(III) alone treatment. Besides, they did not experience significant toxicity, measured in terms of hydrogen peroxide and malondialdehyde accumulation, which are the indicators of oxidative stress. The minus Zn plants suffered from oxidative stress probably due to insufficient increase in thiols to counteract the stress. Stress amelioration by Zn supply was also evident from antioxidant enzyme activities, which came close to control levels with increasing Zn supply as compared to the increase observed in As(III) alone treatment. Variable Zn supply also modulated the level of photosynthetic pigments and restored them to control levels. In conclusion, an improved supply of Zn to plants was found to augment their ability to withstand As toxicity through enhanced thiol metabolism.

  9. Yeast cytosine deaminase mutants with increased thermostability impart sensitivity to 5-fluorocytosine.

    PubMed

    Stolworthy, Tiffany S; Korkegian, Aaron M; Willmon, Candice L; Ardiani, Andressa; Cundiff, Jennifer; Stoddard, Barry L; Black, Margaret E

    2008-03-28

    Prodrug gene therapy (PGT) is a treatment strategy in which tumor cells are transfected with a 'suicide' gene that encodes a metabolic enzyme capable of converting a nontoxic prodrug into a potent cytotoxin. One of the most promising PGT enzymes is cytosine deaminase (CD), a microbial salvage enzyme that converts cytosine to uracil. CD also converts 5-fluorocytosine (5FC) to 5-fluorouracil, an inhibitor of DNA synthesis and RNA function. Over 150 studies of CD-mediated PGT applications have been reported since 2000, all using wild-type enzymes. However, various forms of CD are limited by inefficient turnover of 5FC and/or limited thermostability. In a previous study, we stabilized and extended the half-life of yeast CD (yCD) by repacking of its hydrophobic core at several positions distant from the active site. Here we report that random mutagenesis of residues selected based on alignment with similar enzymes, followed by selection for enhanced sensitization to 5FC, also produces an enzyme variant (yCD-D92E) with elevated T(m) values and increased activity half-life. The new mutation is located at the enzyme's dimer interface, indicating that independent mutational pathways can lead to an increase in stability, as well as a more subtle effect on enzyme kinetics. Each independently derived set of mutations significantly improves the enzyme's performance in PGT assays both in cell culture and in animal models.

  10. Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.

    PubMed

    Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D

    2011-01-01

    Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

  11. Imparting super hydro/oleophobic properties to cotton fabric by means of molecular and nanoparticles vapor deposition methods

    NASA Astrophysics Data System (ADS)

    Aminayi, Payam; Abidi, Noureddine

    2013-12-01

    Super hydro/oleophobic cotton fabrics were prepared using nanoparticle vapor deposition and molecular vapor deposition techniques. The surface was roughened by trimethylaluminum/water nanoparticles followed by functionalization with (tridecafluoro-1,1,2,2-tetrahydrooctyl)trichlorosilane. This process imparted unique hydro/oleophobic properties (contact angle >160°). In contrast to wet chemistry processes, the chemicals used and the thickness of the coatings produced by this method could be controlled precisely, which allowed for the minimization of waste generation while preserving the original properties of the fabric. Dynamic contact angles were measured and the fabrics that were coated using this technique showed low-contact-angle hysteresis properties. Scanning electron microscopy and universal attenuated total reflectance Fourier transform infrared spectroscopy confirmed the formation of a nanostructure-roughened surface. Drop dynamics such as the force of droplet movement, work of adhesion, and surface free energy were also calculated.

  12. [Clinical and diagnostic importance of the evaluation of the Ig proteases activity in children with intestinal dysbacteriosis].

    PubMed

    Zinkevich, O D; Bondarenko, V M; Tiurin, Iu A; Safina, N A; Anokhin, V A

    2004-01-01

    The specific activity of serine, metal dependent and thiolic Ig proteases in the coprofiltrates of children with manifestations of intestinal dysbacteriosis was determined by the enzyme immunoassay. 56 children with pronounced symptoms of intestinal disorders (37 children aged up to 1 year and 19 children over 1 year) were examined. A group of 25 clinically healthy children was used as control. Simultaneously with protease activity of coprofiltrates, there was detected the level of Ig-degrading activity of the opportunistic bacteria islolates of different taxonomic groups from feces of children with dysbacteriosis of different severity (as determined by the classical bacteriological method). The evaluation of the Ig-proteolytic activity of fecal supernatants, associated with the presence of serine, metal-dependent and thiolic proteases in the intestine, as well as detection of such proteases in microbial isolates, seems to be highly important for the diagnosis of intestinal disorders in children and is recommended for screening of intestinal dysbacteriosis.

  13. Determining the Minimally Important Difference in the Clinical Disease Activity Index For Improvement and Worsening in Early Rheumatoid Arthritis

    PubMed Central

    Curtis, JR; Yang, S; Chen, L; Pope, JE; Keystone, EC; Haraoui, B; Boire, G; Thorne, JC; Tin, D; Hitchon, CA; Bingham, CO; Bykerk, VP

    2015-01-01

    Background Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimally clinically important differences (MCID) for some measures, such as the clinical disease activity index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. Methods Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cutpoints were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Specificity, positive predictive value and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, HAQ and DAS28 improvement. Discrimination was examined using area under receiver operator curves (ROC). Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. Results A total of 578 patients (mean (SD) age 54.1 (15.3) years; 75% women, median (IQR) disease duration 5.3 (3.3, 8.0) months) contributed 1169 visit pairs to the improvement analysis. The MCID cutpoints for improvement were 12 (patients starting in high disease activity, CDAI>22), 6 (moderate, CDAI 10–22), and 1 (low disease activity, CDAI <10). Performance characteristics were acceptable using these cutpoints for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. Conclusions These minimally important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice. PMID:25988705

  14. Dissipation of the energy imparted by mid-latitude storms in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Jouanno, Julien; Capet, Xavier; Madec, Gurvan; Roullet, Guillaume; Klein, Patrice

    2016-06-01

    The aim of this study is to clarify the role of the Southern Ocean storms on interior mixing and meridional overturning circulation. A periodic and idealized numerical model has been designed to represent the key physical processes of a zonal portion of the Southern Ocean located between 70 and 40° S. It incorporates physical ingredients deemed essential for Southern Ocean functioning: rough topography, seasonally varying air-sea fluxes, and high-latitude storms with analytical form. The forcing strategy ensures that the time mean wind stress is the same between the different simulations, so the effect of the storms on the mean wind stress and resulting impacts on the Southern Ocean dynamics are not considered in this study. Level and distribution of mixing attributable to high-frequency winds are quantified and compared to those generated by eddy-topography interactions and dissipation of the balanced flow. Results suggest that (1) the synoptic atmospheric variability alone can generate the levels of mid-depth dissipation frequently observed in the Southern Ocean (10-10-10-9 W kg-1) and (2) the storms strengthen the overturning, primarily through enhanced mixing in the upper 300 m, whereas deeper mixing has a minor effect. The sensitivity of the results to horizontal resolution (20, 5, 2 and 1 km), vertical resolution and numerical choices is evaluated. Challenging issues concerning how numerical models are able to represent interior mixing forced by high-frequency winds are exposed and discussed, particularly in the context of the overturning circulation. Overall, submesoscale-permitting ocean modeling exhibits important delicacies owing to a lack of convergence of key components of its energetics even when reaching Δx = 1 km.

  15. Features of Modularly Assembled Compounds That Impart Bioactivity Against an RNA Target

    PubMed Central

    Rzuczek, Suzanne G.; Gao, Yu; Tang, Zhen-Zhi; Thornton, Charles A.; Kodadek, Thomas; Disney, Matthew D.

    2013-01-01

    Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of a general program to study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the non-coding expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)exp. Herein, we present a rigorous study to elucidate features in modularly assembled compounds that afford bioactivity. Different modular assembly scaffolds were investigated including polyamines, α-peptides, β-peptides, and peptide tertiary amides (PTAs). Based on activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely PTAs, are optimal. Notably, we determined that r(CUG)exp is the target of the optimal PTA in cellular models and that the optimal PTA improves DM1-associated defects in a mouse model. Biophysical analyses were employed to investigate potential sources of bioactivity. These investigations show that modularly assembled compounds have increased residence times on their targets and faster on rates than the RNA-binding modules from which they were derived and faster on rates than the protein that binds r(CUG)exp, the inactivation of which gives rise to DM1-associated defects. These studies provide information about features of small molecules that are programmable for targeting RNA, allowing for the facile optimization of therapeutics or chemical probes against other cellular RNA targets. PMID:24032410

  16. Imparting commercial antimicrobial dressings with low-adherence to burn wounds.

    PubMed

    Asghari, Sogol; Logsetty, Sarvesh; Liu, Song

    2016-06-01

    The objective of our study was to decrease the wound adherence of commercial silver based wound dressings by depositing a non-adherent layer. Our hypothesis was that this non-adherent layer will lower the dressing's adherence to burn wounds without compromising the antimicrobial activity or increasing the cytotoxicity. A polyacrylamide (PAM) hydrogel layer was grafted on two commercial silver antimicrobial dressings (silver nanocrystal dressing (NC) and silver plated dressing (SP)) using a proprietary technique. The grafted PAM served as the non-adherent layer. Dressing adherence was measured with a previously published in vitro gelatin model using an Instron mechanical force testing instrument. The dressings were challenged with two clinically retrieved bacterial strains (Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant (MDR) Pseudomonas aeruginosa) with both a disk diffusion test, and a suspension antibacterial test. The cytotoxicity of samples to human neonatal fibroblast cells was evaluated with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Both untreated dressings showed high peeling energy: 2070±453J/m(2) (NC) and 669±68J/m(2) (SP), that decreased to 158±119J/m(2) (NC) and 155±138J/m(2) (SP) with the PAM deposition. Addition of the PAM caused no significant difference in zone of inhibition (ZOI) (disk diffusion test) or antibacterial kinetics (suspension test) against both bacteria (p>0.05, n=6) in either dressing. Survival of fibroblasts was improved by the PAM grafting from 48±5% to 60±3% viable cells in the case of NC and from 55±8% to 61±4% viable cells in SP (p<0.05, n=12). It was concluded that PAM as a non-adherent layer significantly decreases the adherence of these two commercial antimicrobial dressings in an in vitro gelatin model while preserving their antimicrobial efficacy, and reducing their cytotoxicity.

  17. Features of modularly assembled compounds that impart bioactivity against an RNA target.

    PubMed

    Rzuczek, Suzanne G; Gao, Yu; Tang, Zhen-Zhi; Thornton, Charles A; Kodadek, Thomas; Disney, Matthew D

    2013-10-18

    Transcriptomes provide a myriad of potential RNAs that could be the targets of therapeutics or chemical genetic probes of function. Cell-permeable small molecules, however, generally do not exploit these targets, owing to the difficulty in the design of high affinity, specific small molecules targeting RNA. As part of a general program to study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)(exp). Herein, we present a rigorous study to elucidate features in modularly assembled compounds that afford bioactivity. Different modular assembly scaffolds were investigated, including polyamines, α-peptides, β-peptides, and peptide tertiary amides (PTAs). On the basis of activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely, PTAs, are optimal. Notably, we determined that r(CUG)(exp) is the target of the optimal PTA in cellular models and that the optimal PTA improves DM1-associated defects in a mouse model. Biophysical analyses were employed to investigate potential sources of bioactivity. These investigations show that modularly assembled compounds have increased residence times on their targets and faster on rates than the RNA-binding modules from which they were derived. Moreover, they have faster on rates than the protein that binds r(CUG)(exp), the inactivation of which gives rise to DM1-associated defects. These studies provide information about features of small molecules that are programmable for targeting RNA, allowing for the facile optimization of therapeutics or chemical probes against other cellular RNA targets.

  18. {beta}-Catenin stabilization imparts crypt progenitor phenotype to hyperproliferating colonic epithelia

    SciTech Connect

    Sellin, Joseph H.; Wang Yu; Singh, Pomila; Umar, Shahid

    2009-01-01

    Utilizing the Citrobacter rodentium (CR)-induced transmissible murine colonic hyperplasia (TMCH) model, we provide mechanistic basis of changes in {beta}-catenin/APC/CKI{epsilon} leading to progression and/or regression of hyperplasia in vivo. In response to CR-induced TMCH, crypt lengths increased significantly between days 6-27 post-infection, followed by a steep decline by day 34. {beta}-Cat{sup 45}/total {beta}-catenin were elevated on day 1 post-infection, preceding changes in crypt length, and persisted for 27 days before declining by day 34. Importantly, cellular CKI{epsilon} and {beta}-catenin co-immunoprecipitated and exhibited remarkable parallel changes in kinetics during hyperplasia/regression phases. {beta}-catenin, phosphorylated at Ser33,37 and Thr41 ({beta}-cat{sup 33,37/41}), was low till day 12, followed by gradual increase until day 27 before declining by day 34. GSK-3{beta} exhibited significant Ser{sup 9}-phosphorylation/inactivation at days 6-12 with partial recovery at days 27-34. Wild type (wt) APC (p312) levels increased at day 6 with transient proteolysis/truncation to p130 form between days 12 and 15; p312 reappeared by day 19 and returned to baseline by day 34. The kinetics of {beta}-Cat{sup 45}/{beta}-catenin nuclear accumulation and acetylation (Ac-{beta}-Cat{sup Lys49}) from days 6 to 27, followed by loss of phosphorylation/acetylation by day 34 was almost identical; Tcf-4 co-immunoprecipitated with {beta}-Cat{sup 45}/{beta}-catenin and localized immunohistochemically to {beta}-Cat{sup 41/45}-positive regions leading to elevated cyclin D1 expression, during the hyperproliferative, but not regression phases of TMCH. CKI{epsilon} mediated phosphorylation of {beta}-Cat{sup 45}, resulting in stabilization/nuclear translocation of {beta}-Cat{sup 45} may be critical for maintaining proliferation at days 6-27. Reversal of GSK-3{beta} phosphorylation and APC changes may be equally critical during the regression phase from days 27 to 34.

  19. The importance of delineating networks by activity type in bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida

    PubMed Central

    Gazda, Stefanie; Iyer, Swami; Killingback, Timothy; Connor, Richard; Brault, Solange

    2015-01-01

    Network analysis has proved to be a valuable tool for studying the behavioural patterns of complex social animals. Often such studies either do not distinguish between different behavioural states of the organisms or simply focus attention on a single behavioural state to the exclusion of all others. In either of these approaches it is impossible to ascertain how the behavioural patterns of individuals depend on the type of activity they are engaged in. Here we report on a network-based analysis of the behavioural associations in a population of bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida. We consider three distinct behavioural states—socializing, travelling and foraging—and analyse the association networks corresponding to each activity. Moreover, in constructing the different activity networks we do not simply record a spatial association between two individuals as being either present or absent, but rather quantify the degree of any association, thus allowing us to construct weighted networks describing each activity. The results of these weighted activity networks indicate that networks can reveal detailed patterns of bottlenose dolphins at the population level; dolphins socialize in large groups with preferential associations; travel in small groups with preferential associates; and spread out to forage in very small, weakly connected groups. There is some overlap in the socialize and travel networks but little overlap between the forage and other networks. This indicates that the social bonds maintained in other activities are less important as they forage on dispersed, solitary prey. The overall network, not sorted by activity, does not accurately represent any of these patterns. PMID:26064611

  20. Increased aerobic glycolysis is important for the motility of activated VSMC and inhibited by indirubin-3′-monoxime

    PubMed Central

    Heiss, Elke H.; Schachner, Daniel; Donati, Maddalena; Grojer, Christoph S.; Dirsch, Verena M.

    2016-01-01

    Increased aerobic glycolysis is a recognized feature of multiple cellular phenotypes and offers a potential point for drug interference, as pursued by anti-tumor agents targeting the Warburg effect. This study aimed at examining the role of aerobic glycolysis for migration of vascular smooth muscle cells (VSMC) and its susceptibility to the small molecule indirubin-3′-monoxime (I3MO). Activation of VSMC with platelet-derived growth factor (PDGF) resulted in migration and increased glycolytic activity which was accompanied by an increased glucose uptake and hexokinase (HK) 2 expression. Inhibition of glycolysis or hexokinase by pharmacological agents or siRNA-mediated knockdown significantly reduced the migratory behavior in VSMC without affecting cell viability or early actin cytoskeleton rearrangement. I3MO, previously recognized as inhibitor of VSMC migration, was able to counteract the PDGF-activated increase in glycolysis and HK2 abundance. Activation of signal transducer and activator of transcription (STAT) 3 could be identified as crucial event in upregulation of HK2 and glycolytic activity in PDGF-stimulated VSMC and as point of interference for I3MO. I3MO did not inhibit hypoxia-inducible factor (HIF)1α-dependent transcription nor influence miRNA 143 levels, other potential regulators of HK2 levels. Overall, we demonstrate that increased aerobic glycolysis is an important factor for the motility of activated VSMC and that the anti-migratory property of I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 signaling axis. PMID:27185663

  1. Pupicidal and repellent activities of Pogostemon cablin essential oil chemical compounds against medically important human vector mosquitoes

    PubMed Central

    Gokulakrishnan, J; Kuppusamy, Elumalai; Shanmugam, Dhanasekaran; Appavu, Anandan; Kaliyamoorthi, Krishnappa

    2013-01-01

    Objective To determine the repellent and pupicidal activities of Pogostemon cablin (P. cablin) chemical compositions were assayed for their toxicity against selected important vector mosquitoes, viz., Aedes aegypti (Ae. aegypti), Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus) (Diptera: Culicidae). Methods The plants dry aerial parts were subjected to hydrodistillation using a modified Clevenger-type apparatus. The composition of the essential oil was analyzed by Gas Chromatography (GC) and GC mass spectrophotometry. Evaluation was carried out in a net cage (45 cm×30 cm×45 cm) containing 100 blood starved female mosquitoes and were assayed in the laboratory condition by using the protocol of WHO 2010. The repellent activity of P. cablin chemical compositions at concentration of 2mg/cm2were applied on skin of fore arm in man and exposed against adult female mosquitoes. The pupicidal activity was determined against selected important vector mosquitoes to concentration of 100 mg/L and mortality of each pupa was recorded after 24 h of exposure to the compounds. Results Chemical constituents of 15 compounds were identified in the oil of P.cablin compounds representing to 98.96%. The major components in essential oil were â-patchoulene, á-guaiene, ã-patchoulene, á-bulnesene and patchouli alcohol. The repellent activity of patchouli alcohol compound was found to be most effective for repellent activity and 2 mg/cm2 concentration provided 100% protection up to 280 min against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, respectively. Similarly, pupae exposed to 100 mg/L concentrations of P. cablin chemical compositions. Among five compounds tested patchouli alcoholwas found to be most effective for pupicidal activity provided 28.44, 26.28 and 25.36 against Ae.aegypti, An.stephensi and Cx. quinquefasciatus, respectively. The percent adult emergence was inversely proportional to the concentration of compounds and directly

  2. Mitochondrial and Oxidative Stress-Mediated Activation of Protein Kinase D1 and Its Importance in Pancreatic Cancer

    PubMed Central

    Döppler, Heike; Storz, Peter

    2017-01-01

    Due to alterations in their metabolic activity and decreased mitochondrial efficiency, cancer cells often show increased generation of reactive oxygen species (ROS), but at the same time, to avoid cytotoxic signaling and to facilitate tumorigenic signaling, have mechanism in place that keep ROS in check. This requires signaling molecules that convey increases in oxidative stress to signal to the nucleus to upregulate antioxidant genes. Protein kinase D1 (PKD1), the serine/threonine kinase, is one of these ROS sensors. In this mini-review, we highlight the mechanisms of how PKD1 is activated in response to oxidative stress, so far known downstream effectors, as well as the importance of PKD1-initiated signaling for development and progression of pancreatic cancer. PMID:28361035

  3. Importance of AOX pathway in optimizing photosynthesis under high light stress: role of pyruvate and malate in activating AOX.

    PubMed

    Dinakar, Challabathula; Raghavendra, Agepati S; Padmasree, Kollipara

    2010-05-01

    The present study shows the importance of alternative oxidase (AOX) pathway in optimizing photosynthesis under high light (HL). The responses of photosynthesis and respiration were monitored as O(2) evolution and O(2) uptake in mesophyll protoplasts of pea pre-incubated under different light intensities. Under HL (3000 micromol m(-2) s(-1)), mesophyll protoplasts showed remarkable decrease in the rates of NaHCO(3)-dependent O(2) evolution (indicator of photosynthetic carbon assimilation), while decrease in the rates of respiratory O(2) uptake were marginal. While the capacity of AOX pathway increased significantly by two fold under HL, the capacity of cytochrome oxidase (COX) pathway decreased by >50% compared with capacities under darkness and normal light (NL). Further, the total cellular levels of pyruvate and malate, which are assimilatory products of active photosynthesis and stimulators of AOX activity, were increased remarkably parallel to the increase in AOX protein under HL. Upon restriction of AOX pathway using salicylhydroxamic acid (SHAM), the observed decrease in NaHCO(3)-dependent O(2) evolution or p-benzoquinone (BQ)-dependent O(2) evolution [indicator of photosystem II (PSII) activity] and the increase in total cellular levels of pyruvate and malate were further aggravated/promoted under HL. The significance of raised malate and pyruvate levels in activation of AOX protein/AOX pathway, which in turn play an important role in dissipating excess chloroplastic reducing equivalents and sustenance of photosynthetic carbon assimilation to balance the effects of HL stress on photosynthesis, was depicted as a model.

  4. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells.

    PubMed

    Wang, Ronghua; Sun, Qian; Wang, Peng; Liu, Man; Xiong, Si; Luo, Jing; Huang, Hai; Du, Qiang; Geller, David A; Cheng, Bin

    2016-02-02

    Human hepatocellular carcinoma (HCC) is driven and maintained by liver cancer stem cells (LCSCs) that display stem cell properties. These LCSCs are promoted by the intersecting of Notch and Wnt/β-Catenin signaling pathways. In this study, we demonstrate that LCSCs with markers CD90, CD24, CD13, and CD133 possess stem properties of self-renewal and tumorigenicity in NOD/SCID mice. The increased expression of these markers was correlated with advanced disease stage, larger tumors, and worse overall survival in 61 HCC cases. We also found that both Notch and Wnt/β-catenin signaling pathways played important roles in increasing the stem-ness characteristics of LCSCs. Our data suggested that Notch1 was downstream of Wnt/β-catenin. The active form of Notch1 intracellular domain (NICD) expression depended on Wnt/β-catenin pathway activation. Moreover, Notch1 negatively contributed to Wnt/β-catenin signaling modulation. Knock down of Notch1 with lentivirus N1ShRNA up-regulated the active form of β-catenin. Ectopic expression of NICD with LV-Notch1 in LCSCs attenuated β-catenin/TCF dependent luciferase activity significantly. In addition, there was a non-proteasome mediated feedback loop between Notch1 and Wnt/β-catenin signaling in LCSCs. The central role of Notch and the Wnt/β-catenin signaling pathway in LCSCs may provide an attractive therapeutic strategy against HCC.

  5. Effects of periplocoside X on midgut cells and digestive enzymes activity of the soldiers of red imported fire ant.

    PubMed

    Li, Yan; Zeng, Xin-Nian

    2013-07-01

    The pathological effects of ingested periplocoside X, an insecticidal component isolated from the root of Periploca sepium Bunge, on the midgut epithelial cells of the soldiers of red imported fire ant were studied and the symptom was described. The results showed that periplocoside X could induce a severe, time-dependent cytotoxicity in the midgut epithelial cells. An optical microscopy showed that epithelial cells swelled firstly and then lysed. Transmission electron microscopy (TEM) showed that numerous swollen lysosomes were appeared, microvilli were disrupted and sloughed off, and the numbers of the rough endoplasmic reticulum and the mitochondria decreased sharply in earlier stage. Numerous vacuoles were observed in the later stage. Finally, periplocoside X resulted in cell death by cytolysis. Assay of main three digestive enzymes activity indicated that amylase activity was significantly inhibited, but no significant changes were seen for lipase activity and total protease activity. So it is suggested that periplocoside X induced mainly to organic damage of midgut epithelium cells of insect. In all, insect midgut is one of targets for periplocoside X.

  6. Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection.

    PubMed

    Steigedal, Magnus; Marstad, Anne; Haug, Markus; Damås, Jan K; Strong, Roland K; Roberts, Pacita L; Himpsl, Stephanie D; Stapleton, Ann; Hooton, Thomas M; Mobley, Harry L T; Hawn, Thomas R; Flo, Trude H

    2014-12-15

    Competition for iron is a critical component of successful bacterial infections, but the underlying in vivo mechanisms are poorly understood. We have previously demonstrated that lipocalin 2 (LCN2) is an innate immunity protein that binds to bacterial siderophores and starves them for iron, thus representing a novel host defense mechanism to infection. In the present study we show that LCN2 is secreted by the urinary tract mucosa and protects against urinary tract infection (UTI). We found that LCN2 was expressed in the bladder, ureters, and kidneys of mice subject to UTI. LCN2 was protective with higher bacterial numbers retrieved from bladders of Lcn2-deficient mice than from wild-type mice infected with the LCN2-sensitive Escherichia coli strain H9049. Uropathogenic E. coli mutants in siderophore receptors for salmochelin, aerobactin, or yersiniabactin displayed reduced fitness in wild-type mice, but not in mice deficient of LCN2, demonstrating that LCN2 imparts a selective pressure on bacterial growth in the bladder. In a human cohort of women with recurrent E. coli UTIs, urine LCN2 levels were associated with UTI episodes and with levels of bacteriuria. The number of siderophore systems was associated with increasing bacteriuria during cystitis. Our data demonstrate that LCN2 is secreted by the urinary tract mucosa in response to uropathogenic E. coli challenge and acts in innate immune defenses as a colonization barrier that pathogens must overcome to establish infection.

  7. Synergistic Behavior of Tubes, Junctions, and Sheets Imparts Mechano-Mutable Functionality in 3D Porous Boron Nitride Nanostructures.

    PubMed

    Sakhavand, Navid; Shahsavari, Rouzbeh

    2014-10-02

    One-dimensional (1D) boron nitride nanotube (BNNT) and 2D hexagonal BN (h-BN) are attractive for demonstrating fundamental physics and promising applications in nano-/microscale devices. However, there is a high anisotropy associated with these BN allotropes as their excellent properties are either along the tube axis or in-plane directions, posing an obstacle in their widespread use in technological and industrial applications. Herein, we report a series of 3D BN prototypes, namely, pillared boron nitride (PBN), by fusing single-wall BNNT and monolayer h-BN aimed at filling this gap. We use density functional theory and molecular dynamics simulations to probe the diverse mechano-mutable properties of PBN prototypes. Our results demonstrate that the synergistic effect of the tubes, junctions, and sheets imparts cooperative deformation mechanisms, which overcome the intrinsic limitations of the PBN constituents and provide a number of superior characteristics including 3D balance of strength and toughness, emergence of negative Poisson's ratio, and elimination of strain softening along the armchair orientation. These features, combined with the ultrahigh surface area and lightweight structure, render PBN as a 3D multifunctional template for applications in graphene-based nanoelectronics, optoelectronics, gas storage, and functional composites with fascinating in-plane and out-of-plane tailorable properties.

  8. Synergistic Behavior of Tubes, Junctions, and Sheets Imparts Mechano-Mutable Functionality in 3D Porous Boron Nitride Nanostructures

    PubMed Central

    2015-01-01

    One-dimensional (1D) boron nitride nanotube (BNNT) and 2D hexagonal BN (h-BN) are attractive for demonstrating fundamental physics and promising applications in nano-/microscale devices. However, there is a high anisotropy associated with these BN allotropes as their excellent properties are either along the tube axis or in-plane directions, posing an obstacle in their widespread use in technological and industrial applications. Herein, we report a series of 3D BN prototypes, namely, pillared boron nitride (PBN), by fusing single-wall BNNT and monolayer h-BN aimed at filling this gap. We use density functional theory and molecular dynamics simulations to probe the diverse mechano-mutable properties of PBN prototypes. Our results demonstrate that the synergistic effect of the tubes, junctions, and sheets imparts cooperative deformation mechanisms, which overcome the intrinsic limitations of the PBN constituents and provide a number of superior characteristics including 3D balance of strength and toughness, emergence of negative Poisson’s ratio, and elimination of strain softening along the armchair orientation. These features, combined with the ultrahigh surface area and lightweight structure, render PBN as a 3D multifunctional template for applications in graphene-based nanoelectronics, optoelectronics, gas storage, and functional composites with fascinating in-plane and out-of-plane tailorable properties. PMID:25289114

  9. Tip-to-tip interaction in the crystal packing of PACSIN 2 is important in regulating tubulation activity.

    PubMed

    Bai, Xiaoyun; Zheng, Xiaofeng

    2013-09-01

    The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various membrane deformations, such as actin reorganization, vesicle transport and microtubule movement. Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops, and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity. Here, from the crystal packing of PACSIN 2, we observed a tight tip-to-tip interaction, in addition to the wedge loop-mediated lateral interaction. With this tip-to-tip interaction, the whole packing of PACSIN 2 shows a spiral-like assembly with a central hole from the top view. Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2, indicating that tip-to-tip interaction plays an important role in membrane deformation activity. Together with our previous study, we proposed a packing model for the assembly of PACSIN 2 on membrane, where the proteins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to generate various diameter tubules.

  10. Importance of the tuning of band position in optimizing the electronic coupling and photocatalytic activity of nanocomposite

    SciTech Connect

    Jin, Xiaoyan; Mok, Eun Kyung; Baek, Ji-Won; Park, Sang-Hyun; Hwang, Seong-Ju

    2015-10-15

    The electronic coupling and photocatalytic activity of Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite can be optimized by the fine-tuning of the band position of titanium oxide with nitrogen doping. The increase of the valence band energy of TiO{sub 2} by N-doping leads not only to the enhanced absorption of visible light but also to the promoted hole transfer from Ag{sub 2}CO{sub 3} to TiO{sub 2}, resulting in the efficient spatial separation of photogenerated electrons and holes. While the undoped Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite shows an inferior photocatalytic activity to the pure Ag{sub 2}CO{sub 3}, the photocatalyst performance of N-doped nanocomposite is better than those of Ag{sub 2}CO{sub 3} and undoped Ag{sub 2}CO{sub 3}–TiO{sub 2} nanocomposite. This observation underscores a significant enhancement of the photocatalytic activity of nanocomposite upon N-doping, a result of enhanced electronic coupling between the hybridized species. The present results clearly demonstrate the importance of the fine-tuning of band position in optimizing the photocatalytic activity of hybrid-type photocatalysts. - Highlights: • The band position of Ag{sub 2}CO{sub 3}–TiO{sub 2} can be effectively tailored by nitrogen doping. • The N-doping leads to the improvement of charge separation. • The N-doped Ag{sub 2}CO{sub 3}–TiO{sub 2} shows high photocatalytic activity.

  11. Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: The N-terminal region is more important than enzymatic activity

    PubMed Central

    Rouault, Morgane; Rash, Lachlan D.; Escoubas, Pierre; Boilard, Eric; Bollinger, James; Lomonte, Bruno; Maurin, Thomas; Guillaume, Carole; Canaan, Stéphane; Deregnaucourt, Christiane; Schrével, Joseph; Doglio, Alain; Gutiérrez, José María; Lazdunski, Michel; Gelb, Michael H.; Lambeau, Gérard

    2009-01-01

    Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, an homologous but non toxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1–22) of OS2, but not the central one (residues 58–89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102–119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity. PMID:16669624

  12. Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: the N-terminal region is more important than enzymatic activity.

    PubMed

    Rouault, Morgane; Rash, Lachlan D; Escoubas, Pierre; Boilard, Eric; Bollinger, James; Lomonte, Bruno; Maurin, Thomas; Guillaume, Carole; Canaan, Stéphane; Deregnaucourt, Christiane; Schrével, Joseph; Doglio, Alain; Gutiérrez, José María; Lazdunski, Michel; Gelb, Michael H; Lambeau, Gérard

    2006-05-09

    Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, a homologous but nontoxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1-22) of OS2, but not the central one (residues 58-89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102-119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera, which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity.

  13. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation

    PubMed Central

    Zelle, Dorien M.; Corpeleijn, Eva; Klaassen, Gerald; Schutte, Elise; Navis, Gerjan; Bakker, Stephan J. L.

    2016-01-01

    Background Physical activity (PA) and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR) meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self-efficacy as barriers to PA in RTR. Methods RTR were investigated between 2001–2003. The Tampa Score of Kinesiophobia–Dutch Version (TSK-11) was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). Results A total of 487 RTR (age 51±12 years, 55% men) were studied. Median score [interquartile range] on TSK-11 was 22 [17–26]. Low physical self-efficacy (Exp B:0.41[0.31–0.54], p<0.001) and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03–1.63],p = 0.03) were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73%) of the effect of fear of movement on PA was explained by low physical self-efficacy. Conclusions This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation. PMID:26844883

  14. Importance of surface diffusivities in pesticide adsorption kinetics onto granular versus powdered activated carbon: experimental determination and modeling.

    PubMed

    Baup, S; Wolbert, D; Laplanche, A

    2002-10-01

    Three pesticides (atrazine, bromoxynil and diuron) and two granular activated carbons are involved in equilibrium and kinetic adsorption experiments. Equilibrium is represented by Freundlich isotherm law and kinetic is described by the Homogeneous Surface Diffusion Model, based on external mass transfer and intraparticle surface diffusion. Equilibrium and long-term experiments are conducted to compare Powdered Activated Carbon and Granular Activated Carbon. These first investigations show that crushing GAC into PAC improves the accessibility of the adsorption sites without increasing the number of these sites. In a second part, kinetics experiments are carried out using a Differential Column Batch Reactor. Thanks to this experimental device, the external mass transfer coefficient k(f) is calculated from empirical correlation and the effect of external mass transfer on adsorption is likely to be minimized. In order to obtain the intraparticle surface diffusion coefficient D. for these pesticides, comparisons between experimental kinetic data and simulations are conducted and the best agreement leads to the Ds coefficient. This procedure appears to be an efficient way to acquire surface diffusion coefficients for the adsorption of pesticides onto GAC. Finally it points out the role of surface diffusivity in the adsorption rate. As a matter of fact, even if the amount of the target-compound that could be potentially adsorbed is really important, its surface diffusion coefficient may be small, so that its adsorption may not have enough contact time to be totally achieved.

  15. Erythroid Krüppel-like factor (EKLF) contains a multifunctional transcriptional activation domain important for inter- and intramolecular interactions.

    PubMed Central

    Chen, X; Bieker, J J

    1996-01-01

    Erythroid Krüppel-like factor (EKLF) is a red cell-restricted transcriptional activator that plays a dominant role in establishing high levels of beta-globin gene expression during erythroid ontogeny. Although its DNA binding domain belongs to the well-studied class of Krüppel-like zinc fingers, its proline-rich activation region has not been thoroughly examined. We have analyzed this region by monitoring the functional effects of its mutagenesis upon EKLF activity in vivo and in vitro. First, using co-transfection assays, we find that the transactivation region contains discrete stimulatory and inhibitory subdomains. Second, in vitro binding assays indicate that the inhibitory domain exerts its effect in cis by interfering with DNA binding. Third, in vivo competition assays demonstrate that EKLF interacts with a positive-acting cellular factor, and that the domain responsible for this trans interaction lies within a 40 amino acid sequence that is coincident with the EKLF minimal transactivation domain. Finally, site-directed mutagenesis of this domain implies that conformation and/or phosphorylation status of its central core may be critical for such interactions. These results point towards post-translational steric and/or allosteric control of EKLF function that may be important not just for its DNA binding ability, but also for its potential to interact with other proteins that fully establish the correct stereospecific array leading to efficient switching of beta-globin transcription during development. Images PMID:8918466

  16. Importance of nuclear localization for the apoptosis-induced activity of a fungal galectin AAL (Agrocybe aegerita lectin)

    SciTech Connect

    Liang, Yi; Feng, Lei; Tong, Xin; Wang, Kun; Li, De Feng; Lin, Jia Cheng; Tang, Zi Jian; Liu, Hong Hong; Jiang, Shuai; Guo, Lin; Wang, Da Cheng; Sun, Hui

    2009-08-28

    Agrocybe aegerita lectin (AAL) was identified previously in our group as a novel galectin from medicinal fungi Agrocybe aegerita, and has been shown to effectively induce cancer cell cycle arrest and apoptosis in vitro and tumor regression in vivo. Here, AAL was observed to translocate into the HeLa cell nucleus and induce cell apoptosis when it was predominantly in the nucleus. The N-terminus and C-terminus of AAL were required for nuclear localization. Site mutated proteins were generated based on AAL structure. Dimer interface mutant I25G, carbohydrate recognition domain (CRD) mutant R63H, and loop region mutant L33A could not enter the nucleus and lost the ability to induce apoptosis. CRD mutant H59Q and loop region mutant I144G maintained nuclear localization activity, and H59Q retained residual bioability but I144G had no activity, indicating that nuclear localization is important but not sufficient for AAL to become apoptotically active. Our findings provide a novel antitumor mechanism of fungal galectin.

  17. Toward understanding allosteric activation of thrombin: a conjecture for important roles of unbound Na(+) molecules around thrombin.

    PubMed

    Kurisaki, Ikuo; Takayanagi, Masayoshi; Nagaoka, Masataka

    2015-03-05

    We shed light on important roles of unbound Na(+) molecules in enzymatic activation of thrombin. Molecular mechanism of Na(+)-activation of thrombin has been discussed in the context of allostery. However, the recent challenge to redesign K(+)-activated thrombin revealed that the allosteric interaction is insufficient to explain the mechanism. Under these circumstances, we have examined the roles of unbound Na(+) molecule in maximization of thrombin-substrate association reaction rate. We performed all-atomic molecular dynamics (MD) simulations of thrombin in the presence of three different cations; Li(+), Na(+), and Cs(+). Although these cations are commonly observed in the vicinity of the S1-pocket of thrombin, smaller cations are distributed more densely and extensively than larger ones. This suggests the two observation rules: (i) thrombin surrounded by Na(+) is at an advantage in the initial step of association reaction, namely, the formation of an encounter complex ensemble, and (ii) the presence of Na(+) molecules does not necessarily have an advantage in the final step of association reaction, namely, the formation of the stereospecific complex. In conclusion, we propose a conjecture that unbound Na(+) molecules also affect the maximization of rate constant of thrombin-substrate association reaction through optimally forming an encounter complex ensemble.

  18. Synthesis and biological activities of some pseudo-peptide analogues of tetragastrin: the importance of the peptide backbone.

    PubMed

    Martinez, J; Bali, J P; Rodriguez, M; Castro, B; Magous, R; Laur, J; Lignon, M F

    1985-12-01

    Pseudo-peptide analogues of the C-terminal tetrapeptide of gastrin, in which a peptide bond has been replaced by a CH2-NH bond, i.e. (tert-butyloxycarbonyl)-L-tryptophyl-psi (CH2-NH)-L-leucyl-L-aspartyl-L-phenylalanine amide (8), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-psi (CH2-NH)-L-aspartyl-L-phenylalanine amide (13), (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-psi (CH2NH)-L-phenylalanine amide (20), were synthesized. The pseudo-peptides 8 and 13 were shown to have the same affinity as (tert-butyloxycarbonyl)-L-tryptophyl-L-leucyl-L-aspartyl-L-phenylalanine amide (21) for the gastrin receptor on isolated mucosal cells. The pseudo-peptide 20 exhibited lower affinity (IC50 congruent to 10(-5) M). The biological activity of these pseudo-peptides was studied on acid secretion in the anesthetized rat. Compound 8 stimulated acid secretion, identically with that of 21. Compound 13 did not exhibit any agonist activity but was able to antagonize the action of gastrin (ED50 = 0.3 mg/kg). Compound 20 did not show any agonist activity but was able to inhibit gastrin-induced acid secretion, with lower potency (ED50 = 15 mg/kg). The importance of the peptide bonds in the mode of action of gastrin is discussed, and a hypothetical approach of the mechanism of action is presented.

  19. Gingerols and shogaols: Important nutraceutical principles from ginger.

    PubMed

    Semwal, Ruchi Badoni; Semwal, Deepak Kumar; Combrinck, Sandra; Viljoen, Alvaro M

    2015-09-01

    Gingerols are the major pungent compounds present in the rhizomes of ginger (Zingiber officinale Roscoe) and are renowned for their contribution to human health and nutrition. Medicinal properties of ginger, including the alleviation of nausea, arthritis and pain, have been associated with the gingerols. Gingerol analogues are thermally labile and easily undergo dehydration reactions to form the corresponding shogaols, which impart the characteristic pungent taste to dried ginger. Both gingerols and shogaols exhibit a host of biological activities, ranging from anticancer, anti-oxidant, antimicrobial, anti-inflammatory and anti-allergic to various central nervous system activities. Shogaols are important biomarkers used for the quality control of many ginger-containing products, due to their diverse biological activities. In this review, a large body of available knowledge on the biosynthesis, chemical synthesis and pharmacological activities, as well as on the structure-activity relationships of various gingerols and shogaols, have been collated, coherently summarised and discussed. The manuscript highlights convincing evidence indicating that these phenolic compounds could serve as important lead molecules for the development of therapeutic agents to treat various life-threatening human diseases, particularly cancer. Inclusion of ginger or ginger extracts in nutraceutical formulations could provide valuable protection against diabetes, cardiac and hepatic disorders.

  20. Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity.

    PubMed

    Bate-Eya, Laurel T; Gierman, Hinco J; Ebus, Marli E; Koster, Jan; Caron, Huib N; Versteeg, Rogier; Dolman, M Emmy M; Molenaar, Jan J

    2017-04-01

    Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein.

  1. Nuclear factors that bind two regions important to transcriptional activity of the simian immunodeficiency virus long terminal repeat.

    PubMed Central

    Winandy, S; Renjifo, B; Li, Y; Hopkins, N

    1992-01-01

    Previous studies identified two regions in the U3 region of a molecular clone of simian immunodeficiency virus, SIVmac142, that are important to transcriptional activity under conditions of induction as well as basal-level expression (B. Renjifo, N. A. Speck, S. Winandy, N. Hopkins, and Y. Li, J. Virol. 64:3130-3134, 1990). One region includes the NF-kappa B binding site, while the other lies just 5' of this site between nucleotides -162 and -114 (the -162 to -114 region). The fact that the NF-kappa B site mutation attenuated transcriptional activity in uninduced T cells and fibroblasts where activated NF-kappa B would not be present suggested that a factor(s) other than NF-kappa B could be acting through this site. In this study, we have identified a factor which binds to a cis element overlapping the NF-kappa B site. This factor, which we call simian factor 3 (SF3), would play a role in regulation under conditions of basal level expression, whereas under conditions of induction, NF-kappa B would act via this region. SF3 may also bind to an element in the -162 to -114 region. In addition, we have identified two other factors that bind the -162 to -114 region. One, which we designated SF1, is a ubiquitous basal factor, and the other, SF2, is a T-cell-predominant phorbol myristate acetate-inducible factor. Through identification of nuclear factors that interact with the U3 region of the SIVmac142 long terminal repeat, we can gain insight into how this virus is transcriptionally regulated under conditions of basal-level expression as well as conditions of T-cell activation. Images PMID:1501272

  2. Terracidiphilus gabretensis gen. nov., sp. nov., an Abundant and Active Forest Soil Acidobacterium Important in Organic Matter Transformation

    PubMed Central

    García-Fraile, Paula; Benada, Oldrich; Cajthaml, Tomáš; Baldrian, Petr

    2015-01-01

    Understanding the activity of bacteria in coniferous forests is highly important, due to the role of these environments as a global carbon sink. In a study of the microbial biodiversity of montane coniferous forest soil in the Bohemian Forest National Park (Czech Republic), we succeeded in isolating bacterial strain S55T, which belongs to one of the most abundant operational taxonomic units (OTUs) in active bacterial populations, according to the analysis of RNA-derived 16S rRNA amplicons. The 16S rRNA gene sequence analysis showed that the species most closely related to strain S55T include Bryocella elongata SN10T (95.4% identity), Acidicapsa ligni WH120T (95.2% identity), and Telmatobacter bradus TPB6017T (95.0% identity), revealing that strain S55T should be classified within the phylum Acidobacteria, subdivision 1. Strain S55T is a rod-like bacterium that grows at acidic pH (3 to 6). Its phylogenetic, genotypic, phenotypic, and chemotaxonomic characteristics indicate that strain S55T corresponds to a new genus within the phylum Acidobacteria; thus, we propose the name Terracidiphilus gabretensis gen. nov., sp. nov. (strain S55T = NBRC 111238T = CECT 8791T). This strain produces extracellular enzymes implicated in the degradation of plant-derived biopolymers. Moreover, analysis of the genome sequence of strain S55T also reveals the presence of enzymatic machinery required for organic matter decomposition. Soil metatranscriptomic analyses found 132 genes from strain S55T being expressed in the forest soil, especially during winter. Our results suggest an important contribution of T. gabretensis S55T in the carbon cycle in the Picea abies coniferous forest. PMID:26546425

  3. The relative importance of respiratory water loss in scorpions is correlated with species habitat type and activity pattern.

    PubMed

    Gefen, Eran

    2011-01-01

    Scorpions exhibit some of the lowest recorded water loss rates compared with those of other terrestrial arthropods of similar body size. Evaporative water loss (EWL) includes cuticular transpiration and respiratory water loss (RWL) from gas exchange surfaces, that is, book lung lamellae. Estimated fractions of cuticular and respiratory losses currently available from the literature show considerable variation, at least partly as a result of differences in methodology. This study reports RWL rates and their relative importance in scorpions from two families (Buthidae and Scorpionidae), including both xeric and mesic species (or subspecies). Two of the included Buthidae were surface-dwelling species, and another inhabits empty burrows of other terrestrial arthropods. This experimental design enabled correlating RWL importance with scorpion phylogeny, habitat type, and/or homing behavior. Buthidae species exhibited significantly lower EWL rates compared with those of Scorpionidae, whereas effects of habitat type and homing behavior were not significant. Resting RWL rates were not significantly affected by scorpion phylogeny, but rates for the xeric species (totaling ~10% of EWL rates at 30°C) were significantly lower compared with those of mesic species. These lower RWL values were correlated with significantly lower H(2)O/CO(2) emission rates in xeric species. The experimental setup and ~24-h duration of each individual recording allowed estimating the effect of interspecific variation in activity on RWL proportions. The high respiratory losses in active hydrated Scorpio maurus fuscus, totaling 30% of EWL, suggest that behavioral discretion in this species is a more likely mechanism for body water conservation under stressful conditions when compared with the responses of other studied species.

  4. Sterol-dependent nuclear import of ORP1S promotes LXR regulated trans-activation of apoE

    SciTech Connect

    Lee, Sungsoo; Wang, Ping-Yuan; Jeong, Yangsik; Mangelsdorf, David J.; Anderson, Richard G.W.; Michaely, Peter

    2012-10-01

    Oxysterol binding protein related protein 1S (ORP1S) is a member of a family of sterol transport proteins. Here we present evidence that ORP1S translocates from the cytoplasm to the nucleus in response to sterol binding. The sterols that best promote nuclear import of ORP1S also activate the liver X receptor (LXR) transcription factors and we show that ORP1S binds to LXRs, promotes binding of LXRs to LXR response elements (LXREs) and specifically enhances LXR-dependent transcription via the ME.1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR-dependent gene transcription through select enhancer elements. -- Highlights: Black-Right-Pointing-Pointer ORP1S translocates to the nucleus in response to sterol binding. Black-Right-Pointing-Pointer The sterols that best promote nuclear import of ORP1S are LXR agonists. Black-Right-Pointing-Pointer ORP1S binds to LXRs, enhances binding of LXRs to LXREs and promotes LXR-dependent transcription of apoE.

  5. Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    Although serine proteases are important mediators of Mycobacterium tuberculosis (Mtb) virulence, there are currently no tools to selectively block or visualize members of this family of enzymes. Selective reporter substrates or activity-based probes (ABPs) could provide a means to monitor infection and response to therapy using imaging methods. Here, we use a combination of substrate selectivity profiling and focused screening to identify optimized reporter substrates and ABPs for the Mtb “Hydrolase important for pathogenesis 1” (Hip1) serine protease. Hip1 is a cell-envelope-associated enzyme with minimal homology to host proteases, making it an ideal target for probe development. We identified substituted 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarins as irreversible inhibitor scaffolds. Furthermore, we used specificity data to generate selective reporter substrates and to further optimize a selective chloroisocoumarin inhibitor. These new reagents are potentially useful in delineating the roles of Hip1 during pathogenesis or as diagnostic imaging tools for specifically monitoring Mtb infections. PMID:27739665

  6. TGF- β: an important mediator of allergic disease and a molecule with dual activity in cancer development.

    PubMed

    Tirado-Rodriguez, Belen; Ortega, Enrique; Segura-Medina, Patricia; Huerta-Yepez, Sara

    2014-01-01

    The transforming growth factor- β (TGF- β ) superfamily is a family of structurally related proteins that includes TGF- β , activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF- β superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF- β is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF- β receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF- β with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as "allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF- β is involved. Here, we review recent studies that suggest an important role for TGF- β in both allergic disease and cancer progression.

  7. TGF-β: An Important Mediator of Allergic Disease and a Molecule with Dual Activity in Cancer Development

    PubMed Central

    Tirado-Rodriguez, Belen; Segura-Medina, Patricia; Huerta-Yepez, Sara

    2014-01-01

    The transforming growth factor-β (TGF-β) superfamily is a family of structurally related proteins that includes TGF-β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF-β superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF-β is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF-β receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF-β with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as “allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF-β is involved. Here, we review recent studies that suggest an important role for TGF-β in both allergic disease and cancer progression. PMID:25110717

  8. Effect of Erica sp. honey against microorganisms of clinical importance: study of the factors underlying this biological activity.

    PubMed

    Feás, Xesus; Iglesias, Antonio; Rodrigues, Sandra; Estevinho, Leticia M

    2013-04-11

    This study aimed to determine the factors (phenolic compounds, flavonoids, sugars or H2O2) that contribute the most to the antimicrobial activity of heather honey samples against four yeasts and four bacteria with medical importance. To discard the effect of H2O2 in the antimicrobial activity, catalase was added. To evaluate the osmotic pressure's effect, artificial honey was also used. Phenolic compounds and flavonoids were determined and Pearson's correlation analysis was performed to assess whether these correlated with antimicrobial activity. The amount of phenolic compounds ranged from 630.89 ± 5.21 GAE kg-1 to 718.92 ± 4.41 GAE kg-1, while the flavonoids varied between 450.72 ± 5.67 CAE kg-1 and 673.98 ± 4.33 CAE kg-1. For the bacteria, the minimum inhibitory concentration (MIC) of the honey without catalase ranged from 1.01 ± 0.50% to 10.00 ± 4.72% and was between 2.00 ± 0.94% and 13.27 ± 5.23% for honey with catalase. Concerning the yeasts, the MICs was between 13.16 ± 4.08% and 20.00 ± 5.09% for honey without catalase and between 14.95 ± 4.16% and 25.67 ± 5.50% for honey with catalase. The elucidation of the antimicrobial factors and action mechanisms is essential for the correct use of honey in therapeutic applications.

  9. Sendai Virus and Simian Virus 5 Block Activation of Interferon-Responsive Genes: Importance for Virus Pathogenesis

    PubMed Central

    Didcock, L.; Young, D. F.; Goodbourn, S.; Randall, R. E.

    1999-01-01

    Sendai virus (SeV) is highly pathogenic for mice. In contrast, mice (including SCID mice) infected with simian virus 5 (SV5) showed no overt signs of disease. Evidence is presented that a major factor which prevented SV5 from productively infecting mice was its inability to circumvent the interferon (IFN) response in mice. Thus, in murine cells that produce and respond to IFN, SV5 protein synthesis was rapidly switched off. In marked contrast, once SeV protein synthesis began, it continued, even if the culture medium was supplemented with alpha/beta IFN (IFN-α/β). However, in human cells, IFN-α/β did not inhibit the replication of either SV5 or SeV once virus protein synthesis was established. To begin to address the molecular basis for these observations, the effects of SeV and SV5 infections on the activation of an IFN-α/β-responsive promoter and on that of the IFN-β promoter were examined in transient transfection experiments. The results demonstrated that (i) SeV, but not SV5, inhibited an IFN-α/β-responsive promoter in murine cells; (ii) both SV5 and SeV inhibited the activation of an IFN-α/β-responsive promoter in human cells; and (iii) in both human and murine cells, SeV was a strong inducer of the IFN-β promoter, whereas SV5 was a poor inducer. The ability of SeV and SV5 to inhibit the activation of IFN-responsive genes in human cells was confirmed by RNase protection experiments. The importance of these results in terms of paramyxovirus pathogenesis is discussed. PMID:10074164

  10. Genetics of flowering time in bread wheat Triticum aestivum: complementary interaction between vernalization-insensitive and photoperiod-insensitive mutations imparts very early flowering habit to spring wheat.

    PubMed

    Kumar, Sushil; Sharma, Vishakha; Chaudhary, Swati; Tyagi, Anshika; Mishra, Poonam; Priyadarshini, Anupama; Singh, Anupam

    2012-01-01

    Time to flowering in the winter growth habit bread wheat is dependent on vernalization (exposure to cold conditions) and exposure to long days (photoperiod). Dominant Vrn-1 (Vrn-A1, Vrn-B1 and Vrn-D1) alleles are associated with vernalization independent spring growth habit. The semidominant Ppd-D1a mutation confers photoperiod-insensitivity or rapid flowering in wheat under short day and long day conditions. The objective of this study was to reveal the nature of interaction between Vrn-1 and Ppd-D1a mutations (active alleles of the respective genes vrn-1 and Ppd-D1b). Twelve Indian spring wheat cultivars and the spring wheat landrace Chinese Spring were characterized for their flowering times by seeding them every month for five years under natural field conditions in New Delhi. Near isogenic Vrn-1 Ppd-D1 and Vrn-1 Ppd-D1a lines constructed in two genetic backgrounds were also phenotyped for flowering time by seeding in two different seasons. The wheat lines of Vrn-A1a Vrn-B1 Vrn-D1 Ppd-D1a, Vrn-A1a Vrn-B1 Ppd-D1a and Vrn-A1a Vrn-D1 Ppd-D1a (or Vrn-1 Ppd-D1a) genotypes flowered several weeks earlier than that of Vrn-A1a Vrn-B1 Vrn-D1 Ppd-D1b, Vrn-A1b Ppd-D1b and Vrn-D1 Ppd-D1b (or Vrn-1 Ppd-D1b) genotypes. The flowering time phenotypes of the isogenic vernalization-insensitive lines confirmed that Ppd-D1a hastened flowering by several weeks. It was concluded that complementary interaction between Vrn-1 and Ppd-D1a active alleles imparted super/very-early flowering habit to spring wheats. The early and late flowering wheat varieties showed differences in flowering time between short day and long day conditions. The flowering time in Vrn-1 Ppd-D1a genotypes was hastened by higher temperatures under long day conditions. The ambient air temperature and photoperiod parameters for flowering in spring wheat were estimated at 25°C and 12 h, respectively.

  11. Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB

    PubMed Central

    Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Jiang, Xia; Nakamura, Masato; Sasaki, Reina; Haga, Yuki; Shirasawa, Hiroshi; Yokosuka, Osamu

    2016-01-01

    Elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β are often observed in the sera of hepatitis B virus (HBV)-infected patients. It is well known that these cytokines activate nuclear factor-κB (NF-κB)-signaling, and are associated with endoplasmic reticulum (ER) stress. We investigated whether HBV or HBV X protein (HBx) enhanced the activation of NF-κB in the presence of TNF and/or IL-1β, and their effects on the expression of metabolic pathway-associated genes. We examined whether HBV or HBx enhanced cytokine-induced activation of NF-κB in hepatocytes, using a reporter assay, in the presence or absence of TNF and/or IL-1β. The expression of insulin-like growth factor binding protein 1 (IGFBP1), one of the NF-κB target genes was also examined. The expression of metabolic pathway-associated genes in HepG2 and HepG2.2.15 cells in the presence or absence of TNF was evaluated by RT-qPCR. Human hepatocytes expressed TNF receptors and IL-1 receptors. NF-κB was activated by cooperation between HBx and TNF in human hepatocytes. We observed IGFBP1 expression in HBV infection and that a number of metabolic pathway-associated genes were upregulated in HepG2.2.15 cells, compared with HepG2 cells with or without TNF treatment. We observed the cooperative effects of HBV and TNF which enhanced the activation of NF-κB as well as upregulated the expression of metabolic pathway-associated genes in hepatocytes. These effects may be important in the development of HBV-associated metabolic syndrome. PMID:27315566

  12. Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB.

    PubMed

    Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Jiang, Xia; Nakamura, Masato; Sasaki, Reina; Haga, Yuki; Shirasawa, Hiroshi; Yokosuka, Osamu

    2016-08-01

    Elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β are often observed in the sera of hepatitis B virus (HBV)-infected patients. It is well known that these cytokines activate nuclear factor-κB (NF-κB)-signaling, and are associated with endoplasmic reticulum (ER) stress. We investigated whether HBV or HBV X protein (HBx) enhanced the activation of NF-κB in the presence of TNF and/or IL-1β, and their effects on the expression of metabolic pathway‑associated genes. We examined whether HBV or HBx enhanced cytokine-induced activation of NF-κB in hepatocytes, using a reporter assay, in the presence or absence of TNF and/or IL-1β. The expression of insulin-like growth factor binding protein 1 (IGFBP1), one of the NF-κB target genes was also examined. The expression of metabolic pathway-associated genes in HepG2 and HepG2.2.15 cells in the presence or absence of TNF was evaluated by RT-qPCR. Human hepatocytes expressed TNF receptors and IL-1 receptors. NF-κB was activated by cooperation between HBx and TNF in human hepatocytes. We observed IGFBP1 expression in HBV infection and that a number of metabolic pathway-associated genes were upregulated in HepG2.2.15 cells, compared with HepG2 cells with or without TNF treatment. We observed the cooperative effects of HBV and TNF which enhanced the activation of NF-κB as well as upregulated the expression of metabolic pathway-associated genes in hepatocytes. These effects may be important in the development of HBV-associated metabolic syndrome.

  13. Identification and antifungal activity of novel organic compounds found in cuticular and internal lipids of medically important flies.

    PubMed

    Gołębiowski, Marek; Cerkowniak, Magdalena; Urbanek, Aleksandra; Dawgul, Małgorzata; Kamysz, Wojciech; Boguś, Mieczysława I; Stepnowski, Piotr

    2015-01-01

    Novel organic compounds found in the cuticular and internal lipids of medically important flies were identified. Uracil, 9-tricosene, 1-oleoyl glycerol, dimethyl suberate and butyl stearate were tested for their potential antifungal activity. Minimal inhibitory concentrations of the compounds against reference strains of fungi were determined. Uracil and dimethyl suberate slightly inhibited the growth of entomopathogenic fungi. The cuticular and internal lipids of Calliphora vicina, Calliphora vomitoria, Sarcophaga carnaria and Musca domestica were studied by gas chromatography (GC) combined with mass spectrometry (GC/MS). A comparison of the lipid extracts between the preimaginal and mature stages showed adults flies contained a higher total content of the identified components. Furthermore, their amounts distinctly predominated in the internal lipids of all the species. The amount of 9-tricosene was the highest in adults of C. vicina, while the larvae and pupae had a definitively lower amount of this compound. Uracil was found to be the most abundant component in extracts obtained from C. vomitoria especially in the internal lipids of adults. 1-oleoyl glycerol was detected in all of the examined species of flies. It was most abundant in the internal extracts isolated from the larvae of C. vicina and the pupae of C. vomitoria. Suberic acid dimethyl ester was found in the larval and pupal internal lipids of C. vicina and S. carnaria in low amounts. Butyl stearate was identified only in the internal lipids of the larvae and adults of houseflies.

  14. Structure-activity relationship of ochratoxin A and synthesized derivatives: importance of amino acid and halogen moiety for cytotoxicity.

    PubMed

    Rottkord, Ulrike; Röhl, Christopher; Ferse, Ines; Schulz, Marie-Christin; Rückschloss, Uwe; Gekle, Michael; Schwerdt, Gerald; Humpf, Hans-Ulrich

    2017-03-01

    The enigma why the mycotoxin ochratoxin A (OTA) impairs cell and organ function is still not solved. However, an interaction with target molecules is a prerequisite for any observed adverse effect. This interaction depends on characteristics of the target molecule as well as on the OTA molecule itself. OTA has different structural moieties which may be relevant for these interrelations including a halogen (chlorine) and an amino acid group (phenylalanine). To test their importance for the impact of OTA, detailed structure-activity studies with various OTA derivatives were performed. For this, 23 OTA derivatives were available, which were modified by either an exchange of the halogen moiety against another halogen (fluorine, iodine or bromine) or by the amino acid moiety against another one (tyrosine or alanine) or a combination of both. Additionally, the configuration of the 3R carbon atom was changed to 3S. These derivatives were tested in human renal cells for their ability to induce cell death (cytotoxicity, apoptosis, necrosis), their impact on collagen protein secretion and for their influence on gene expression. It turned out that the substitution of the amino acid moiety against tyrosine or alanine almost completely prevented the adverse effects of OTA. The exchange of the halogen moiety had minor effects and the inversion of the stereochemistry at C3 did not prevent the effects of OTA. Therefore, we conclude that the amino acid moiety of OTA is indispensable for the interaction of OTA with its target molecules.

  15. Alumoxane/ferroxane nanoparticles for the removal of viral pathogens: the importance of surface functionality to nanoparticle activity.

    PubMed

    Maguire-Boyle, Samuel J; Liga, Michael V; Li, Qilin; Barron, Andrew R

    2012-09-21

    A bi-functional nano-composite coating has been created on a porous Nomex® fabric support as a trap for aspirated virus contaminated water. Nomex® fabric was successively dip-coated in solutions containing cysteic acid functionalized alumina (alumoxane) nanoparticles and cysteic acid functionalized iron oxide (ferroxane) nanoparticles to form a nanoparticle coated Nomex® (NPN) fabric. From SEM and EDX the nanoparticle coating of the Nomex® fibers is uniform, continuous, and conformal. The NPN was used as a filter for aspirated bacteriophage MS2 viruses using end-on filtration. All measurements were repeated to give statistical reliability. The NPN fabrics show a large decrease as compared to Nomex® alone or alumoxane coated Nomex®. An increase in the ferroxane content results in an equivalent increase in virus retention. This suggests that it is the ferroxane that has an active role in deactivating and/or binding the virus. Heating the NPN to 160 °C results in the loss of cysteic acid functional groups (without loss of the iron nanoparticle's core structure) and the resulting fabric behaves similar to that of untreated Nomex®, showing that the surface functionalization of the nanoparticles is vital for the surface collapse of aspirated water droplets and the absorption and immobilization of the MS2 viruses. Thus, for virus immobilization, it is not sufficient to have iron oxide nanoparticles per se, but the surface functionality of a nanoparticle is vitally important in ensuring efficacy.

  16. Generation of interleukin-6 receptor antagonists by molecular-modeling guided mutagenesis of residues important for gp130 activation.

    PubMed Central

    Savino, R; Lahm, A; Salvati, A L; Ciapponi, L; Sporeno, E; Altamura, S; Paonessa, G; Toniatti, C; Ciliberto, G

    1994-01-01

    Interleukin-6 (IL-6) drives the sequential assembly of a receptor complex formed by the IL-6 receptor (IL-6R alpha) and the signal transducing subunit, gp130. A model of human IL-6 (hIL-6) was constructed by homology using the structure of bovine granulocyte colony stimulating factor. The modeled cytokine was predicted to interact sequentially with the cytokine binding domains of IL-6R alpha and gp130 bridging them in a way similar to that of the interaction between growth hormone and its homodimeric receptor. Several residues on helices A and C which were predicted as contact points between IL-6 and gp130 and therefore essential for IL-6 signal transduction, were subjected to site-directed mutagenesis individually or in combined form. Interestingly, while single amino acid changes never produced major alterations in IL-6 bioactivity, a subset of double mutants of Y31 and G35 showed a considerable reduction of biological activity and were selectively impaired from associating with gp130 in binding assays in vitro, while they maintained wild-type affinity towards hIL-6-R alpha. More importantly, we demonstrated the antagonistic effect of mutant Y31D/G35F versus wild-type IL-6. Images PMID:7511100

  17. The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury.

    PubMed

    Sevelsted Møller, Linda; Fialla, Annette Dam; Schierwagen, Robert; Biagini, Matteo; Liedtke, Christian; Laleman, Wim; Klein, Sabine; Reul, Winfried; Koch Hansen, Lars; Rabjerg, Maj; Singh, Vikrant; Surra, Joaquin; Osada, Jesus; Reinehr, Roland; de Muckadell, Ove B Schaffalitzky; Köhler, Ralf; Trebicka, Jonel

    2016-06-29

    The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury.

  18. The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury

    PubMed Central

    Sevelsted Møller, Linda; Fialla, Annette Dam; Schierwagen, Robert; Biagini, Matteo; Liedtke, Christian; Laleman, Wim; Klein, Sabine; Reul, Winfried; Koch Hansen, Lars; Rabjerg, Maj; Singh, Vikrant; Surra, Joaquin; Osada, Jesus; Reinehr, Roland; de Muckadell, Ove B. Schaffalitzky; Köhler, Ralf; Trebicka, Jonel

    2016-01-01

    The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury. PMID:27354175

  19. An Important Natural Genetic Resource of Oreochromis niloticus (Linnaeus, 1758) Threatened by Aquaculture Activities in Loboi Drainage, Kenya

    PubMed Central

    Ndiwa, Titus Chemandwa; Nyingi, Dorothy Wanja; Agnese, Jean-François

    2014-01-01

    The need to improve food security in Africa through culture of tilapias has led to transfer of different species from their natural ranges causing negative impacts on wild fish genetic resources. Loboi swamp in Kenya is fed by three hot springs: Lake Bogoria Hotel, Chelaba and Turtle Springs, hosting natural populations of Oreochromis niloticus. The present study aimed at better genetic characterization of these threatened populations. Partial mtDNA sequences of the D-loop region and variations at 16 microsatellite loci were assessed in the three hot spring populations and compared with three other natural populations of O. niloticus in the region. Results obtained indicated that the hot spring populations had mitochondrial and nuclear genetic variability similar to or higher than the large closely related populations. This may be attributed to the perennial nature of the hot springs, which do not depend on rainfall but rather receive permanent water supply from deep aquifers. The study also revealed that gene flow between the three different hot spring populations was sufficiently low thus allowing their differentiation. This differentiation was unexpected considering the very close proximity of the springs to each other. It is possible that the swamp creates a barrier to free movement of fish from one spring to the other thereby diminishing gene flow. Finally, the most surprising and worrying results were that the three hot spring populations are introgressed by mtDNA genes of O. leucostictus, while microsatellite analysis suggested that some nuclear genes may also have crossed the species barrier. It is very likely that the recent intensification of aquaculture activities in the Loboi drainage may be responsible for these introgressions. Taking into account the importance of these new genetic resources, protection and management actions of the Loboi swamp should be accorded top priority to prevent the loss of these spring populations. PMID:25222491

  20. An important natural genetic resource of Oreochromis niloticus (Linnaeus, 1758) threatened by aquaculture activities in Loboi drainage, Kenya.

    PubMed

    Ndiwa, Titus Chemandwa; Nyingi, Dorothy Wanja; Agnese, Jean-François

    2014-01-01

    The need to improve food security in Africa through culture of tilapias has led to transfer of different species from their natural ranges causing negative impacts on wild fish genetic resources. Loboi swamp in Kenya is fed by three hot springs: Lake Bogoria Hotel, Chelaba and Turtle Springs, hosting natural populations of Oreochromis niloticus. The present study aimed at better genetic characterization of these threatened populations. Partial mtDNA sequences of the D-loop region and variations at 16 microsatellite loci were assessed in the three hot spring populations and compared with three other natural populations of O. niloticus in the region. Results obtained indicated that the hot spring populations had mitochondrial and nuclear genetic variability similar to or higher than the large closely related populations. This may be attributed to the perennial nature of the hot springs, which do not depend on rainfall but rather receive permanent water supply from deep aquifers. The study also revealed that gene flow between the three different hot spring populations was sufficiently low thus allowing their differentiation. This differentiation was unexpected considering the very close proximity of the springs to each other. It is possible that the swamp creates a barrier to free movement of fish from one spring to the other thereby diminishing gene flow. Finally, the most surprising and worrying results were that the three hot spring populations are introgressed by mtDNA genes of O. leucostictus, while microsatellite analysis suggested that some nuclear genes may also have crossed the species barrier. It is very likely that the recent intensification of aquaculture activities in the Loboi drainage may be responsible for these introgressions. Taking into account the importance of these new genetic resources, protection and management actions of the Loboi swamp should be accorded top priority to prevent the loss of these spring populations.

  1. Beyond lipids, pharmacological PPARalpha activation has important effects on amino acid metabolism as studied in the rat.

    PubMed

    Sheikh, Kashif; Camejo, Germán; Lanne, Boel; Halvarsson, Torbjörn; Landergren, Marie Rydén; Oakes, Nicholas D

    2007-04-01

    PPARalpha agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARalpha agonist WY 14,643 (30 micromol x kg(-1) x day(-1) for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARalpha activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.

  2. Efficacy of Resistance to Francisella Imparted by ITY/NRAMP/SLC11A1 Depends on Route of Infection.

    PubMed

    Powell, Daniel A; Frelinger, Jeffrey A

    2017-01-01

    Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1(Gly169), which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1(Asp169), that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1(Gly169) (B6-Slc11a1(G169) ) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis. We examined the host cell response and replication of Francisella in B6-Slc11a1(G169) mice. Bone marrow-derived macrophages from either B6-Slc11a1(G169) or B6 mice were both effectively invaded by Francisella live vaccine strain (LVS). However, at 16 hours post-infection (hpi), the number of LVS bacteria recovered from B6 macrophages had increased roughly 100-fold, while in B6-Slc11a1(G169) mice the number decreased 10-fold. When the mice were challenged intranasally (i.n.) B6 mice lost significant amounts (~15%) of weight, where as B6-Slc11a1(G169) mice lost no weight. Three days after infection in B6-Slc11a1(G169) mice, we failed to recover viable Francisella from the lungs, livers, or spleens. By contrast, B6 mice had bacterial burdens approaching 1 × 10(6) CFU/organ in all three organs. To further examine the degree of resistance imparted by Slc11a1(Gly169) expression, we challenged mice deficient in TLR2, TLR4, and TLR9, but expressing the functional Slc11a1 (B6-Slc11a1(G169)Tlr2/4/9(-/-) ). Surprisingly, B6-Slc11a1(G169)Tlr2/4/9(-/-) mice had no notable weight loss. Eighty percent of B6-Slc11a1(G169)Tlr2/4/9(-)(/)(-) mice yielded no detectable Francisella in any organ tested. Additionally, Slc11a1(G169) produced little detectable cytokine either in the lung or serum compared to B6 mice. Mice expressing Slc11a1(Gly169) survived even high doses (~80 LD50) of LVS inoculation. These data taken together serve to highlight

  3. Efficacy of Resistance to Francisella Imparted by ITY/NRAMP/SLC11A1 Depends on Route of Infection

    PubMed Central

    Powell, Daniel A.; Frelinger, Jeffrey A.

    2017-01-01

    Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1Gly169, which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1Asp169, that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1Gly169 (B6-Slc11a1G169) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis. We examined the host cell response and replication of Francisella in B6-Slc11a1G169 mice. Bone marrow-derived macrophages from either B6-Slc11a1G169 or B6 mice were both effectively invaded by Francisella live vaccine strain (LVS). However, at 16 hours post-infection (hpi), the number of LVS bacteria recovered from B6 macrophages had increased roughly 100-fold, while in B6-Slc11a1G169 mice the number decreased 10-fold. When the mice were challenged intranasally (i.n.) B6 mice lost significant amounts (~15%) of weight, where as B6-Slc11a1G169 mice lost no weight. Three days after infection in B6-Slc11a1G169 mice, we failed to recover viable Francisella from the lungs, livers, or spleens. By contrast, B6 mice had bacterial burdens approaching 1 × 106 CFU/organ in all three organs. To further examine the degree of resistance imparted by Slc11a1Gly169 expression, we challenged mice deficient in TLR2, TLR4, and TLR9, but expressing the functional Slc11a1 (B6-Slc11a1G169Tlr2/4/9−/−). Surprisingly, B6-Slc11a1G169Tlr2/4/9−/− mice had no notable weight loss. Eighty percent of B6-Slc11a1G169Tlr2/4/9−/− mice yielded no detectable Francisella in any organ tested. Additionally, Slc11a1G169 produced little detectable cytokine either in the lung or serum compared to B6 mice. Mice expressing Slc11a1Gly169 survived even high doses (~80 LD50) of LVS inoculation. These data taken together serve to highlight that functional Slc11a1Gly169 can

  4. 75 FR 5055 - Taking and Importing Marine Mammals; U.S. Navy's Atlantic Fleet Active Sonar Training (AFAST)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    .... Navy's Atlantic Fleet Active Sonar Training (AFAST) AGENCY: National Marine Fisheries Service (NMFS..., testing, and evaluation (RDT&E) activities to be conducted within the Atlantic Fleet Active Sonar Training... side mine hunting sonar in the AFAST Study area, which reduces use from 4474 hours annually to 0....

  5. Cyber Electromagnetic Activities within the Mission Command Warfighting Function: Why is it Important and What is the Capability?

    DTIC Science & Technology

    2013-12-13

    33 CEMA and the Mission Command Warfighting Function...Army Doctrine Publication ADRP Army Doctrine Reference Publication CEMA Cyber-Electromagnetic Activities DOD Department of Defense EMSO Electronic

  6. The Importance of Physical Fitness versus Physical Activity for Coronary Artery Disease Risk Factors: A Cross-Sectional Analysis.

    ERIC Educational Resources Information Center

    Young, Deborah Rohm; Steinhardt, Mary A.

    1993-01-01

    This cross-sectional study examined relationships among physical fitness, physical activity, and risk factors for coronary artery disease (CAD) in male police officers. Data from screenings and physical fitness assessments indicated physical activity must be sufficient to influence fitness before obtaining statistically significant risk-reducing…

  7. The Seeds of Learning: Young Children Develop Important Skills through Their Gardening Activities at a Midwestern Early Education Program

    ERIC Educational Resources Information Center

    Miller, Dana L.

    2007-01-01

    Using teachers as co-researchers to collect and analyze data, this case study explored preschool and kindergarteners' learning when they were engaged in hands-on activities in the garden and greenhouse areas of a model outdoor classroom. Key findings suggest that when young children are participating in garden and greenhouse activities they are:…

  8. Assessing the Importance of Social and Environmental Supports for Leisure-Time Physical Activity in a Unique Socio-Cultural and Geographical Context

    ERIC Educational Resources Information Center

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

    2010-01-01

    Researchers have found important differences among population sub-groups when considering their "determinants of physical activity". The health of Francophones and Northern Ontario residents in Canada has been assessed as relatively poorer than the general population. Understanding the determinants of physical activity in these…

  9. The importance of activity-based methods in radiology and the technology that now makes this possible.

    PubMed

    Monge, Paul

    2006-01-01

    Activity-based methods serve as a dynamic process that has allowed many other industries to reduce and control their costs, increase productivity, and streamline their processes while improving product quality and service. The method could serve the healthcare industry in an equally beneficial way. Activity-based methods encompass both activity based costing (ABC) and activity-based management (ABM). ABC is a cost management approach that links resource consumption to activities that an enterprise performs, and then assigns those activities and their associated costs to customers, products, or product lines. ABM uses the resource assignments derived in ABC so that operation managers can improve their departmental processes and workflows. There are three fundamental problems with traditional cost systems. First, traditional systems fail to reflect the underlying diversity of work taking place within an enterprise. Second, it uses allocations that are, for the most part, arbitrary Single step allocations fail to reflect the real work-the activities being performed and the associate resources actually consumed. Third, they only provide a cost number that, standing alone, does not provide any guidance on how to improve performance by lowering cost or enhancing throughput.

  10. NADPH Oxidase-Dependent NLRP3 Inflammasome Activation and its Important Role in Lung Fibrosis by Multiwalled Carbon Nanotubes.

    PubMed

    Sun, Bingbing; Wang, Xiang; Ji, Zhaoxia; Wang, Meiying; Liao, Yu-Pei; Chang, Chong Hyun; Li, Ruibin; Zhang, Haiyuan; Nel, André E; Xia, Tian

    2015-05-06

    The purpose of this paper is to elucidate the key role of NADPH oxidase in NLRP3 inflammasome activation and generation of pulmonary fibrosis by multi-walled carbon nanotubes (MWCNTs). Although it is known that oxidative stress plays a role in pulmonary fibrosis by single-walled CNTs, the role of specific sources of reactive oxygen species, including NADPH oxidase, in inflammasome activation remains to be clarified. In this study, three long aspect ratio (LAR) materials (MWCNTs, single-walled carbon nanotubes, and silver nanowires) are used to compare with spherical carbon black and silver nanoparticles for their ability to trigger oxygen burst activity and NLRP3 assembly. All LAR materials but not spherical nanoparticles induce robust NADPH oxidase activation and respiratory burst activity in THP-1 cells, which are blunted in p22(phox) -deficient cells. The NADPH oxidase is directly involved in lysosomal damage by LAR materials, as demonstrated by decreased cathepsin B release and IL-1β production in p22(phox) -deficient cells. Reduced respiratory burst activity and inflammasome activation are also observed in bone marrow-derived macrophages from p47(phox) -deficient mice. Moreover, p47(phox) -deficient mice have reduced IL-1β production and lung collagen deposition in response to MWCNTs. Lung fibrosis is also suppressed by N-acetyl-cysteine in wild-type animals exposed to MWCNTs.

  11. Nematicidal and antimicrobial activities of methanol extracts of 17 plants, of importance in ethnopharmacology, obtained from the Arabian Peninsula

    PubMed Central

    Al-Marby, Adel; Ejike, Chukwunonso ECC; Nasim, Muhammad Jawad; Awadh-Ali, Nasser A; Al-badani, Rwaida A; Alghamdi, Ghanem MA; Jacob, Claus

    2016-01-01

    Aim/Background: The development of resistance to synthetic drugs by target organisms is a major challenge facing medicine, yet locked within plants are phytochemicals used in herbal medicine (especially in the Arabian Peninsula) that may find application in this regard. In pursuit of unlocking these “hidden treasures,” the methanol extracts of leaves, aerial parts, fruits, and resins of 17 plants used in the Arabian Peninsula were screened for antimicrobial activities. Materials and Methods: The nematicidal, antibacterial, and antifungal activities were determined using appropriate assays. Steinernema feltiae, Staphylococcus carnosus, Escherichia coli, and Saccharomyces cerevisiae were used as test organisms. Concentrations of the extracts ranging from 0.5 to 20 mg/ml were tested and appropriate statistical tests performed on the data generated. Results: The results show that extracts from Solanum incanum, Chenopodium murale, Commiphora myrrha, Anthemis nobilis, and Achillea biebersteinii were the most active and had very high activities against two or more of the test organisms at low concentrations. Extracts of the leaves of S. incanum and resins of Ferula asafoetida were the most active nematicides, with significant activity at 0.5 mg/ml. Extracts of C. myrrha and C. murale had the most active antibacterial activity with inhibition zones of 12-15 mm and minimum inhibitory concentrations (MICs) of 2.5 mg/ml for both bacteria. Extracts of the leaves of A. biebersteinii were the most active fungicide, giving an MIC of 1.5 mg/ml. Conclusion: The results validate the use of these plants in ethnopharmacology, and open new vistas of opportunities for the development of cheap but effective agents that may be useful against infectious diseases. PMID:27104031

  12. Tyrosine residues at the carboxyl terminus of Vav1 play an important role in regulation of its biological activity.

    PubMed

    Lazer, Galit; Pe'er, Liron; Farago, Marganit; Machida, Kazuya; Mayer, Bruce J; Katzav, Shulamit

    2010-07-23

    The guanine nucleotide exchange factor (GEF) Vav1 is an essential signal transducer protein in the hematopoietic system, where it is expressed physiologically. It is also involved in several human malignancies. Tyrosine phosphorylation at the Vav1 amino terminus plays a central role in regulating its activity; however, the role of carboxyl terminal tyrosine residues is unknown. We found that mutation of either Tyr-826 (Y826F) or Tyr-841 (Y841F) to phenylalanine led to loss of Vav1 GEF activity. When these Vav1 mutants were ectopically expressed in pancreatic cancer cells lacking Vav1, they failed to induce growth in agar, indicating loss of transforming potential. Furthermore, although Y841F had no effect on Vav1-stimulated nuclear factor of activated T cells (NFAT) activity, Y826F doubled NFAT activity when compared with Vav1, suggesting that Tyr-826 mediates an autoinhibitory effect on NFAT activity. SH2 profiling revealed that Shc, Csk, Abl, and Sap associate with Tyr-826, whereas SH2-B, Src, Brk, GTPase-activating protein, and phospholipase C-gamma associate with Tyr-841. Although the mutations in the Tyr-826 and Tyr-841 did not affect the binding of the carboxyl SH3 of Vav1 to other proteins, binding to several of the proteins identified by the SH2 profiling was lost. Of interest is Csk, which associates with wild-type Vav1 and Y841F, yet it fails to associate with Y826F, suggesting that loss of binding between Y826F and Csk might relieve an autoinhibitory effect, leading to increased NFAT. Our data indicate that GEF activity is critical for the function of Vav1 as a transforming protein but not for NFAT stimulation. The association of Vav1 with other proteins, detected by SH2 profiling, might affect other Vav1-dependent activities, such as NFAT stimulation.

  13. The importance of culturally meaningful activity for health benefits among older Korean immigrant living in the United States

    PubMed Central

    Kim, Junhyoung; Kim, May; Han, Areum; Chin, Seungtae

    2015-01-01

    Research indicates that participation in culturally meaningful activity is beneficial for immigrants’ health and well-being, yet older Korean immigrants struggle with accepting new cultural perspectives, which can negatively affect their health and well-being. Using in-depth interviews, this study was designed to capture the value of culturally meaningful activities for health among older Korean immigrants. Three themes were identified: (a) improved psychological well-being, (b) enhanced positive emotions and feelings, and (c) social connections developed with others. The findings suggest that by engaging in various culturally meaningful activities, older Korean immigrants gain a sense of social, cultural, and psychological significance in life. This study also provided evidence that older Korean immigrants maintain and develop their cultural identity through culturally meaningful activities. PMID:26084272

  14. In vitro antibacterial activity of chitosan and chitosan oligosaccharide lactate against important gram negative warmwater fish pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: The antibacterial activities of chitosan (CS) and its derivative chitosan oligosaccharide lactate (COL) were evaluated against Aeromonas hydrophila, Edwardsiella ictaluri and Flavobacterium columnare, three highly pathogenic bacteria of warmwater finfish. Methods and Results: The kinetics of ce...

  15. The 1911 M ~6.6 Calaveras earthquake: Source parameters and the role of static, viscoelastic, and dynamic coulomb stress changes imparted by the 1906 San Francisco earthquake

    USGS Publications Warehouse

    Doser, D.I.; Olsen, K.B.; Pollitz, F.F.; Stein, R.S.; Toda, S.

    2009-01-01

    The occurrence of a right-lateral strike-slip earthquake in 1911 is inconsistent with the calculated 0.2-2.5 bar static stress decrease imparted by the 1906 rupture at that location on the Calaveras fault, and 5 yr of calculated post-1906 viscoelastic rebound does little to reload the fault. We have used all available first-motion, body-wave, and surface-wave data to explore possible focal mechanisms for the 1911 earthquake. We find that the event was most likely a right-lateral strikeslip event on the Calaveras fault, larger than, but otherwise resembling, the 1984 Mw 6.1 Morgan Hill earthquake in roughly the same location. Unfortunately, we could recover no unambiguous surface fault offset or geodetic strain data to corroborate the seismic analysis despite an exhaustive archival search. We calculated the static and dynamic Coulomb stress changes for three 1906 source models to understand stress transfer to the 1911 site. In contrast to the static stress shadow, the peak dynamic Coulomb stress imparted by the 1906 rupture promoted failure at the site of the 1911 earthquake by 1.4-5.8 bar. Perhaps because the sample is small and the aftershocks are poorly located, we find no correlation of 1906 aftershock frequency or magnitude with the peak dynamic stress, although all aftershocks sustained a calculated dynamic stress of ???3 bar. Just 20 km to the south of the 1911 epicenter, we find that surface creep of the Calaveras fault at Hollister paused for ~17 yr after 1906, about the expected delay for the calculated static stress drop imparted by the 1906 earthquake when San Andreas fault postseismic creep and viscoelastic relaxation are included. Thus, the 1911 earthquake may have been promoted by the transient dynamic stresses, while Calaveras fault creep 20 km to the south appears to have been inhibited by the static stress changes.

  16. Developmental experiences during extracurricular activities and Australian adolescents' self-concept: particularly important for youth from disadvantaged schools.

    PubMed

    Blomfield, Corey J; Barber, Bonnie L

    2011-05-01

    Extracurricular activities provide adolescents with a number of positive personal and interpersonal developmental experiences. This study investigated whether developmental experiences that occurred during extracurricular activities were linked to a more positive self-concept for Australian adolescents, and whether this link was particularly salient for youth from disadvantaged schools. Adolescents (N = 1,504, 56% Female) from 26 diverse high schools across Western Australia were surveyed. The findings revealed that adolescents from low socio-economic status schools who participated in extracurricular activities had a more positive general self-worth and social self-concept than adolescents from similar socio-economic schools who did not participate in any extracurricular activities. Furthermore, the positive developmental experiences that occurred during extracurricular activities predicted a more positive general self-worth and social and academic self-concept, and this link was stronger for youth from low SES schools. These findings suggest that the developmental experiences afforded by extracurricular activities may foster positive adolescent development.

  17. RAC1 GTPase plays an important role in γ-irradiation induced G2/M checkpoint activation

    PubMed Central

    2012-01-01

    Introduction In response to gamma-irradiation (IR)-induced double-strand DNA breaks, cells undergo cell-cycle arrest, allowing time for DNA repair before reentering the cell cycle. G2/M checkpoint activation involves activation of ataxia telangiectasia mutated (ATM)/ATM- and rad3-related (ATR) kinases and inhibition of Cdc25 phosphatases, resulting in inhibition of Cdc2 kinase and subsequent G2/M cell-cycle arrest. Previous studies from our laboratory showed that the G2/M checkpoint activation after IR exposure of MCF-7 breast cancer cells is dependent on the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signaling. In the present studies, we investigated the role of Ras-related C3 botulinum toxin substrate 1 (Rac1) guanosine triphosphatase (GTPase) in IR-induced G2/M checkpoint response and ERK1/2 activation, as well as in cell survival after IR. Methods With Rac1-specific inhibitor, dominant negative mutant Rac1 (N17Rac1) and specific small interfering RNA, the effect of Rac1 on IR-induced G2/M checkpoint response and ERK1/2 activation was examined in human breast cancer cells. In addition, the effect of Rac1 on cell survival after irradiation was assessed by using Rac1-specific inhibitor. Results IR exposure of MCF-7 breast cancer cells was associated with a marked activation of Rac1 GTPase. Furthermore, inhibition of Rac1 by using specific inhibitor, dominant-negative Rac1 mutant, or specific siRNA resulted in attenuation of IR-induced G2/M arrest and concomitant diminution of IR-induced activation of ATM, ATR, Chk1, and Chk2 kinases, as well as phosphorylation of Cdc2-Tyr15. Moreover, Rac1 inhibition or decreased Rac1 expression also abrogated IR-induced phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) and ERK1/2. Ultimately, inhibition of Rac1 markedly increased cellular sensitivity to IR exposure, which involves induction of apoptosis. Conclusion Studies in this report suggest that Rac1 GTPase plays an

  18. Federal environmental standards of potential importance to operations and activities at US Department of Energy sites. Draft

    SciTech Connect

    Fowler, K.M.; Bilyard, G.R.; Davidson, S.A.; Jonas, R.J.; Joseph, J.

    1993-06-01

    The US Department of Energy (DOE) is now engaged in a program of environmental restoration nationwide across its 45 sites. It is also bringing its facilities into compliance with environmental regulations, decontaminating and decommissioning unwanted facilities, and constructing new waste management facilities. One of the most difficult questions that DOE must face in successfully remediating its inactive waste sites, decontaminating and decommissioning its inactive facilities, and operating its waste management facilities is: ``What criteria and standards should be met?`` Acceptable standards or procedures for determining standards will assist DOE in its conduct of ongoing waste management and pending cleanup activities by helping to ensure that those activities are conducted in compliance with applicable laws and regulations and are accepted by the regulatory community and the public. This document reports on the second of three baseline activities that are being conducted as prerequisites to either the development of quantitative standards that could be used by DOE, or consistent procedures for developing such standards. The first and third baseline activities are also briefly discussed in conjunction with the second of the three activities.

  19. PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.

    PubMed

    Sancho, Veronica; Berna, Marc J; Thill, Michelle; Jensen, R T

    2011-12-01

    The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal (GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin (CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA was present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ's direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth).

  20. PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades

    PubMed Central

    Sancho, Veronica; Berna, Marc J.; Thill, Michelle; Jensen, R. T.

    2011-01-01

    The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal(GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin(CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA were present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCKA-receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125FAK and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ’s direct association with AKT, RafA, RafC and Lyn. These results show for the first time PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth). PMID:21810446

  1. Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection.

    PubMed

    Raaben, Matthijs; Einerhand, Alexandra W C; Taminiau, Lucas J A; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis A M; Rossen, John W A

    2007-06-07

    Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.

  2. Bimetallic nanoalloys in heterogeneous catalysis of industrially important reactions: synergistic effects and structural organization of active components

    NASA Astrophysics Data System (ADS)

    Ellert, O. G.; Tsodikov, M. V.; Nikolaev, S. A.; Novotortsev, V. M.

    2014-08-01

    The review is concerned with correlations between the synergistic effects and structural organization of the surface of bimetallic alloys that are used as active components of catalysts for selective hydrogenation of organic compounds and for CO oxidation in hydrogen-rich mixtures. Studies on the preparation of novel highly efficient catalysts using modern theoretical approaches, computer-assisted molecular design and original synthetic procedures are considered. It is shown that introduction of the second metal into the monometallic catalyst and subsequent formation of alloy particles with modified structure of the surface and near-surface layers leads to nonadditive enhancement of catalytic activity and/or selectivity. The bibliography includes 203 references.

  3. The Importance of Motor Functional Levels from the Activity Limitation Perspective of ICF in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Mutlu, Akmer

    2010-01-01

    Our purpose in this study was to evaluate performance and capacity as defined by Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) from the "activity limitation" perspective of International Classification of Functioning, Disability, and Health (ICF) and to investigate the relationship between the…

  4. Chaperone activities of bovine and camel beta-caseins: Importance of their surface hydrophobicity in protection against alcohol dehydrogenase aggregation.

    PubMed

    Barzegar, Abolfazl; Yousefi, Reza; Sharifzadeh, Ahmad; Dalgalarrondo, Michèle; Chobert, Jean-Marc; Ganjali, Mohammad Reza; Norouzi, Parviz; Ehsani, Mohammad Reza; Niasari-Naslaji, Amir; Saboury, Ali Akbar; Haertlé, Thomas; Moosavi-Movahedi, Ali Akbar

    2008-05-01

    Beta-casein (beta-CN) showing properties of intrinsically unstructured proteins (IUP) displays many similarities with molecular chaperones and shows anti-aggregation activity in vitro. Chaperone activities of bovine and camel beta-CN were studied using alcohol dehydrogenase (ADH) as a substrate. To obtain an adequate relevant information about the chaperone capacities of studied caseins, three different physical parameters including chaperone constant (k(c), microM(-1)), thermal aggregation constant (k(T), degrees C(-1)) and aggregation rate constant (k(t), min(-1)) were measured. Bovine beta-CN displays greater chaperone activity than camel beta-CN. Fluorescence studies of 8-anilino-1-naphthalenesulfonic acid (ANS) binding demonstrated that bovine beta-CN is doted with larger effective hydrophobic surfaces at all studied temperatures than camel beta-CN. Greater relative hydrophobicity of bovine beta-CN than camel beta-CN may be a factor responsible for stronger interactions of bovine beta-CN with the aggregation-prone pre denatured molecular species of the substrate ADH, which resulted in greater chaperone activity of bovine beta-CN.

  5. The Serum Complement System: A Simplified Laboratory Exercise to Measure the Activity of an Important Component of the Immune System

    ERIC Educational Resources Information Center

    Inglis, Jordan E.; Radziwon, Kimberly A.; Maniero, Gregory D.

    2008-01-01

    The immune system is a vital physiological component that affords animals protection from disease and is composed of innate and adaptive mechanisms that rely on cellular and dissolved components. The serum complement system is a series of dissolved proteins that protect against a variety of pathogens. The activity of complement in serum can be…

  6. Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

    PubMed

    Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

    2016-02-01

    Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

  7. Enthalpy/entropy driven activation of the first interquinone electron transfer in bacterial photosynthetic reaction centers embedded in vesicles of physiologically important phospholipids.

    PubMed

    Milano, Francesco; Dorogi, Márta; Szebényi, Kornélia; Nagy, László; Maróti, Péter; Váró, György; Giotta, Livia; Agostiano, Angela; Trotta, Massimo

    2007-01-01

    The thermodynamics and kinetics of light-induced electron transfer in bacterial photosynthetic RCs are sensitive to physiologically important lipids (phosphatidylcholine, cardiolipin and phosphatidylglycerol) in the environment. The analysis of the temperature-dependence of the rate of the P(+)Q(A)(-)Q(B)-->P(+)Q(A)Q(B)(-) interquinone electron transfer revealed high enthalpy change of activation in zwitterionic or neutral micelles and vesicles and low enthalpy change of activation in vesicles constituted of negatively charged phospholipids. The entropy change of activation was compensated by the changes of enthalpy, thus the free energy change of activation ( approximately 500 meV) did not show large variation in vesicles of different lipids.

  8. ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M checkpoint activation.

    PubMed

    Kolb, Ryan H; Greer, Patrick M; Cao, Phu T; Cowan, Kenneth H; Yan, Ying

    2012-01-01

    Topo II poisons, which target topoisomerase II (topo II) to generate enzyme mediated DNA damage, have been commonly used for anti-cancer treatment. While clinical evidence demonstrate a capability of topo II poisons in inducing apoptosis in cancer cells, accumulating evidence also show that topo II poison treatment frequently results in cell cycle arrest in cancer cells, which was associated with subsequent resistance to these treatments. Results in this report indicate that treatment of MCF-7 and T47D breast cancer cells with topo II poisons resulted in an increased phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and an subsequent induction of G2/M cell cycle arrest. Furthermore, inhibition of ERK1/2 activation using specific inhibitors markedly attenuated the topo II poison-induced G2/M arrest and diminished the topo II poison-induced activation of ATR and Chk1 kinases. Moreover, decreased expression of ATR by specific shRNA diminished topo II poison-induced G2/M arrest but had no effect on topo II poison-induced ERK1/2 activation. In contrast, inhibition of ERK1/2 signaling had little, if any, effect on topo II poison-induced ATM activation. In addition, ATM inhibition by either incubation of cells with ATM specific inhibitor or transfection of cells with ATM specific siRNA did not block topo II poison-induced G2/M arrest. Ultimately, inhibition of ERK1/2 signaling greatly enhanced topo II poison-induced apoptosis. These results implicate a critical role for ERK1/2 signaling in the activation of G2/M checkpoint response following topo II poison treatment, which protects cells from topo II poison-induced apoptosis.

  9. 2-(Nitroaryl)benzothiazole and benzoxazole derivatives as fluorogenic substrates for the detection of nitroreductase activity in clinically important microorganisms.

    PubMed

    Cellier, Marie; Gignoux, Amandine; James, Arthur L; Orenga, Sylvain; Perry, John D; Robinson, Shaun N; Stanforth, Stephen P; Turnbull, Graeme

    2015-12-15

    A series of carboxy-substituted 2-(nitroaryl)benzothiazole derivatives and carboxy-substituted 2-(nitroaryl)benzoxazole derivatives were prepared and evaluated as potential nitroreductase substrates for the purpose of detecting clinically important microorganisms. Several of the substrates produced highly fluorescent colonies with the majority of a panel of 10 Gram-negative bacteria and also with two of a panel of 8 Gram-positive bacteria.

  10. Important role of surface fluoride in nitrogen-doped TiO2 nanoparticles with visible light photocatalytic activity.

    PubMed

    Brauer, Jonathan I; Szulczewski, Greg

    2014-12-11

    Nitrogen-doped TiO2 nanoparticles have been synthesized using sol-gel methods and subsequently fluorinated at room temperature by aging in acidic solutions of NaF. The nanoparticles were characterized by X-ray photoelectron spectroscopy, X-ray diffraction, UV-vis, and IR diffuse reflectance spectroscopy. After aging at room temperature in NaF solutions, the Ti-OH groups on the surface of the TiO2 nanoparticles were replaced by Ti-F bonds, which resulted in a decrease of the point of zero charge from pH 5.4 to 2.8. Most importantly, the nitrogen dopants were retained after the fluorination process, and the amorphous nanoparticles were partially converted into the anatase phase. Annealing the photocatalysts resulted in a decrease of both the nitrogen and fluoride atomic concentration. Diffuse reflectance spectra show an increase in absorbance above 400 nm after annealing the F,N-doped TiO2, which suggests the formation of color centers. The photoactivity of the F,N-doped and N-doped TiO2 catalysts were evaluated by monitoring by the decolorization of methylene blue with visible light. Mass spectrometric analysis revealed that methylene blue undergoes successive demethylation, and more importantly, the rate of decolorization depends on the fluoride concentration. These results show the importance of a two-step synthesis method to independently control the nitrogen and fluoride concentration.

  11. [Correlation between clinical parameters and quantitative analysis of inflammatory infiltrate. Importance in the diagnosis of active periodontal disease].

    PubMed

    Mendieta Fiter, C

    1989-05-01

    Recent studies have indicated that the destruction in chronic periodontal disease occurs in relatively short periods of time which are followed of prolonged periods of inactivity. These bursts of activity are characterized by an increase in the inflammatory reaction. It has been the purpose of this paper to study the correlation between the clinical measurements of periodontal disease and the histomorphometric quantification of areas of dense inflammatory infiltrate. The results of this study show that the clinical parameters that measure gingival inflammation or loss of periodontal attachment are useful to distinguish pathology from normal (p less than 0.003), but lack sensitivity to detect burst of periodontal disease activity (p greater than 0.05).

  12. A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid ‘‘Harmine’’

    PubMed Central

    Patel, K; Gadewar, M; Tripathi, R; Prasad, SK; Patel, Dinesh Kumar

    2012-01-01

    Harmine, a beta-carboline alkaloid, is widely distributed in the plants, marine creatures, insects, mammalians as well as in human tissues and body fluids. Harmine was originally isolated from seeds of Peganum harmal in 1847 having a core indole structure and a pyridine ring. Harmine has various types of pharmacological activities such as antimicrobial, antifungal, antitumor, cytotoxic, antiplasmodial, antioxidaant, antimutagenic, antigenotoxic and hallucinogenic properties. It acts on gamma-aminobutyric acid type A and monoamine oxidase A or B receptor, enhances insulin sensitivity and also produces vasorelaxant effect. Harmine prevents bone loss by suppressing osteoclastogenesis. The current review gives an overview on pharmacological activity and analytical techniques of harmine, which may be useful for researcheres to explore the hidden potential of harmine and and will also help in developing new drugs for the treatment of various diseases. PMID:23569990

  13. Importance of clustered 2'-O-(2-aminoethyl) residues for the gene targeting activity of triple helix-forming oligonucleotides.

    PubMed

    Puri, Nitin; Majumdar, Alokes; Cuenoud, Bernard; Miller, Paul S; Seidman, Michael M

    2004-02-10

    We are developing triple helix-forming oligonucleotides (TFOs) as gene targeting reagents in living mammalian cells. We have described psoralen-linked TFOs with 2'-O-methyl and 2'-O-(2-aminoethyl) (2'-AE) substitutions that are active in a gene knockout assay in cultured cells. The assay is based on mutagenesis by psoralen, a photoactive DNA cross-linker. Previous work showed that TFOs with three or four 2'-AE residues were disproportionately more active than those with one or two substitutions. Here we demonstrate that for optimal bioactivity the 2'-AE residues must be clustered rather than dispersed. We have further characterized bioactive and inactive TFOs in an effort to identify biochemical and biophysical correlates of biological activity. While thermal stability is a standard monitor of TFO biophysical activity, we find that T(m) values do not distinguish bioactive and inactive TFOs. In contrast, measurements of TFO association rates appear to correlate well with bioactivity, in that triplex formation occurs disproportionately faster with the TFOs containing three or four 2'-AE residues. We asked if extending the incubation time prior to photoactivation would enhance the bioactivity of a TFO with a slow on rate relative to the TFO with a faster association rate. However, there was no change in bioactivity differential. These results are compatible with a model in which TFO binding in vivo is followed by relatively rapid elution by cellular functions, similar to that described for transcription factors. Under these circumstances, TFOs with faster on rates would be favored because they would be more likely to be in triplexes at the time of photoactivation.

  14. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

    PubMed

    Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

    2012-01-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

  15. The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing.

    PubMed

    Theilgaard-Mönch, Kim; Knudsen, Steen; Follin, Per; Borregaard, Niels

    2004-06-15

    To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing.

  16. Iron, lactoferrin and iron regulatory protein activity in the synovium; relative importance of iron loading and the inflammatory response

    PubMed Central

    Guillen, C; McInnes, I; Kruger, H; Brock, J

    1998-01-01

    OBJECTIVES—To determine the ability of lactoferrin in rheumatoid arthritis (RA) synovial fluid to bind "free" iron, and to study the regulatory mechanisms therein that control iron homeostasis.
METHODS—"Free" iron was determined by the bleomycin assay and lactoferrin concentrations by enzyme linked immunosorbent assay. The activities of iron regulatory protein (IRP) and NF-κB in synovial fluid cells were assayed by mobility shift assay.
RESULTS—30% of synovial fluids contained "free" iron and in these, lactoferrin concentrations were significantly lower than in those with no "free" iron (p<0.01). Addition of exogenous lactoferrin consistently reduced the amount of "free" iron in positive synovial fluids. IRP activity in synovial cells did not correlate with synovial fluid iron concentrations but did correlate with NF-κB activation and with serum C reactive protein.
CONCLUSION—Lactoferrin may prevent iron mediated tissue damage in RA by reducing "free" synovial iron concentration when inflammatory stimuli have disregulated IRP mediated iron homeostasis.

 Keywords: lactoferrin; rheumatoid arthritis; inflammation PMID:9741316

  17. Importance of surface carbide formation on the activity and selectivity of Pd surfaces in the selective hydrogenation of acetylene

    NASA Astrophysics Data System (ADS)

    Yang, Bo; Burch, Robbie; Hardacre, Christopher; Hu, P.; Hughes, Philip

    2016-04-01

    A recent experimental investigation (Kim et al. J. Catal. 306 (2013) 146-154) on the selective hydrogenation of acetylene over Pd nanoparticles with different shapes concluded that Pd(100) showed higher activity and selectivity than Pd(111) for acetylene hydrogenation. However, our recent density functional calculations (Yang et al. J. Catal. 305 (2013) 264-276) observed that the clean Pd(111) surface should result in higher activity and ethylene selectivity compared with the clean Pd(100) surface for acetylene hydrogenation. In the current work, using density functional theory calculations, we find that Pd(100) in the carbide form gives rise to higher activity and selectivity than Pd(111) carbide. These results indicate that the catalyst surface is most likely in the carbide form under the experimental reaction conditions. Furthermore, the adsorption energies of hydrogen atoms as a function of the hydrogen coverage at the surface and subsurface sites over Pd(100) are compared with those over Pd(111), and it is found that the adsorption of hydrogen atoms is always less favoured on Pd(100) over the whole coverage range. This suggests that the Pd(100) hydride surface will be less stable than the Pd(111) hydride surface, which is also in accordance with the experimental results reported.

  18. Understanding the Importance of Context: A Qualitative Study of a Location-Based Exergame to Enhance School Childrens Physical Activity

    PubMed Central

    Jepson, Ruth; Macvean, Andrew; Gray, Stuart

    2016-01-01

    Many public health interventions are less effective than expected in ‘real life settings’, yet little work is undertaken to understand the reasons why. The effectiveness of complex public health interventions can often be traced back to a robust programme theory (how and why an intervention brings about a change in outcome(s)) and assumptions that are made about the context in which it is implemented. Understanding whether effectiveness (or lack thereof) is due to the intervention or the context is hugely helpful in decisions about whether to a) modify the intervention; b) modify the context; c) stop providing the intervention. Exergames–also known as Active Video Games or AVGS–are video games which use the player's bodily movements as input and have potential to increase physical activity in children. However, the results of a recent pilot randomised controlled trial (RCT) of a location-based exergame (FitQuest) in a school setting were inconclusive; no significant effect was detected for any of the outcome measures. The aim of this study was to explore whether the programme theory for FitQuest was correct with respect to how and why it would change children’s perceptions of physical activity (PA) and exercise self-efficacy in the school setting. A further aim was to investigate the features of the school setting (context) that may impact on FitQuest’s implementation and effectiveness. Qualitative data (gathered during the RCT) were gathered from interviews with teachers and children, and observation of sessions using FitQuest. Thematic analysis indicated that whilst children enjoyed playing the game, engaged with goal setting within the game context and undertook low to vigorous physical activity, there were significant contextual factors that prevented it from being played as often as intended. These included environmental factors (e.g. size of the playground), school factors (cancellations due to other activities), school technology policy (rules

  19. 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.

  20. Sports Facilities, Shopping Centers or Homes: What Locations are Important for Adults' Physical Activity? A Cross-Sectional Study.

    PubMed

    Jansen, Marijke; Ettema, Dick; Pierik, Frank; Dijst, Martin

    2016-03-04

    Physical activity (PA) is influenced by the built environment. However, little is known about the types of built environment where adults spend their time, and at what levels of PA they engage in those environments. Understanding the effect of the built environment on PA requires insight into PA behavior at different types of locations (e.g., home, work, shopping centers, and sports facilities). Therefore, this study describes where adults aged 45-65 years were active with moderate-to-vigorous intensity (MVPA), and examines associations of socio-demographic factors and neighborhood with MVPA at these locations. Participants' (N = 308) PA was measured for seven days using accelerometers and GPS-devices. Adults spent most minutes of MVPA at home and work. Highest MVPA-ratios of total time spent at a location were achieved in sports facilities and during transport. Neighborhood characteristics and socio-demographic factors such as work status, health status and household structure, had significant effects on MVPA at various locations and on total MVPA. Understanding PA behavior at various locations may provide insights that allow professionals in different domains (e.g., health, landscaping, urban planning) to develop strategies to stimulate PA.

  1. Sports Facilities, Shopping Centers or Homes: What Locations are Important for Adults’ Physical Activity? A Cross-Sectional Study

    PubMed Central

    Jansen, Marijke; Ettema, Dick; Pierik, Frank; Dijst, Martin

    2016-01-01

    Physical activity (PA) is influenced by the built environment. However, little is known about the types of built environment where adults spend their time, and at what levels of PA they engage in those environments. Understanding the effect of the built environment on PA requires insight into PA behavior at different types of locations (e.g., home, work, shopping centers, and sports facilities). Therefore, this study describes where adults aged 45–65 years were active with moderate-to-vigorous intensity (MVPA), and examines associations of socio-demographic factors and neighborhood with MVPA at these locations. Participants’ (N = 308) PA was measured for seven days using accelerometers and GPS-devices. Adults spent most minutes of MVPA at home and work. Highest MVPA-ratios of total time spent at a location were achieved in sports facilities and during transport. Neighborhood characteristics and socio-demographic factors such as work status, health status and household structure, had significant effects on MVPA at various locations and on total MVPA. Understanding PA behavior at various locations may provide insights that allow professionals in different domains (e.g., health, landscaping, urban planning) to develop strategies to stimulate PA. PMID:26959041

  2. 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

  3. The importance of the activation volume for the description of the molecular dynamics of glass-forming liquids

    NASA Astrophysics Data System (ADS)

    Kaminski, K.; Pawlus, S.; Adrjanowicz, K.; Wojnarowska, Z.; Wlodarczyk, P.; Paluch, M.

    2012-02-01

    High pressure dielectric measurements were carried out on hydrogen bonded d-glucose and two van der Waals peracetyl saccharides, i.e. α pentaacetyl glucose and α octaacetyl maltose. In this study we found that after removing H bonds, the molecular dynamics of both modified saccharides is very sensitive to pressure, as reflected by a large value of the pressure coefficient of the glass transition temperature, equal to 270 K GPa-1 and 280 K GPa-1 for α pentaacetyl glucose and α octaacetyl maltose, respectively. On the other hand, dTg/dP for d-glucose is much lower, equal to 67 K GPa-1. Our result confirms the general rule that the hydrogen bonding glass-forming liquids exhibit much lower values of dTg/dP compared to the van der Waals systems. Additionally, on the basis of results reported herein and also recent literature data for polyalcohols, we point out that the activation volume correlates fairly well with the molecular volume in the case of hydrogen bonding liquids. On the other hand, much larger values of the activation volumes at Tg with respect to the molecular volumes were found for both peracetyl saccharides.

  4. Predictors of Unprotected Sex among Young Sexually Active African American, Hispanic, and White MSM: The Importance of Ethnicity and Culture

    PubMed Central

    Fernández, M. Isabel; Harper, Gary W.; Hidalgo, Marco A.; Jamil, Omar B.; Torres, Rodrigo Sebastián

    2010-01-01

    Despite the recognized need for culturally tailored HIV prevention interventions for gay, bisexual, and questioning youth, few studies have examined if predictors of unprotected sex vary for youth from different ethnic groups. This study reports on a sample of 189 gay, bisexual, and questioning youth (age 15–22) from three racial/ethnic backgrounds (African American, Hispanic, and White) recruited in Chicago, IL and Miami-Dade and Broward Counties, Florida. For African American youth, being in a long-term relationship, having been kicked out of the home for having sex with men, and younger age at initiation of sexual behavior were associated with unprotected sex. For Hispanic youth, higher ethnic identification and older age at initiation of sexual behavior were associated with unprotected sex. For White youth, no predictors were associated with unprotected sex. Our findings point to the importance of understanding the varying predictors of unprotected sex and integrating them into tailored prevention interventions. PMID:17721725

  5. Predictors of unprotected sex among young sexually active African American, Hispanic, and White MSM: the importance of ethnicity and culture.

    PubMed

    Warren, Jacob C; Fernández, M Isabel; Harper, Gary W; Hidalgo, Marco A; Jamil, Omar B; Torres, Rodrigo Sebastián

    2008-05-01

    Despite the recognized need for culturally tailored HIV prevention interventions for gay, bisexual, and questioning youth, few studies have examined if predictors of unprotected sex vary for youth from different ethnic groups. This study reports on a sample of 189 gay, bisexual, and questioning youth (age 15-22) from three racial/ethnic backgrounds (African American, Hispanic, and White) recruited in Chicago, IL and Miami-Dade and Broward Counties, Florida. For African American youth, being in a long-term relationship, having been kicked out of the home for having sex with men, and younger age at initiation of sexual behavior were associated with unprotected sex. For Hispanic youth, higher ethnic identification and older age at initiation of sexual behavior were associated with unprotected sex. For White youth, no predictors were associated with unprotected sex. Our findings point to the importance of understanding the varying predictors of unprotected sex and integrating them into tailored prevention interventions.

  6. A trustful relationship—the importance for relatives to actively participate in the meeting with the physician

    PubMed Central

    2013-01-01

    In previous research, no uniform picture emerged of the role of relatives in the meeting between an elderly patient and a physician. Knowledge about relatives’ experiences of the meeting between an elderly patient and a physician will help healthcare practitioners better understand the role of relatives during the meeting and how practitioners can assist relatives in assuming their supporting role more efficiently. The purpose of this study is to explore experiences of relatives of meeting with the physician in a hospital setting when an elderly patient is discharged from hospital care to home care, in order to identify aspects that may facilitate relatives in taking up their role in a more efficient manner. This descriptive and exploratory study is based on 20 interviews with relatives. The result shows that the physician's communication style influences the meeting between the relative, the elderly patient, and the physician, and that this style is the result of power and interaction. A trustful relationship during the meeting between the relative and the physician can increase the relative's feeling of confidence with the healthcare organization and treatment of the elderly patient. The relative has an important supporting role in the care for the elderly family member, both in the hospital and the home setting. It is likely that the relative's value as a resource, for both the patient and the physician, increases as the relative experiences feelings of confidence in the meeting with the physician. It is therefore of value to increase our knowledge about the conditions and circumstances facilitating and/or hampering the meeting between the relative and the physician. The result stresses the importance of encouraging relatives to participate in the meeting. Physicians need more guidance and training in communication skills, respectful demeanor, and collaboration while meeting the relatives. PMID:23694680

  7. Growth response of Douglas-fir seedlings to nitrogen fertilization: importance of Rubisco activation state and respiration rates.

    PubMed

    Manter, Daniel K; Kavanagh, Kathleen L; Rose, Cathy L

    2005-08-01

    High foliar nitrogen concentration ([N]) is associated with high rates of photosynthesis and thus high tree productivity; however, at excessive [N], tree productivity is reduced. Reports of excessive [N] in the Douglas-fir forests of the Oregon Coast Range prompted this investigation of growth and needle physiological responses to increasing foliar N concentrations in 1-year-old Douglas-fir seedlings. After 1 year of N fertilization, total seedling biomass increased with each successive increase in N fertilizer concentration, except in the highest N fertilization treatment. Of the many physiological responses that were analyzed, only photosynthetic capacity (i.e., Vcmax), respiration rates and leaf specific conductance (KL) differed significantly between N treatments. Photosynthetic capacity showed a curvilinear relationship with foliar [N], reaching an apparent maximum rate when needle N concentrations exceeded about 12 mg g(-1). In vitro measurements of ribulose-1,5-bisphosphate carboxylase (Rubisco) activity suggested that photosynthetic capacity was best related to activated, not total, Rubisco content. Rubisco activation state declined as foliar [N] increased, and based on its significant correlation (r2= 0.63) with foliar Mn:Mg ratios, it may be related to Mn inactivation of Rubisco. Respiration rates increased linearly as foliar N concentration increased (r2= 0.84). The value of K(L) also increased as foliar [N] increased, reaching a maximum when foliar [N] exceeded about 10 mg g(-1). Changes in K(L) were unrelated to changes in leaf area or sapwood area because leaf area to sapwood area ratios remained constant. Cumulative effects of the observed physiological responses to N fertilization were analyzed by modeling annual net CO2 assimilation (Anet) based on treatment specific values of Vcmax, dark respiration (Rdark) and KL. Estimates of Anet were highly correlated with measured total seedling biomass (r2= 0.992), suggesting that long-term, cumulative

  8. Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation.

    PubMed

    Peeters, M C; van Westen, G J P; Li, Q; IJzerman, A P

    2011-01-01

    G protein-coupled receptors (GPCRs) are the major drug target of medicines on the market today. Therefore, much research is and has been devoted to the elucidation of the function and three-dimensional structure of this large family of membrane proteins, which includes multiple conserved transmembrane domains connected by intra- and extracellular loops. In the last few years, the less conserved extracellular loops have garnered increasing interest, particularly after the publication of several GPCR crystal structures that clearly show the extracellular loops to be involved in ligand binding. This review will summarize the recent progress made in the clarification of the ligand binding and activation mechanism of class-A GPCRs and the role of extracellular loops in this process.

  9. Structure-activity predictions of properties of organophosphorus pesticides and chemical agents important for optical detection. Master`s thesis

    SciTech Connect

    Porte, R.E.

    1995-12-01

    This thesis presents the results of an investigation for estimating various physicochemical properties of chemical warfare agents and organophosphorus pesticides. The determination of aqueous solubility, - octanol/water partition coefficients, and alkaline hydrolysis rate constants will be used in the development of a chemical sensor using fiber optic spectroscopy. These three parameters will effect the limit of detection for each compound by limiting the concentration in the detector. The parameters were estimated by linear free energy relationships and quantitative structure activity relationships using experimental data for compounds of similar chemical structure. The results of this thesis showed that the hydrophobic medium represented by 1-octanol did concentrate the OP pesticides but did not significantly concentrate CWA, CWA simulants, or CWA hydrolysis products. Correlations were evaluated for six classes of organophosphorus compounds. The limitation of this approach to predicting physicochemical parameters is not in the molecular descriptors used in the regression equations but in the availability of existing experimental data.

  10. Weight loss and physical activity for disease prevention in obese older adults: an important role for lifestyle management.

    PubMed

    Valencia, Willy Marcos; Stoutenberg, Mark; Florez, Hermes

    2014-10-01

    Weight loss in older adults has been a controversial topic for more than a decade. An obesity paradox has been previously described and the issue of weight status on health outcomes remains a highly debated topic. However, there is little doubt that physical activity (PA) has a myriad of benefits in older adults, especially in obese individuals who are inactive and have a poor cardiometabolic profile. In this review, we offer a critical view to clarify misunderstandings regarding the obesity paradox, particularly as it relates to obese older adults. We also review the evidence on PA and lifestyle interventions for the improvement of cardiorespiratory fitness, which can prevent disease and provide benefits to obese older adults, independent of weight changes.

  11. Increasing the catalytic activity of Bilirubin oxidase from Bacillus pumilus: Importance of host strain and chaperones proteins.

    PubMed

    Gounel, Sébastien; Rouhana, Jad; Stines-Chaumeil, Claire; Cadet, Marine; Mano, Nicolas

    2016-07-20

    Aggregation of recombinant proteins into inclusion bodies (IBs) is the main problem of the expression of multicopper oxidase in Escherichia coli. It is usually attributed to inefficient folding of proteins due to the lack of copper and/or unavailability of chaperone proteins. The general strategies reported to overcome this issue have been focused on increasing the intracellular copper concentration. Here we report a complementary method to optimize the expression in E. coli of a promising Bilirubin oxidase (BOD) isolated from Bacillus pumilus. First, as this BOD has a disulfide bridge, we switched E.coli strain from BL21 (DE3) to Origami B (DE3), known to promote the formation of disulfide bridges in the bacterial cytoplasm. In a second step, we investigate the effect of co-expression of chaperone proteins on the protein production and specific activity. Our strategy allowed increasing the final amount of enzyme by 858% and its catalytic rate constant by 83%.

  12. Monitoring weekly heart rate variability in futsal players during the preseason: the importance of maintaining high vagal activity.

    PubMed

    Nakamura, Fabio Y; Pereira, Lucas A; Rabelo, Felipe N; Flatt, Andrew A; Esco, Michael R; Bertollo, Maurizio; Loturco, Irineu

    2016-12-01

    This study aimed to compare the weekly natural log of the root-mean-square difference of successive normal inter-beat (RR) intervals (ln RMSSDWeekly) and its coefficient of variation (ln RMSSDCV) in response to 5 weeks of preseason training in professional male futsal players. A secondary aim was to assess the relationship between ln RMSSDWeekly and ln RMSSDCV. The ln RMSSD is a measure of cardiac-vagal activity, and ln RMSSDCV represents the perturbations of cardiac autonomic homeostasis, which may be useful for assessing how athletes are coping with training. Ten futsal players had their resting ln RMSSD recorded prior to the first daily training session on four out of approximately five regular training days · week(-1). Session rating of perceived exertion (sRPE) was quantified for all training sessions. Despite weekly sRPE varying between 3455 ± 300 and 5243 ± 463 arbitrary units (a.u.), the group changes in ln RMSSDWeekly were rated as unclear (using magnitude-based inference), although large inter-individual variability in ln RMSSD responses was observed. The ln RMSSDCV in weeks 4 and 5 were likely lower than the previous weeks. A large and significant negative correlation (r = -0.53; CI 90%: -0.36; -0.67) was found between ln RMSSD and ln RMSSDCV. Therefore, monitoring individual ln RMSSD responses is suggested since large inter-individual variations may exist in response to futsal training. In addition, higher values of ln RMSSD are associated with lower oscillations of cardiac autonomic activity.

  13. Prediction of prognosis of ALS: Importance of active denervation findings of the cervical-upper limb area and trunk area.

    PubMed

    Sato, Yoko; Nakatani, Eiji; Watanabe, Yasuhiro; Fukushima, Masanori; Nakashima, Kenji; Kannagi, Mari; Kanatani, Yasuhiro; Mizushima, Hiroshi

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by serious muscle atrophy and weakness. The purpose of this study was to find prognostic factors in patients with mild ALS using application forms for the Specified Disease Treatment Research Program in Japan. We classified ALS as mild, moderate and severe. The subjects consisted of 363 patients with mild ALS who underwent needle electromyography at registration and were followed for more than one year. Time to progression to severe ALS and time to deterioration of activities of daily living such as speech dysfunction, upper limb dysfunction, and walking disability were used as outcomes. Cox proportional hazards model analysis was performed to identify prognostic factors. Of the patients with initially mild ALS, 38.3% (139/363) had progressed severe ALS at the last follow-up. In multivariate analysis of time to progression to severe ALS, bulbar onset (hazard ratio [95% confidence interval]: 1.68 [1.13-2.49], p = 0.010), tongue atrophy (1.69 [1.14-2.51], p = 0.009), dyspnea (1.57 [1.02-2.41], p = 0.042) and active denervation findings (ADFs) of the cervical-upper limb area (1.81 [1.25-2.63], p = 0.002) emerged as prognostic factors. Furthermore ADFs in the trunk area were prognostic factors for upper limb dysfunction and walking disability (1.72 [1.05-2.81], p = 0.031, and 1.97 [1.09-3.59], p = 0.026). In conclusion ADFs of the cervical-upper limb area and trunk area were prognostic factors in ALS patients.

  14. Prediction of prognosis of ALS: Importance of active denervation findings of the cervical-upper limb area and trunk area

    PubMed Central

    Sato, Yoko; Nakatani, Eiji; Watanabe, Yasuhiro; Fukushima, Masanori; Nakashima, Kenji; Kannagi, Mari; Kanatani, Yasuhiro; Mizushima, Hiroshi

    2015-01-01

    Summary Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by serious muscle atrophy and weakness. The purpose of this study was to find prognostic factors in patients with mild ALS using application forms for the Specified Disease Treatment Research Program in Japan. We classified ALS as mild, moderate and severe. The subjects consisted of 363 patients with mild ALS who underwent needle electromyography at registration and were followed for more than one year. Time to progression to severe ALS and time to deterioration of activities of daily living such as speech dysfunction, upper limb dysfunction, and walking disability were used as outcomes. Cox proportional hazards model analysis was performed to identify prognostic factors. Of the patients with initially mild ALS, 38.3% (139/363) had progressed severe ALS at the last follow-up. In multivariate analysis of time to progression to severe ALS, bulbar onset (hazard ratio [95% confidence interval]: 1.68 [1.13–2.49], p = 0.010), tongue atrophy (1.69 [1.14–2.51], p = 0.009), dyspnea (1.57 [1.02–2.41], p = 0.042) and active denervation findings (ADFs) of the cervical-upper limb area (1.81 [1.25–2.63], p = 0.002) emerged as prognostic factors. Furthermore ADFs in the trunk area were prognostic factors for upper limb dysfunction and walking disability (1.72 [1.05–2.81], p = 0.031, and 1.97 [1.09–3.59], p = 0.026). In conclusion ADFs of the cervical-upper limb area and trunk area were prognostic factors in ALS patients. PMID:26668778

  15. An intermediate-conductance Ca2+-activated K+ channel is important for secretion in pancreatic duct cells.

    PubMed

    Hayashi, Mikio; Wang, Jing; Hede, Susanne E; Novak, Ivana

    2012-07-15

    Potassium channels play a vital role in maintaining the membrane potential and the driving force for anion secretion in epithelia. In pancreatic ducts, which secrete bicarbonate-rich fluid, the identity of K(+) channels has not been extensively investigated. In this study, we investigated the molecular basis of functional K(+) channels in rodent and human pancreatic ducts (Capan-1, PANC-1, and CFPAC-1) using molecular and electrophysiological techniques. RT-PCR analysis revealed mRNAs for KCNQ1, KCNH2, KCNH5, KCNT1, and KCNT2, as well as KCNN4 coding for the following channels: KVLQT1; HERG; EAG2; Slack; Slick; and an intermediate-conductance Ca(2+)-activated K(+) (IK) channel (K(Ca)3.1). The following functional studies were focused on the IK channel. 5,6-Dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DC-EBIO), an activator of IK channel, increased equivalent short-circuit current (I(sc)) in Capan-1 monolayer, consistent with a secretory response. Clotrimazole, a blocker of IK channel, inhibited I(sc). IK channel blockers depolarized the membrane potential of cells in microperfused ducts dissected from rodent pancreas. Cell-attached patch-clamp single-channel recordings revealed IK channels with an average conductance of 80 pS in freshly isolated rodent duct cells. These results indicated that the IK channels may, at least in part, be involved in setting the resting membrane potential. Furthermore, the IK channels are involved in anion and potassium transport in stimulated pancreatic ducts.

  16. Ixodes (Ixodes) scapularis (Acari:Ixodidae): redescription of all active stages, distribution, hosts, geographical variation, and medical and veterinary importance.

    PubMed

    Keirans, J E; Hutcheson, H J; Durden, L A; Klompen, J S

    1996-05-01

    The blacklegged tick, Ixodes (Ixodes) scapularis Say, 1821, is redescribed, based on laboratory reared specimens originating in Bulloch County, Georgia. Information on distribution, host associations, morphological variation, and medical/veterinary importance is also presented. A great deal of recent work has focused on this species because it is the principal vector of the agent of Lyme disease (Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwaldt & Brenner) in eastern North America. Its distribution appears to be expanding, and includes the state of Florida in the southeastern United States north to the provinces of Nova Scotia and Prince Edward Island, Canada, west to North and South Dakota, United States, and south to the state of Coahuila, Mexico. Although I. scapularis feeds on at least 125 species of North American vertebrates (54 mammalian, 57 avian, and 14 lizard species), analysis of the U.S. National Tick Collection holdings show that white-tailed deer, Odocoileus virginianus (Zimmermann), cattle, Bos taurus L., dogs, Canis lupus L., and other medium-to-large sized mammals are important hosts for adults as are native mice and other small mammals, certain ground-frequenting birds, skinks, and glass lizards for nymphs and larvae. This tick is a polytypic species exhibiting north-south and east-west morphological clines. Analysis of variance and Student-Newman-Keuls multiple comparisons revealed significant interpopulational variation that is expressed most significantly in the nymphal stage. Nymphs from northern (Minnesota, Massachusetts, Maryland) populations had relatively larger basis capituli with shorter cornua (except Maryland) than southern (North Carolina, Georgia) populations. Midwestern populations (Minnesota, Missouri) differed from eastern populations (Massachusetts, Maryland, North Carolina, Georgia) in idiosomal characters (broader scuta, larger coxae III, and IV). In addition to Lyme disease, this tick is also a primary vector of the

  17. Histidine and Aspartic Acid Residues Important for Immunoglobulin G Endopeptidase Activity of the Group A Streptococcus Opsonophagocytosis-Inhibiting Mac Protein

    PubMed Central

    Lei, Benfang; Liu, Mengyao; Meyers, Elishia G.; Manning, Heather M.; Nagiec, Michael J.; Musser, James M.

    2003-01-01

    The secreted Mac protein made by serotype M1 group A Streptococcus (GAS) (designated Mac5005) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils. This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG). Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity. Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity. Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level. The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein. These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac. PMID:12704162

  18. OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis.

    PubMed

    Xia, Xiaoyun; Larios-Valencia, Jessie; Liu, Zhi; Xiang, Fu; Kan, Biao; Wang, Hui; Zhu, Jun

    2017-01-01

    Vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. This Gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). In order to further the understanding of V. cholerae's transcriptional response to ROS, we performed an RNA sequencing analysis to determine the transcriptional profile of V. cholerae when exposed to hydrogen hydroperoxide. Of 135 differentially expressed genes, VC0139 was amongst the genes with the largest induction. VC0139 encodes a protein homologous to the DPS (DNA-binding protein from starved cells) protein family, which are widely conserved and are implicated in ROS resistance in other bacteria. Using a promoter reporter assay, we show that during exponential growth, dps is induced by H2O2 in a manner dependent on the ROS-sensing transcriptional regulator, OxyR. Upon entry into stationary phase, the major stationary phase regulator RpoS is required to transcribe dps. Deletion of dps impaired V. cholerae resistance to both inorganic and organic hydroperoxides. Furthermore, we show that Dps is involved in resistance to multiple environmental stresses. Finally, we found that Dps is important for V. cholerae adult mouse colonization, but becomes dispensable in the presence of antioxidants. Taken together, our results suggest that Dps plays vital roles in both V. cholerae stress resistance and pathogenesis.

  19. OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis

    PubMed Central

    Xia, Xiaoyun; Larios-Valencia, Jessie; Liu, Zhi; Xiang, Fu; Kan, Biao; Zhu, Jun

    2017-01-01

    Vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. This Gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). In order to further the understanding of V. cholerae’s transcriptional response to ROS, we performed an RNA sequencing analysis to determine the transcriptional profile of V. cholerae when exposed to hydrogen hydroperoxide. Of 135 differentially expressed genes, VC0139 was amongst the genes with the largest induction. VC0139 encodes a protein homologous to the DPS (DNA-binding protein from starved cells) protein family, which are widely conserved and are implicated in ROS resistance in other bacteria. Using a promoter reporter assay, we show that during exponential growth, dps is induced by H2O2 in a manner dependent on the ROS-sensing transcriptional regulator, OxyR. Upon entry into stationary phase, the major stationary phase regulator RpoS is required to transcribe dps. Deletion of dps impaired V. cholerae resistance to both inorganic and organic hydroperoxides. Furthermore, we show that Dps is involved in resistance to multiple environmental stresses. Finally, we found that Dps is important for V. cholerae adult mouse colonization, but becomes dispensable in the presence of antioxidants. Taken together, our results suggest that Dps plays vital roles in both V. cholerae stress resistance and pathogenesis. PMID:28151956

  20. Fatty Amines from Little Black Ants, Monomorium minimum, and Their Biological Activities Against Red Imported Fire Ants, Solenopsis invicta.

    PubMed

    Wang, Lei; Chen, Jian

    2015-08-01

    Red imported fire ants, Solenopsis invicta, are significant invasive pests. Certain native ant species can compete with S. invicta, such as the little black ant, Monomorium minimum. Defensive secretions may contribute to the competition capacity of native ants. The chemistry of ant defensive secretions in the genus Monomorium has been subjected to extensive research. The insecticidal alkaloids, 2,5-dialkyl-pyrrolidines and 2,5-dialkyl-pyrrolines have been reported to dominate the venom of M. minimum. In this study, analysis of defensive secretions of workers and queens of M. minimum revealed two primary amines, decylamine and dodecylamine. Neither amine has been reported previously from natural sources. Toxicity and digging suppression by these two amines against S. invicta were examined. Decylamine had higher toxicity to S. invicta workers than dodecylamine, a quicker knockdown effect, and suppressed the digging behavior of S. invicta workers at lower concentration. However, the amount of fatty amines in an individual ant was not enough to knockdown a fire ant or suppress its digging behavior. These amines most likely work in concert with other components in the chemical defense of M. minimum.

  1. Identification of functionally important residues in the silkmoth pheromone biosynthesis-activating neuropeptide receptor, an insect ortholog of the vertebrate Neuromedin U Receptor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biosynthesis of sex pheromone components in many lepidopteran insects is regulated by interactions between pheromone biosynthesis-activating neuropeptide (PBAN) and the PBAN receptor (PBANR), a class-A G-protein-coupled receptor (GPCR). To identify functionally important amino acid residues in t...

  2. Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics.

    PubMed

    Adomako-Bonsu, Amma G; Chan, Sue Lf; Pratten, Margaret; Fry, Jeffrey R

    2017-04-01

    Persistent accumulation of reactive oxygen species causes cellular oxidative stress which contributes strongly towards the induction and progression of various diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. In the current study, rosmarinic acid (RA) and its key metabolites were evaluated in non-cellular and cellular antioxidant assays, using quercetin (Q) as a positive control. The non-cellular assay was performed as scavenging of DPPH radical, whilst the cellular assay was performed as protection from an oxidant stress. Radical-scavenging activity of RA and two of its primary metabolites, CA and DHPLA, were comparable to that of Q, whilst FA was of lower potency and m-CoA was inactive. In the cellular assay, RA and CA were markedly less potent than Q, with DHPLA, FA and m-CoA being inactive, this being true in short-term (5-h) or long-term (20-h) exposure conditions. However, antioxidant potency of Q and methyl rosmarinate, a non-ionisable ester of RA, was similar in the non-cellular and short-term cellular assays. It is proposed that marked ionisation of organic acids such as RA and its metabolites at physiological pH greatly limits their intracellular accumulation, and so attenuates intrinsic antioxidant ability demonstrated in the non-cellular assay. This study demonstrates some of the factors that prevent well-known phytochemicals from progressing further along the drug discovery chain.

  3. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.

    PubMed

    Myers, Jonathan; McAuley, Paul; Lavie, Carl J; Despres, Jean-Pierre; Arena, Ross; Kokkinos, Peter

    2015-01-01

    The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity.

  4. Physicochemical profiling of new aminopropan-2-ol derivatives with beta-adrenolytic activity: the importance for pharmacokinetic properties.

    PubMed

    Walczak, M Z

    2013-11-01

    A convenient procedure has been developed for the determination of dissociation constants (pKa) and partition (log P) and distribution (log D) coefficients of three new aminopropan-2-ol derivatives with beta-adrenolytic activity briefly called 2F109, ANBL and TWo8. The apparent acid dissociation constant (psKa) in these water-insoluble compounds was determined potentiometrically in dimethylformamide-water, dimethyl sulfoxide-water and methanol-water mixtures at a temperature of 25 degrees C. The aqueous pKa values assessed by Yasuda-Shedlovsky extrapolation were 8.64 +/- 0.06, 8.85 +/- 0.51 and 8.26 +/- 0.45 for 2F109, ANBL and TWo8, respectively. Lipophilicity expressed by chromatographic retention factor was determined by reversed phase liquid chromatography at pH 10.5 using a Zorbax Extend C18 column (log k10.5), and at pH 7.4 using an immobilized artificial membrane IAM.PC.DD2 column (log k7.4), respectively. The log k of each compound extrapolated to 100% aqueous phase (log kw10.5 and and log kw7.4) were corrected with log P and log D of acebutolol, atenolol, metoprolol,pindolol, propranolol and sotalol used as the model drugs.

  5. Importance of active tectonics during karst formation. A Middle Eocene to Pleistocene example of the Lina Moutains (Irian Jaya, Indonesia)

    NASA Astrophysics Data System (ADS)

    Thery, J.-M.; Pubellier, M.; Thery, B.; Butterlin, J.; Blondeau, A.; Adams, C. G.

    1999-05-01

    The Lina Moutains show a typical example of karst formation associated to recent and active tectonics. The limestone samples were collected from giant potholes present beneath the heavy rainforest, during speleological expeditions to the Bird's Head of Irian-Jaya. Micropalaeontological data allow us to give a Middle Pleistocene age for the most recent karst formation. A detailed stratigraphy between the Upper Lutetian and the Middle Pleistocene was recorded, with tectonic events during the Oligocene and Pleistocene. The edge of the resurgence layer was also dated. We also conclude the probable existence of a subterraneous network downhill of the karst within the most recent levels of the Kais Limestone formation. We replace this formation within the tectonic evolution of this area between the Eocene and the Middle Pleistocene, in conjunction with the oblique convergence of the Pacific plate carrying volcanic arc fragments and the Australian margin, which resulted in folding, normal faulting associated with local extension, and wrench motion, which are settings capable of creating uplift of the carbonated platform.

  6. Hfq-bridged ternary complex is important for translation activation of rpoS by DsrA

    PubMed Central

    Wang, Weiwei; Wang, Lijun; Wu, Jihui; Gong, Qingguo; Shi, Yunyu

    2013-01-01

    The rpoS mRNA, which encodes the master regulator σS of general stress response, requires Hfq-facilitated base pairing with DsrA small RNA for efficient translation at low temperatures. It has recently been proposed that one mechanism underlying Hfq action is to bridge a transient ternary complex by simultaneously binding to rpoS and DsrA. However, no structural evidence of Hfq simultaneously bound to different RNAs has been reported. We detected simultaneous binding of Hfq to rpoS and DsrA fragments. Crystal structures of AU6A•Hfq•A7 and Hfq•A7 complexes were resolved using 1.8- and 1.9-Å resolution, respectively. Ternary complex has been further verified in solution by NMR. In vivo, activation of rpoS translation requires intact Hfq, which is capable of bridging rpoS and DsrA simultaneously into ternary complex. This ternary complex possibly corresponds to a meta-stable transition state in Hfq-facilitated small RNA–mRNA annealing process. PMID:23605038

  7. Importance of biologically active aurora-like ultraviolet emission: stochastic irradiation of Earth and Mars by flares and explosions.

    PubMed

    Smith, David S; Scalo, John; Wheeler, J Craig

    2004-10-01

    Habitable planets will be subject to intense sources of ionizing radiation and fast particles from a variety of sources--from the host star to distant explosions--on a variety of timescales. Monte Carlo calculations of high-energy irradiation suggest that the surfaces of terrestrial-like planets with thick atmospheres (column densities greater than about 100 g cm(-2)) are well protected from directly incident X-rays and gamma-rays, but we find that sizeable fractions of incident ionizing radiation from astrophysical sources can be redistributed to biologically and chemically important ultraviolet wavelengths, a significant fraction of which can reach the surface. This redistribution is mediated by secondary electrons, resulting from Compton scattering and X-ray photoabsorption, the energies of which are low enough to excite and ionize atmospheric molecules and atoms, resulting in a rich aurora-like spectrum. We calculate the fraction of energy redistributed into biologically and chemically important wavelength regions for spectra characteristic of stellar flares and supernovae using a Monte-Carlo transport code and then estimate the fraction of this energy that is transmitted from the atmospheric altitudes of redistribution to the surface for a few illustrative cases. For atmospheric models corresponding to the Archean Earth, we assume no significant ultraviolet absorbers, only Rayleigh scattering, and find that the fraction of incident ionizing radiation that is received at the surface in the form of redistributed ultraviolet in the biologically relevant 200-320 nm region (UV-C and UV-B bands) can be up to 4%. On the present-day Earth with its ultraviolet ozone shield, this fraction is found to be 0.2%. Both values are many orders of magnitude higher than the fraction of direct ionizing radiation reaching the surface. This result implies that planetary organisms will be subject to mutationally significant, if intermittent, fluences of UV-B and harder radiation

  8. LPS structure and PhoQ activity are important for Salmonella Typhimurium virulence in the Galleria mellonella infection model [corrected].

    PubMed

    Bender, Jennifer K; Wille, Thorsten; Blank, Kathrin; Lange, Anna; Gerlach, Roman G

    2013-01-01

    The larvae of the wax moth, Galleria mellonella, have been used experimentally to host a range of bacterial and fungal pathogens. In this study we evaluated the suitability of G. mellonella as an alternative animal model of Salmonella infection. Using a range of inoculum doses we established that the LD₅₀ of SalmonellaTyphimurium strain NCTC 12023 was 3.6 × 10³ bacteria per larva. Further, a set of isogenic mutant strains depleted of known virulence factors was tested to identify determinants essential for S. Typhimurium pathogenesis. Mutants depleted of one or both of the type III secretion systems encoded by Salmonella Pathogenicity Islands 1 and 2 showed no virulence defect. In contrast, we observed reduced pathogenic potential of a phoQ mutant indicating an important role for the PhoPQ two-component signal transduction system. Lipopolysaccharide (LPS) structure was also shown to influence Salmonella virulence in G. mellonella. A waaL(rfaL) mutant, which lacks the entire O-antigen (OAg), was virtually avirulent, while a wzz(ST)/wzz(fepE) double mutant expressing only a very short OAg was highly attenuated for virulence. Furthermore, shortly after infection both LPS mutant strains showed decreased replication when compared to the wild type in a flow cytometry-based competitive index assay. In this study we successfully established a G. mellonella model of S. Typhimurium infection. By identifying PhoQ and LPS OAg length as key determinants of virulence in the wax moth larvae we proved that there is an overlap between this and other animal model systems, thus confirming that the G. mellonella infection model is suitable for assessing aspects of Salmonella virulence function.

  9. Activation of peroxisome proliferator-activated receptor γ (PPARγ) by nitroalkene fatty acids: importance of nitration position and degree of unsaturation

    PubMed Central

    Gorczynski, Michael J.; Smitherman, Pamela K.; Akiyama, Taro E.; Wood, Harold B.; Berger, Joel P.; King, S. Bruce; Morrow, Charles S.

    2009-01-01

    Nitroalkene fatty acids are potent endogenous ligand activators of PPARγ-dependent transcription. Previous studies with the naturally occurring regioisomers of nitrolinoleic acid revealed that the isomers are not equivalent with respect to PPARγ activation. To gain further insight into the structure-activity relationships between nitroalkenes and PPARγ, we examined additional naturally occurring nitroalkenes derived from oleic acid, 9-nitrooleic acid (E-9-NO2-18:1 [1]) and 10-nitrooleic acid (E-10-NO2-18:1 [2]), and several synthetic nitrated enoic fatty acids of variable carbon chain length, double bonds, and nitration site. At submicromolar concentrations, E-12-NO2 derivatives were considerably more potent than isomers nitrated at carbons 5, 6, 9, 10 or 13; and, chain length (16 versus 18) or number of double bonds (one versus two) was of little consequence for PPARγ activation. Interestingly, at higher concentrations (> 2 μM) the nitrated enoic fatty acids (E-9-NO2-18:1 [1], E-9-NO2-16:1 [3], E-10-NO2-18:1 [2], and E-12-NO2-18:1 [7]) deviated significantly from the saturable pattern of PPARγ activation observed for nitrated 1,4-dienoic fatty acids (E-9-NO2-18:2, E-10-NO2-18:2, E-12-NO2-18:2, and E-13-NO2-18:2). PMID:19719236

  10. Importance of cis determinants and nitrogenase activity in regulated stability of the Klebsiella pneumoniae nitrogenase structural gene mRNA.

    PubMed

    Simon, H M; Gosink, M M; Roberts, G P

    1999-06-01

    The Klebsiella pneumoniae nitrogen fixation (nif) mRNAs are unusually stable, with half-lives of 20 to 30 min under conditions favorable to nitrogen fixation (limiting nitrogen, anaerobiosis, temperatures of 30 degrees C). Addition of O2 or fixed nitrogen or temperature increases to 37 degrees C or more result in the dramatic destabilization of the nif mRNAs, decreasing the half-lives by a factor of 3 to 5. A plasmid expression system, independent of nif transcriptional regulation, was used to define cis determinants required for the regulated stability of the 5.2-kb nifHDKTY mRNA and to test the model suggested by earlier work that NifA is required in trans to stabilize nif mRNA under nif-derepressing conditions. O2 regulation of nifHDKTY mRNA stability is impaired in a plasmid containing a deletion of a 499-bp region of nifH, indicating that a site(s) required for the O2-regulated stability of the mRNA is located within this region. The simple model suggested from earlier work that NifA is required for stabilizing nif mRNA under conditions favorable for nitrogen fixation was disproved, and in its place, a more complicated model involving the sensing of nitrogenase activity as a component of the system regulating mRNA stability is proposed. Analysis of nifY mutants and overexpression suggests a possible involvement of the protein in this sensing process.

  11. Line-driven disk winds in active galactic nuclei: The critical importance of ionization and radiative transfer

    SciTech Connect

    Higginbottom, Nick; Knigge, Christian; Matthews, James H.; Proga, Daniel; Long, Knox S.; Sim, Stuart A.

    2014-07-01

    Accretion disk winds are thought to produce many of the characteristic features seen in the spectra of active galactic nuclei (AGNs) and quasi-stellar objects (QSOs). These outflows also represent a natural form of feedback between the central supermassive black hole and its host galaxy. The mechanism for driving this mass loss remains unknown, although radiation pressure mediated by spectral lines is a leading candidate. Here, we calculate the ionization state of, and emergent spectra for, the hydrodynamic simulation of a line-driven disk wind previously presented by Proga and Kallman. To achieve this, we carry out a comprehensive Monte Carlo simulation of the radiative transfer through, and energy exchange within, the predicted outflow. We find that the wind is much more ionized than originally estimated. This is in part because it is much more difficult to shield any wind regions effectively when the outflow itself is allowed to reprocess and redirect ionizing photons. As a result, the calculated spectrum that would be observed from this particular outflow solution would not contain the ultraviolet spectral lines that are observed in many AGN/QSOs. Furthermore, the wind is so highly ionized that line driving would not actually be efficient. This does not necessarily mean that line-driven winds are not viable. However, our work does illustrate that in order to arrive at a self-consistent model of line-driven disk winds in AGN/QSO, it will be critical to include a more detailed treatment of radiative transfer and ionization in the next generation of hydrodynamic simulations.

  12. Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles.

    PubMed

    Nchoutmboube, Jules A; Viktorova, Ekaterina G; Scott, Alison J; Ford, Lauren A; Pei, Zhengtong; Watkins, Paul A; Ernst, Robert K; Belov, George A

    2013-01-01

    All positive strand (+RNA) viruses of eukaryotes replicate their genomes in association with membranes. The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics, but our understanding of this process is very limited. Elements of autophagy and/or the secretory pathway were proposed to be hijacked for building of picornavirus replication organelles. However, even closely related viruses differ significantly in their requirements for components of these pathways. We demonstrate here that infection with diverse picornaviruses rapidly activates import of long chain fatty acids. While in non-infected cells the imported fatty acids are channeled to lipid droplets, in infected cells the synthesis of neutral lipids is shut down and the fatty acids are utilized in highly up-regulated phosphatidylcholine synthesis. Thus the replication organelles are likely built from de novo synthesized membrane material, rather than from the remodeled pre-existing membranes. We show that activation of fatty acid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3) as a novel host factor required for polio replication. Poliovirus protein 2A is required to trigger the activation of import of fatty acids independent of its protease activity. Shift in fatty acid import preferences by infected cells results in synthesis of phosphatidylcholines different from those in uninfected cells, arguing that the viral replication organelles possess unique properties compared to the pre-existing membranes. Our data show how poliovirus can change the overall cellular membrane homeostasis by targeting one critical process. They explain earlier observations of increased phospholipid synthesis in infected cells and suggest a simple model of the structural development of the membranous scaffold of replication complexes of picorna-like viruses, that may be

  13. Imported malaria.

    PubMed

    Schultz, M G

    1974-01-01

    There have been 4 waves of imported malaria in the USA. They occurred during the colonization of the country and during the Second World War, the UN Police Action in Korea, and the Viet-Nam conflict. The first 3 episodes are briefly described and the data on imported malaria from Viet-Nam are discussed in detail.Endemic malaria is resurgent in many tropical countries and international travel is also on the rise. This increases the likelihood of malaria being imported from an endemic area and introduced into a receptive area. The best defence for countries threatened by imported malaria is a vigorous surveillance programme. The principles of surveillance are discussed and an example of their application is provided by a description of the methods used to conduct surveillance of malaria in the USA.

  14. A RAS oncogene imparts growth factor independence to myeloid cells that abnormally regulate protein kinase C: a nonautocrine transformation pathway.

    PubMed

    Boswell, H S; Nahreini, T S; Burgess, G S; Srivastava, A; Gabig, T G; Inhorn, L; Srour, E F; Harrington, M A

    1990-06-01

    The factor-dependent cell line FDC-P1 has been utilized as a model of interleukin 3 (IL-3)-dependent myeloid cell proliferation. However, it has been recently observed that active phorbol esters (e.g., phorbol 12-myristate 13-acetate) may entirely replace IL-3 to promote its proliferation. These observations reveal abnormal regulation of protein kinase C (pkC) (absence of downregulation or overexpression). This property allowed a test of the hypothesis that the T24 RAS (codon 12) oncogene acts by constitutive and persistent pkC activation, driving proliferation. FDC-P1 cells were transfected by electroporation with the T24 RAS-containing vector pAL 8, or with a control vector pSVX Zip Neo, and neomycin-resistant clones were selected. Multiple RAS-transfectant clones were categorized for their growth factor requirement and incorporation of the 6.6-kb human mutant H-RAS genome. IL-3-independent clones had incorporated multiple (more than two) copies of the entire 6.6-kb RAS genome. The incorporation of multiple 6.6-kb RAS genomes was correlated with high-level p21 RAS expression. No evidence for autostimulatory growth factor production by clones containing the RAS oncogene was observed. Thus, acquisition of growth factor independence in myeloid cells by abundant expression of a RAS oncogene is linked, in part, to abnormal regulation of pkC, which acts as a collaborating oncogene.

  15. Application of the Collision-Imparted Velocity Method for Analyzing the Responses of Containment and Deflector Structures to Engine Rotor Fragment Impact

    NASA Technical Reports Server (NTRS)

    Collins, T. P.; Witmer, E. A.

    1973-01-01

    An approximate analysis, termed the Collision Imparted Velocity Method (CIVM), was employed for predicting the transient structural responses of containment rings or deflector rings which are subjected to impact from turbojet-engine rotor burst fragments. These 2-d structural rings may be initially circular or arbitrarily curved and may have either uniform or variable thickness; elastic, strain hardening, and strain rate material properties are accommodated. This approximate analysis utilizes kinetic energy and momentum conservation relations in order to predict the after-impact velocities of the fragment and the impacted ring segment. This information is then used in conjunction with a finite element structural response computation code to predict the transient, large deflection responses of the ring. Similarly, the equations of motion for each fragment are solved in small steps in time. Also, some comparisons of predictions with experimental data for fragment-impacted free containment rings are presented.

  16. A Brief Review of Research Using Near-Infrared Spectroscopy to Measure Activation of the Prefrontal Cortex during Emotional Processing: The Importance of Experimental Design

    PubMed Central

    Bendall, Robert C. A.; Eachus, Peter; Thompson, Catherine

    2016-01-01

    During the past two decades there has been a pronounced increase in the number of published research studies that have employed near-infrared spectroscopy (NIRS) to measure neural activation. The technique is now an accepted neuroimaging tool adopted by cognitive neuroscientists to investigate a number of fields, one of which is the study of emotional processing. Crucially, one brain region that is important to the processing of emotional information is the prefrontal cortex (PFC) and NIRS is ideally suited to measuring activity in this region. Compared to other methods used to record neural activation, NIRS reduces the discomfort to participants, makes data collection from larger sample sizes more achievable, and allows measurement of activation during tasks involving physical movement. However, the use of NIRS to investigate the links between emotion and cognition has revealed mixed findings. For instance, whilst some studies report increased PFC activity associated with the processing of negative information, others show increased activity in relation to positive information. Research shows differences in PFC activity between different cognitive tasks, yet findings also vary within similar tasks. This work reviews a selection of recent studies that have adopted NIRS to study PFC activity during emotional processing in both healthy individuals and patient populations. It highlights the key differences between research findings and argues that variations in experimental design could be a contributing factor to the mixed results. Guidance is provided for future work in this area in order to improve consistency within this growing field. PMID:27812329

  17. Role of the C-terminal extension peptide of plastid located glutamine synthetase from Medicago truncatula: Crucial for enzyme activity and needless for protein import into the plastids.

    PubMed

    Ferreira, Maria João; Vale, Diogo; Cunha, Luis; Melo, Paula

    2017-02-01

    Glutamine synthetase (GS), a key enzyme in plant nitrogen metabolism, is encoded by a small family of highly homologous nuclear genes that produce cytosolic (GS1) and plastidic (GS2) isoforms. Compared to GS1, GS2 proteins have two extension peptides, one at the N- and the other at the C-terminus, which show a high degree of conservation among plant species. It has long been known that the N-terminal peptide acts as a transit peptide, targeting the protein to the plastids however, the function of the C-terminal extension is still unknown. To investigate whether the C-terminal extension influences the activity of the enzyme, we produced a C-terminal truncated version of Medicago truncatula GS2a in Escherechia coli and studied its catalytic properties. The activity of the truncated protein was found to be lower than that of MtGS2a and with less affinity for glutamate. The importance of the C-terminal extension for the protein import into the chloroplast was also assessed by transient expression of fluorescently-tagged MtGS2a truncated at the C-terminus, which was correctly detected in the chloroplast. The results obtained in this work demonstrate that the C-terminal extension of M. truncatula GS2a is important for the activity of the enzyme and does not contain crucial information for the import process.

  18. HTLV-1 bZIP Factor RNA and Protein Impart Distinct Functions on T-cell Proliferation and Survival.

    PubMed

    Mitobe, Yuichi; Yasunaga, Jun-ichirou; Furuta, Rie; Matsuoka, Masao

    2015-10-01

    Infection of T cells with human T-cell leukemia virus type-1 (HTLV-1) induces clonal proliferation and is closely associated with the onset of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. Although Tax expression is frequently suppressed in HTLV-1-infected cells, the accessory gene, HTLV-1 bZIP factor (HBZ), is continuously expressed and has been implicated in HTLV-1 pathogenesis. Here, we report that transduction of mouse T cells with specific mutants of HBZ that distinguish between its RNA and protein activity results in differential effects on T-cell proliferation and survival. HBZ RNA increased cell number by attenuating apoptosis, whereas HBZ protein induced apoptosis. However, both HBZ RNA and protein promoted S-phase entry of T cells. We further identified that the first 50 bp of the HBZ coding sequence are required for RNA-mediated cell survival. Transcriptional profiling of T cells expressing wild-type HBZ, RNA, or protein revealed that HBZ RNA is associated with genes involved in cell cycle, proliferation, and survival, while HBZ protein is more closely related to immunological properties of T cells. Specifically, HBZ RNA enhances the promoter activity of survivin, an inhibitor of apoptosis, to upregulate its expression. Inhibition of survivin using YM155 resulted in impaired proliferation of several ATL cell lines as well as a T-cell line expressing HBZ RNA. The distinct functions of HBZ RNA and protein may have several implications for the development of strategies to control the proliferation and survival mechanisms associated with HTLV-1 infection and ATL.

  19. Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment.

    PubMed

    Borradaile, Nica M; Pickering, J Geoffrey

    2009-04-01

    Endothelial dysfunction is a characteristic of aging-related vascular disease and is worsened during diabetes. High glucose can impair endothelial cell (EC) function through cellular accumulation of reactive oxygen species, an insult that can also limit replicative lifespan. Nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF and visfatin, is rate-limiting for NAD+ salvage from nicotinamide and confers resistance to oxidative stress via SIRT1. We therefore sought to determine if Nampt expression could resist the detrimental effects of high glucose and confer a survival advantage to human vascular EC in this pathologic environment. Human aortic EC were infected with retrovirus encoding eGFP or eGFP-Nampt, and FACS-selected to yield populations with similar, modest transgene expression. Using a chronic glucose exposure model we tracked EC populations to senescence, assessed cellular metabolism, and determined in vitro angiogenic function. Overexpression of Nampt increased proliferation and extended replicative lifespan, and did so preferentially during glucose overload. Nampt expression delayed markers of senescence and limited reactive oxygen species accumulation in high glucose through a modest increase in aerobic glycolysis. Furthermore, tube networks formed by Nampt-overexpressing EC were more extensive and glucose-resistant, in accordance with SIRT1-mediated repression of the anti-angiogenic transcription factor, FoxO1. We conclude that Nampt enables proliferating human EC to resist the oxidative stress of aging and of high glucose, and to productively use excess glucose to support replicative longevity and angiogenic activity. Enhancing endothelial Nampt activity may thus be beneficial in scenarios requiring EC-based vascular repair and regeneration during aging and hyperglycemia, such as atherosclerosis and diabetes-related vascular disease.

  20. Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

    PubMed Central

    Schoberle, Taylor J.; Chung, Lawton K.; McPhee, Joseph B.; Bogin, Ben

    2016-01-01

    Pathogenic Yersinia species utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promote Yersinia pathogenesis. In turn, Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior to Yersinia pseudotuberculosis infection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of a Y. pseudotuberculosis yopM mutant was compared to that of a yopJ yopM, yopE yopM, yopH yopM, yopT yopM, or ypkA yopM mutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutant Y. pseudotuberculosis strains. Results show enhanced activation of caspase-1 after infection with the yopJ yopM mutant relative to infection by any other single or double mutant. Similar results were obtained with the yopJ, yopM, and yopJ yopM mutants of Yersinia pestis. Following intravenous infection of mice, the Y. pseudotuberculosis yopJ mutant was as virulent as the wild type, while the yopJ yopM mutant was significantly more attenuated than the yopM mutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promoting Yersinia virulence. PMID:26810037

  1. Testing the impact of virus importation rates and future climate change on dengue activity in Malaysia using a mechanistic entomology and disease model.

    PubMed

    Williams, C R; Gill, B S; Mincham, G; Mohd Zaki, A H; Abdullah, N; Mahiyuddin, W R W; Ahmad, R; Shahar, M K; Harley, D; Viennet, E; Azil, A; Kamaluddin, A

    2015-10-01

    We aimed to reparameterize and validate an existing dengue model, comprising an entomological component (CIMSiM) and a disease component (DENSiM) for application in Malaysia. With the model we aimed to measure the effect of importation rate on dengue incidence, and to determine the potential impact of moderate climate change (a 1 °C temperature increase) on dengue activity. Dengue models (comprising CIMSiM and DENSiM) were reparameterized for a simulated Malaysian village of 10 000 people, and validated against monthly dengue case data from the district of Petaling Jaya in the state of Selangor. Simulations were also performed for 2008-2012 for variable virus importation rates (ranging from 1 to 25 per week) and dengue incidence determined. Dengue incidence in the period 2010-2012 was modelled, twice, with observed daily weather and with a 1 °C increase, the latter to simulate moderate climate change. Strong concordance between simulated and observed monthly dengue cases was observed (up to r = 0·72). There was a linear relationship between importation and incidence. However, a doubling of dengue importation did not equate to a doubling of dengue activity. The largest individual dengue outbreak was observed with the lowest dengue importation rate. Moderate climate change resulted in an overall decrease in dengue activity over a 3-year period, linked to high human seroprevalence early on in the simulation. Our results suggest that moderate reductions in importation with control programmes may not reduce the frequency of large outbreaks. Moderate increases in temperature do not necessarily lead to greater dengue incidence.

  2. Structural units important for activity of a novel-type phosphoserine phosphatase from Hydrogenobacter thermophilus TK-6 revealed by crystal structure analysis.

    PubMed

    Chiba, Yoko; Horita, Shoichiro; Ohtsuka, Jun; Arai, Hiroyuki; Nagata, Koji; Igarashi, Yasuo; Tanokura, Masaru; Ishii, Masaharu

    2013-04-19

    Novel-type serine-synthesizing enzymes, termed metal-independent phosphoserine phosphatases (iPSPs), were recently identified and characterized from Hydrogenobacter thermophilus, a chemolithoautotrophic bacterium belonging to the order Aquificales. iPSPs are cofactor-dependent phosphoglycerate mutase (dPGM)-like phosphatases that have significant amino acid sequence similarity to dPGMs but lack phosphoglycerate mutase activity. Genes coding dPGM-like phosphatases have been identified in a broad range of organisms; however, predicting the function of the corresponding proteins based on sequence information alone is difficult due to their diverse substrate preferences. Here, we determined the crystal structure of iPSP1 from H. thermophilus in the apo-form and in complex with its substrate L-phosphoserine to find structural units important for its phosphatase activity toward L-phosphoserine. Structural and biochemical characterization of iPSP1 revealed that the side chains of His(85) and C-terminal region characteristic of iPSP1 are responsible for the PSP activity. The importance of these structural units for PSP activity was confirmed by high PSP activity observed in two novel dPGM-like proteins from Cyanobacteria and Chloroflexus in which the two structural units were conserved. We anticipate that our present findings will facilitate understanding of the serine biosynthesis pathways of organisms that lack gene(s) encoding conventional PSPs, as the structural information revealed here will help to identify iPSP from sequence databases.

  3. A Conserved Aspartic Acid Is Important for Agonist (VUAA1) and Odorant/Tuning Receptor-Dependent Activation of the Insect Odorant Co-Receptor (Orco)

    PubMed Central

    Kumar, Brijesh N.; Taylor, Robert W.; Pask, Gregory M.; Zwiebel, Laurence J.; Newcomb, Richard D.; Christie, David L.

    2013-01-01

    Insect odorant receptors function as heteromeric odorant-gated cation channels comprising a conventional odorant-sensitive tuning receptor, and a conserved co-receptor (Orco). An Orco agonist, VUAA1, is able to activate both heteromeric and homomeric Orco-containing channels. Very little is known about specific residues in Orco that contribute to cation permeability and gating. We investigated the importance of two conserved Asp residues, one in each of transmembrane domains 5 and 7, for channel function by mutagenesis. Drosophila melanogaster Orco and its substitution mutants were expressed in HEK cells and VUAA1-stimulated channel activity was determined by Ca2+ influx and whole-cell patch clamp electrophysiology. Substitution of D466 in transmembrane 7 with amino acids other than glutamic acid resulted in a substantial reduction in channel activity. The D466E Orco substitution mutant was ∼2 times more sensitive to VUAA1. The permeability of the D466E Orco mutant to cations was unchanged relative to wild-type Orco. When D466E Orco is co-expressed with a conventional tuning odorant receptor, the heteromeric complex also shows increased sensitivity to an odorant. Thus, the effect of the D466E mutation is not specific to VUAA1 agonism or dependent on homomeric Orco assembly. We suggest the gain-of-activation characteristic of the D466E mutant identifies an amino acid that is likely to be important for activation of both heteromeric and homomeric insect odorant receptor channels. PMID:23894621

  4. Correlation between Coulomb stress changes imparted by large historical strike-slip earthquakes and current seismicity in Japan

    NASA Astrophysics Data System (ADS)

    Ishibe, Takeo; Shimazaki, Kunihiko; Tsuruoka, Hiroshi; Yamanaka, Yoshiko; Satake, Kenji

    2011-03-01

    To determine whether current seismicity continues to be affected by large historical earthquakes, we investigated the correlation between current seismicity in Japan and the static stress changes in the Coulomb Failure Function (ΔCFF) due to eight large historical earthquakes (since 1923, magnitude ≥ 6.5) with a strike-slip mechanism. The ΔCFF was calculated for two types of receiver faults: the mainshock and the focal mechanisms of recent moderate earthquakes. We found that recent seismicity for the mainshock receiver faults is concentrated in the positive ΔCFF regions of four earthquakes (the 1927 Tango, 1943 Tottori, 1948 Fukui, and 2000 Tottori-Ken Seibu earthquakes), while no such correlations are recognizable for the other four earthquakes (the 1931 Nishi-Saitama, 1963 Wakasa Bay, 1969 Gifu-Ken Chubu, and 1984 Nagano-Ken Seibu earthquakes). The probability distribution of the ΔCFF calculated for the recent focal mechanisms clearly indicates that recent earthquakes concentrate in positive ΔCFF regions, suggesting that the current seismicity may be affected by a number of large historical earthquakes. The proposed correlation between the ΔCFF and recent seismicity may be affected by multiple factors controlling aftershock activity or decay time.

  5. An engineered right-handed coiled coil domain imparts extreme thermostability to the KcsA channel.

    PubMed

    Yuchi, Zhiguang; Pau, Victor P T; Lu, Bridget X; Junop, Murray; Yang, Daniel S C

    2009-11-01

    KcsA, a potassium channel from Streptomyces lividans, was the first ion channel to have its transmembrane domain structure determined by crystallography. Previously we have shown that its C-terminal cytoplasmic domain is crucial for the thermostability and the expression of the channel. Expression was almost abolished in its absence, but could be rescued by the presence of an artificial left-handed coiled coil tetramerization domain GCN4. In this study, we noticed that the handedness of GCN4 is not the same as the bundle crossing of KcsA. Therefore, a compatible right-handed coiled coil structure was identified from the Protein Data Bank and used to replace the C-terminal domain of KcsA. The hybrid channel exhibited a higher expression level than the wild-type and is extremely thermostable. Surprisingly, this stable hybrid channel is equally active as the wild-type channel in conducting potassium ions through a lipid bilayer at an acidic pH. We suggest that a similar engineering strategy could be applied to other ion channels for both functional and structural studies.

  6. A Superhelical Spiral in the Escherichia coli DNA Gyrase A C-terminal Domain Imparts Unidirectional Supercoiling Bias

    SciTech Connect

    Ruthenburg,A.; Graybosch, D.; Huetsch, J.; Verdine, G.

    2005-01-01

    DNA gyrase is unique among type II topoisomerases in that its DNA supercoiling activity is unidirectional. The C-terminal domain of the gyrase A subunit (GyrA-CTD) is required for this supercoiling bias. We report here the x-ray structure of the Escherichia coli GyrA-CTD (Protein Data Bank code 1ZI0). The E. coli GyrA-CTD adopts a circular-shaped {beta}-pinwheel fold first seen in the Borrelia burgdorferi GyrA-CTD. However, whereas the B. burgdorferi GyrA-CTD is flat, the E. coli GyrA-CTD is spiral. DNA relaxation assays reveal that the E. coli GyrA-CTD wraps DNA inducing substantial (+) superhelicity, while the B. burgdorferi GyrA-CTD introduces a more modest (+) superhelicity. The observation of a superhelical spiral in the present structure and that of the Bacillus stearothermophilus ParC-CTD structure suggests unexpected similarities in substrate selectivity between gyrase and Topo IV enzymes. We propose a model wherein the right-handed ((+) solenoidal) wrapping of DNA around the E. coli GyrA-CTD enforces unidirectional (-) DNA supercoiling.

  7. Halopriming of seeds imparts tolerance to NaCl and PEG induced stress in Vigna radiata (L.) Wilczek varieties.

    PubMed

    Jisha, K C; Puthur, Jos T

    2014-07-01

    The investigation was carried out to study the effect of halopriming on NaCl and polyethylene glycol-6000 (PEG-6000) induced stress tolerance potential of three Vigna radiata (L.) Wilczek varieties, with varied abiotic stress tolerance potential. Halopriming is a seed priming technique in which the seeds were soaked in various salt solutions (in this study NaCl was used). The results of the study indicated that the application of stresses (both NaCl and PEG) induced retardation of growth attributes (measured in terms of shoot length, fresh weight, dry weight) and decrease in physiological attributes like total chlorophyll content, metabolites, photosynthetic and mitochondrial activity of the seedlings in all three V. radiata (L.) varieties. However, halopriming of the seeds could reduce the extent of decrease in these biological attributes. NaCl and PEG stress also caused increase in MDA content (a product of membrane lipid peroxidation) in all the varieties studied and this increase was significantly minimized under halopriming. From the present investigation it was evident that among the green gram varieties studied, Pusa Vishal, a NaCl tolerant variety showed enhanced tolerance to NaCl and PEG induced stress, when the seeds were subjected to halopriming followed by Pusa Ratna (stress sensitive variety). Pusa 9531 (drought tolerant variety) also showed positive halopriming effects but it was less significant when compared to other two varieties. It could be concluded that halopriming improved the drought and salinity stress tolerance potential of all varieties and it was significantly higher in the Pusa Vishal as compared to Pusa 9531 and Pusa Ratna.

  8. Functionalised nanoscale coatings using layer-by-layer assembly for imparting antibacterial properties to polylactide-co-glycolide surfaces.

    PubMed

    Gentile, Piergiorgio; Frongia, Maria E; Cardellach, Mar; Miller, Cheryl A; Stafford, Graham P; Leggett, Graham J; Hatton, Paul V

    2015-07-01

    In order to achieve high local biological activity and reduce the risk of side effects of antibiotics in the treatment of periodontal and bone infections, a localised and temporally controlled delivery system is desirable. The aim of this research was to develop a functionalised and resorbable surface to contact soft tissues to improve the antibacterial behaviour during the first week after its implantation in the treatment of periodontal and bone infections. Solvent-cast poly(d,l-lactide-co-glycolide acid) (PLGA) films were aminolysed and then modified by Layer-by-Layer technique to obtain a nano-layered coating using poly(sodium4-styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) as polyelectrolytes. The water-soluble antibiotic, metronidazole (MET), was incorporated from the ninth layer. Infrared spectroscopy showed that the PSS and PAH absorption bands increased with the layer number. The contact angle values had a regular alternate behaviour from the ninth layer. X-ray Photoelectron Spectroscopy evidenced two distinct peaks, N1s and S2p, indicating PAH and PSS had been introduced. Atomic Force Microscopy showed the presence of polyelectrolytes on the surface with a measured roughness about 10nm after 20 layers' deposition. The drug release was monitored by Ultraviolet-visible spectroscopy showing 80% loaded-drug delivery in 14 days. Finally, the biocompatibility was evaluated in vitro with L929 mouse fibroblasts and the antibacterial properties were demonstrated successfully against the keystone periodontal bacteria Porphyromonas gingivalis, which has an influence on implant failure, without compromising in vitro biocompatibility. In this study, PLGA was successfully modified to obtain a localised and temporally controlled drug delivery system, demonstrating the potential value of LbL as a coating technology for the manufacture of medical devices with advanced functional properties.

  9. Improving Hiroshima Air-Over-Ground Thermal/Epithermal Activation Calculations Using a MUSH Model to Show the Importance of Local Shielding

    SciTech Connect

    Pace, J.V.

    2002-02-14

    Achieving agreement between measured and calculated neutron activation data resulting from Hiroshima and Nagasaki A-bomb detonations has been a major problem since the early 1980's. This has been particularly true for the materials that are activated by thermal and epithermal neutrons. Since thermal and epithermal neutrons are not transported very far from the weapon, the local shielding environment around the measurement location can be very important. A set of calculations incorporating an average density local-environment material (mush) has been made to demonstrate that the local environment plays an important role in the calculation-measurement agreement process. The optimum solution would be to include the local environment in all thermal neutron response calculations.

  10. Slow Climate Velocities in Mountain Streams Impart Thermal Resistance to Cold-Water Refugia Across the West

    NASA Astrophysics Data System (ADS)

    Isaak, D.; Young, M.; Luce, C.; Hostetler, S.; Wenger, S. J.; Peterson, E.; Ver Hoef, J.

    2015-12-01

    Mountain streams provide important headwater refugia for native fish, amphibians, and other cold-water fauna globally. Although the well documented existence of such refugia indicates some level of resistance to ongoing environmental change, stream warming associated with climate change raises questions about their future persistence. Moreover, evidence exists that air temperatures are warming faster at higher elevations, and some stream temperature models predict that cold streams associated with snowmelt hydrologies will be most sensitive to air temperature increases (i.e. high ratio of stream Δ˚C:air Δ˚C). Here, we estimate stream sensitivities to climate forcing using long-term monitoring records from 927 sites across the topographically complex northwestern U.S. Sensitivity values are combined with high-resolution NorWeST stream temperature scenarios (website: http://www.fs.fed.us/rm/boise/AWAE/projects/NorWeST.html) to map climate velocities at 1 kilometer resolution throughout the 450,000 stream kilometers in the regional network. Our results suggest that cold mountain streams are often 'double buffered' against the thermal effects of climate change due to low sensitivities (0.3ºC/ºC) and steep gradients, which translated to very slow climate velocities (<0.35 km/decade for streams >3% slope) from 1968-2011 when air temperatures warmed at the rate of 0.2ºC/decade. Alternative scenarios based on aggressive air temperature warming rates (2x historical rates) and higher sensitivity values of cold streams suggests velocities will remain low in mountain streams due to the dominant effects of steep channel slope and strong local temperature gradients. These results reinforce earlier predictions from high-resolution species distribution models that show which watersheds are most likely to host resilient native trout populations across the West later this century (Climate Shield project website: http://www.fs

  11. TLR9 played a more important role than TLR2 in the combination of maltose-binding protein and BCG-induced Th1 activation.

    PubMed

    Ni, Weihua; Wang, Fang; Liu, Guomu; Zhang, Nannan; Yuan, Hongyan; Jie, Jing; Tai, Guixiang

    2016-11-01

    Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4(+) T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy.

  12. The N-terminal hybrid binding domain of RNase HI from Thermotoga maritima is important for substrate binding and Mg2+-dependent activity.

    PubMed

    Jongruja, Nujarin; You, Dong-Ju; Kanaya, Eiko; Koga, Yuichi; Takano, Kazufumi; Kanaya, Shigenori

    2010-11-01

    Thermotoga maritima ribonuclease H (RNase H) I (Tma-RNase HI) contains a hybrid binding domain (HBD) at the N-terminal region. To analyze the role of this HBD, Tma-RNase HI, Tma-W22A with the single mutation at the HBD, the C-terminal RNase H domain (Tma-CD) and the N-terminal domain containing the HBD (Tma-ND) were overproduced in Escherichia coli, purified and biochemically characterized. Tma-RNase HI prefers Mg(2+) to Mn(2+) for activity, and specifically loses most of the Mg(2+)-dependent activity on removal of the HBD and 87% of it by the mutation at the HBD. Tma-CD lost the ability to suppress the RNase H deficiency of an E. coli rnhA mutant, indicating that the HBD is responsible for in vivo RNase H activity. The cleavage-site specificities of Tma-RNase HI are not significantly changed on removal of the HBD, regardless of the metal cofactor. Binding analyses of the proteins to the substrate using surface plasmon resonance indicate that the binding affinity of Tma-RNase HI is greatly reduced on removal of the HBD or the mutation. These results indicate that there is a correlation between Mg(2+)-dependent activity and substrate binding affinity. Tma-CD was as stable as Tma-RNase HI, indicating that the HBD is not important for stability. The HBD of Tma-RNase HI is important not only for substrate binding, but also for Mg(2+)-dependent activity, probably because the HBD affects the interaction between the substrate and enzyme at the active site, such that the scissile phosphate group of the substrate and the Mg(2+) ion are arranged ideally.

  13. Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNAiMet Turnover in Saccharomyces cerevisiae and Mtr4p Enzymatic Activities In Vitro.

    PubMed

    Li, Yan; Burclaff, Joseph; Anderson, James T

    2016-01-01

    RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities.

  14. [Imported histoplasmosis].

    PubMed

    Stete, Katarina; Kern, Winfried V; Rieg, Siegbert; Serr, Annerose; Maurer, Christian; Tintelnot, Kathrin; Wagner, Dirk

    2015-06-01

    Infections with Histoplasma capsulatum are rare in Germany, and mostly imported from endemic areas. Infections can present as localized or disseminated diseases in immunocompromised as well as immunocompetent hosts. A travel history may be a major clue for diagnosing histoplasmosis. Diagnostic tools include histology, cultural and molecular detection as well as serology. Here we present four cases of patients diagnosed and treated in Freiburg between 2004 and 2013 that demonstrate the broad range of clinical manifestations of histoplasmosis: an immunocompetent patient with chronic basal meningitis; a patient with HIV infection and fatal disseminated disease; a patient with pulmonary and cutaneous disease and mediastinal and cervical lymphadenopathy; and an immunosuppressed patient with disseminated involvement of lung, bone marrow and adrenal glands.

  15. Motor patterns of the small intestine explained by phase-amplitude coupling of two pacemaker activities: the critical importance of propagation velocity.

    PubMed

    Huizinga, Jan D; Parsons, Sean P; Chen, Ji-Hong; Pawelka, Andrew; Pistilli, Marc; Li, Chunpei; Yu, Yuanjie; Ye, Pengfei; Liu, Qing; Tong, Mengting; Zhu, Yong Fang; Wei, Defei

    2015-09-15

    Phase-amplitude coupling of two pacemaker activities of the small intestine, the omnipresent slow wave activity generated by interstitial cells of Cajal of the myenteric plexus (ICC-MP) and the stimulus-dependent rhythmic transient depolarizations generated by ICC of the deep muscular plexus (ICC-DMP), was recently hypothesized to underlie the orchestration of the segmentation motor pattern. The aim of the present study was to increase our understanding of phase-amplitude coupling through modeling. In particular the importance of propagation velocity of the ICC-DMP component was investigated. The outcome of the modeling was compared with motor patterns recorded from the rat or mouse intestine from which propagation velocities within the different patterns were measured. The results show that the classical segmentation motor pattern occurs when the ICC-DMP component has a low propagation velocity (<0.05 cm/s). When the ICC-DMP component has a propagation velocity in the same order of magnitude as that of the slow wave activity (∼1 cm/s), cluster type propulsive activity occurs which is in fact the dominant propulsive activity of the intestine. Hence, the only difference between the generation of propagating cluster contractions and the Cannon-type segmentation motor pattern is the propagation velocity of the low-frequency component, the rhythmic transient depolarizations originating from the ICC-DMP. Importantly, the proposed mechanism explains why both motor patterns have distinct rhythmic waxing and waning of the amplitude of contractions. The hypothesis is brought forward that the velocity is modulated by neural regulation of gap junction conductance within the ICC-DMP network.

  16. Motor patterns of the small intestine explained by phase-amplitude coupling of two pacemaker activities: the critical importance of propagation velocity

    PubMed Central

    Parsons, Sean P.; Chen, Ji-Hong; Pawelka, Andrew; Pistilli, Marc; Li, Chunpei; Yu, Yuanjie; Ye, Pengfei; Liu, Qing; Tong, Mengting; Zhu, Yong Fang; Wei, Defei

    2015-01-01

    Phase-amplitude coupling of two pacemaker activities of the small intestine, the omnipresent slow wave activity generated by interstitial cells of Cajal of the myenteric plexus (ICC-MP) and the stimulus-dependent rhythmic transient depolarizations generated by ICC of the deep muscular plexus (ICC-DMP), was recently hypothesized to underlie the orchestration of the segmentation motor pattern. The aim of the present study was to increase our understanding of phase-amplitude coupling through modeling. In particular the importance of propagation velocity of the ICC-DMP component was investigated. The outcome of the modeling was compared with motor patterns recorded from the rat or mouse intestine from which propagation velocities within the different patterns were measured. The results show that the classical segmentation motor pattern occurs when the ICC-DMP component has a low propagation velocity (<0.05 cm/s). When the ICC-DMP component has a propagation velocity in the same order of magnitude as that of the slow wave activity (∼1 cm/s), cluster type propulsive activity occurs which is in fact the dominant propulsive activity of the intestine. Hence, the only difference between the generation of propagating cluster contractions and the Cannon-type segmentation motor pattern is the propagation velocity of the low-frequency component, the rhythmic transient depolarizations originating from the ICC-DMP. Importantly, the proposed mechanism explains why both motor patterns have distinct rhythmic waxing and waning of the amplitude of contractions. The hypothesis is brought forward that the velocity is modulated by neural regulation of gap junction conductance within the ICC-DMP network. PMID:26135802

  17. Proteasome activity is important for replication recovery, CHK1 phosphorylation and prevention of G2 arrest after low-dose formaldehyde

    SciTech Connect

    Ortega-Atienza, Sara; Green, Samantha E.; Zhitkovich, Anatoly

    2015-07-15

    Formaldehyde (FA) is a human carcinogen with numerous sources of environmental and occupational exposures. This reactive aldehyde is also produced endogenously during metabolism of drugs and other processes. DNA–protein crosslinks (DPCs) are considered to be the main genotoxic lesions for FA. Accumulating evidence suggests that DPC repair in high eukaryotes involves proteolysis of crosslinked proteins. Here, we examined a role of the main cellular proteolytic machinery proteasomes in toxic responses of human lung cells to low FA doses. We found that transient inhibition of proteasome activity increased cytotoxicity and diminished clonogenic viability of FA-treated cells. Proteasome inactivation exacerbated suppressive effects of FA on DNA replication and increased the levels of the genotoxic stress marker γ-H2AX in normal human cells. A transient loss of proteasome activity in FA-exposed cells also caused delayed perturbations of cell cycle, which included G2 arrest and a depletion of S-phase populations at FA doses that had no effects in control cells. Proteasome activity diminished p53-Ser15 phosphorylation but was important for FA-induced CHK1 phosphorylation, which is a biochemical marker of DPC proteolysis in replicating cells. Unlike FA, proteasome inhibition had no effect on cell survival and CHK1 phosphorylation by the non-DPC replication stressor hydroxyurea. Overall, we obtained evidence for the importance of proteasomes in protection of human cells against biologically relevant doses of FA. Biochemically, our findings indicate the involvement of proteasomes in proteolytic repair of DPC, which removes replication blockage by these highly bulky lesions. - Highlights: • Proteasome inhibition enhances cytotoxicity of low-dose FA in human lung cells. • Active proteasomes diminish replication-inhibiting effects of FA. • Proteasome activity prevents delayed G2 arrest in FA-treated cells. • Proteasome inhibition exacerbates replication stress by FA in

  18. TALE1 from Xanthomonas axonopodis pv. manihotis acts as a transcriptional activator in plant cells and is important for pathogenicity in cassava plants.

    PubMed

    Castiblanco, Luisa F; Gil, Juliana; Rojas, Alejandro; Osorio, Daniela; Gutiérrez, Sonia; Muñoz-Bodnar, Alejandra; Perez-Quintero, Alvaro L; Koebnik, Ralf; Szurek, Boris; López, Camilo; Restrepo, Silvia; Verdier, Valérie; Bernal, Adriana J

    2013-01-01

    Many plant-pathogenic bacteria suppress pathogen-associated molecular pattern (PAMP)-triggered immunity by injecting effector proteins into the host cytoplasm during infection through the type III secretion system (TTSS). This type III secretome plays an important role in bacterial pathogenicity in susceptible hosts. Xanthomonas axonopodis pv. manihotis (Xam), the causal agent of cassava bacterial blight, injects several effector proteins into the host cell, including TALE1(Xam) . This protein is a member of the Transcriptional Activator-Like effector (TALE) protein family, formerly known as the AvrBs3/PthA family. TALE1(Xam) has 13.5 tandem repeats of 34 amino acids each, as well as two nuclear localization signals and an acidic activation domain at the C-terminus. In this work, we demonstrate the importance of TALE1(Xam) in the pathogenicity of Xam. We use versions of the gene that lack different domains in the protein in structure-function studies to show that the eukaryotic domains at the 3' end are critical for pathogenicity. In addition, we demonstrate that, similar to the characterized TALE proteins from other Xanthomonas species, TALE1(Xam) acts as a transcriptional activator in plant cells. This is the first report of the identification of a TALE in Xam, and contributes to our understanding of the pathogenicity mechanisms employed by this bacterium to colonize and cause disease in cassava.

  19. Stress imparted by the great 2004 Sumatra earthquake shut down transforms and activated rifts up to 400 km away in the Andaman Sea

    USGS Publications Warehouse

    Sevilgen, Volkan; Stein, Ross S.; Pollitz, Fred F.

    2012-01-01

    The origin and prevalence of triggered seismicity and remote aftershocks are under debate. As a result, they have been excluded from probabilistic seismic hazard assessment and aftershock hazard notices. The 2004 M = 9.2 Sumatra earthquake altered seismicity in the Andaman backarc rift-transform system. Here we show that over a 300-km-long largely transform section of the backarc, M ≥ 4.5 earthquakes stopped for five years, and over a 750-km-long backarc section, the rate of transform events dropped by two-thirds, while the rate of rift events increased eightfold. We compute the propagating dynamic stress wavefield and find the peak dynamic Coulomb stress is similar on the rifts and transforms. Long-period dynamic stress amplitudes, which are thought to promote dynamic failure, are higher on the transforms than on the rifts, opposite to the observations. In contrast to the dynamic stress, we calculate that the mainshock brought the transform segments approximately 0.2 bar (0.02 MPa) farther from static Coulomb failure and the rift segments approximately 0.2 bar closer to static failure, consistent with the seismic observations. This accord means that changes in seismicity rate are sufficiently predictable to be included in post-mainshock hazard evaluations.

  20. Stress imparted by the great 2004 Sumatra earthquake shut down transforms and activated rifts up to 400 km away in the Andaman Sea

    PubMed Central

    Sevilgen, Volkan; Stein, Ross S.; Pollitz, Fred F.

    2012-01-01

    The origin and prevalence of triggered seismicity and remote aftershocks are under debate. As a result, they have been excluded from probabilistic seismic hazard assessment and aftershock hazard notices. The 2004 M = 9.2 Sumatra earthquake altered seismicity in the Andaman backarc rift-transform system. Here we show that over a 300-km-long largely transform section of the backarc, M≥4.5 earthquakes stopped for five years, and over a 750-km-long backarc section, the rate of transform events dropped by two-thirds, while the rate of rift events increased eightfold. We compute the propagating dynamic stress wavefield and find the peak dynamic Coulomb stress is similar on the rifts and transforms. Long-period dynamic stress amplitudes, which are thought to promote dynamic failure, are higher on the transforms than on the rifts, opposite to the observations. In contrast to the dynamic stress, we calculate that the mainshock brought the transform segments approximately 0.2 bar (0.02 MPa) farther from static Coulomb failure and the rift segments approximately 0.2 bar closer to static failure, consistent with the seismic observations. This accord means that changes in seismicity rate are sufficiently predictable to be included in post-mainshock hazard evaluations. PMID:22949694

  1. Stress imparted by the great 2004 Sumatra earthquake shut down transforms and activated rifts up to 400 km away in the Andaman Sea.

    PubMed

    Sevilgen, Volkan; Stein, Ross S; Pollitz, Fred F

    2012-09-18

    The origin and prevalence of triggered seismicity and remote aftershocks are under debate. As a result, they have been excluded from probabilistic seismic hazard assessment and aftershock hazard notices. The 2004 M = 9.2 Sumatra earthquake altered seismicity in the Andaman backarc rift-transform system. Here we show that over a 300-km-long largely transform section of the backarc, M≥4.5 earthquakes stopped for five years, and over a 750-km-long backarc section, the rate of transform events dropped by two-thirds, while the rate of rift events increased eightfold. We compute the propagating dynamic stress wavefield and find the peak dynamic Coulomb stress is similar on the rifts and transforms. Long-period dynamic stress amplitudes, which are thought to promote dynamic failure, are higher on the transforms than on the rifts, opposite to the observations. In contrast to the dynamic stress, we calculate that the mainshock brought the transform segments approximately 0.2 bar (0.02 MPa) farther from static Coulomb failure and the rift segments approximately 0.2 bar closer to static failure, consistent with the seismic observations. This accord means that changes in seismicity rate are sufficiently predictable to be included in post-mainshock hazard evaluations.

  2. Stability and fragmentation of the activity rhythm across the sleep-wake cycle: the importance of age, lifestyle, and mental health.

    PubMed

    Luik, Annemarie I; Zuurbier, Lisette A; Hofman, Albert; Van Someren, Eus J W; Tiemeier, Henning

    2013-12-01

    The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96 h (138 ± 14 h, mean ± SD) were collected from 1734 people (age: 62 ± 9.4 yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β = 0.07, p = 0.02), but also with a more fragmented distribution of periods of activity and inactivity (β = 0.20, p < 0.001). Having more depressive symptoms was related to less stable (β = -0.07, p = 0.005) and more fragmented (β = 0.10, p < 0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β = -0.11, p < 0.001; smoking: β = -0.11, p < 0.001) and more fragmented rhythms (BMI: β = 0.09, p < 0.001; smoking: β = 0.11, p < 0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.

  3. Analytic Hierarchy Process to Define the Most Important Factors and Related Technologies for Empowering Elderly People in Taking an Active Role in their Health.

    PubMed

    Fico, G; Gaeta, E; Arredondo, M T; Pecchia, L

    2015-09-01

    Successful management of health conditions in older population is determined by strategic involvement of a professional team of careers and by empowering patients and their caregivers to take over a central role and responsibility in the daily management of condition. Identifying, structuring and ranking the most important needs related to these aspects could pave the way for improved strategies in designing systems and technological solutions supporting user empowerment. This paper presents the preliminary results of a study aiming to elicit these needs. Healthcare professionals, working together in the European and Innovation Partnership on Active and Healthy Ageing (EIP-AHA) initiative, have defined a set of needs and factors that have been organized in two hierarchies around the concepts of patient activation and proactive and prepared care team, defined in the Chronic Care Model. The two hierarchies have been mapped, by a team of experts in computer science, with technologies and solutions that could facilitate the achievement of the identified needs.

  4. Glycogen synthase kinase 3 activation is important for anthrax edema toxin-induced dendritic cell maturation and anthrax toxin receptor 2 expression in macrophages.

    PubMed

    Larabee, Jason L; Maldonado-Arocho, Francisco J; Pacheco, Sergio; France, Bryan; DeGiusti, Kevin; Shakir, Salika M; Bradley, Kenneth A; Ballard, Jimmy D

    2011-08-01

    Anthrax edema toxin (ET) is one of two binary toxins produced by Bacillus anthracis that contributes to the virulence of this pathogen. ET is an adenylate cyclase that generates high levels of cyclic AMP (cAMP), causing alterations in multiple host cell signaling pathways. We previously demonstrated that ET increases cell surface expression of the anthrax toxin receptors (ANTXR) in monocyte-derived cells and promotes dendritic cell (DC) migration toward the lymph node-homing chemokine MIP-3β. In this work, we sought to determine if glycogen synthase kinase 3 (GSK-3) is important for ET-induced modulation of macrophage and DC function. We demonstrate that inhibition of GSK-3 dampens ET-induced maturation and migration processes of monocyte-derived dendritic cells (MDDCs). Additional studies reveal that the ET-induced expression of ANTXR in macrophages was decreased when GSK-3 activity was disrupted with chemical inhibitors or with small interfering RNA (siRNA) targeting GSK-3. Further examination of the ET induction of ANTXR revealed that a dominant negative form of CREB could block the ET induction of ANTXR, suggesting that CREB or a related family member was involved in the upregulation of ANTXR. Because CREB and GSK-3 activity appeared to be important for ET-induced ANTXR expression, the impact of GSK-3 on ET-induced CREB activity was examined in RAW 264.7 cells possessing a CRE-luciferase reporter. As with ANTXR expression, the ET induction of the CRE reporter was decreased by reducing GSK-3 activity. These studies not only provide insight into host pathways targeted by ET but also shed light on interactions between GSK-3 and CREB pathways in host immune cells.

  5. Recognizing the importance of exposure-dose-response dynamics for ecotoxicity assessment: nitrofurazone-induced antioxidase activity and mRNA expression in model protozoan Euplotes vannus.

    PubMed

    Hong, Yazhen; Liu, Shuxing; Lin, Xiaofeng; Li, Jiqiu; Yi, Zhenzhen; Al-Rasheid, Khaled A S

    2015-06-01

    The equivocality of dose-response relationships has, in practice, hampered the application of biomarkers as a means to evaluate environmental risk, yet this important issue has not yet been fully recognized or explored. This paper evaluates the potential of antioxidant enzymes in the ciliated protozoan Euplotes vannus for use as biomarkers. Dose-response dynamics, together with both the enzyme activity and the gene expression of the antioxidant enzymes, superoxide dismutase, and glutathione peroxidase, were investigated when E. vannus were exposed to graded doses of nitrofurazone for several discrete durations. Mathematical models were explored to characterize the dose-response profiles and, specifically, to identify any equivocality in terms of endpoint. Significant differences were found in both enzyme activity and messenger RNA (mRNA) expression in the E. vannus treated with nitrofurazone, and the interactions between exposure dosage and duration were significant. Correlations between enzyme activity, mRNA expression, and nitrofurazone dose varied with exposure duration. Particularly, the dose-responses showed different dynamics depending on either endpoint or exposure duration. Our findings suggest that both the enzyme activity and the gene expression of the tested antioxidant enzymes can be used as biomarkers for ecotoxicological assessment on the premise of ascertaining appropriate dosage scope, exposure duration, endpoint, etc., which can be achieved by using dose-response dynamics.

  6. A Comprehensive Review on the Phytochemical Constituents and Pharmacological Activities of Pogostemon cablin Benth.: An Aromatic Medicinal Plant of Industrial Importance.

    PubMed

    Swamy, Mallappa Kumara; Sinniah, Uma Rani

    2015-05-12

    Pogostemon cablin Benth. (patchouli) is an important herb which possesses many therapeutic properties and is widely used in the fragrance industries. In traditional medicinal practices, it is used to treat colds, headaches, fever, nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In aromatherapy, patchouli oil is used to relieve depression, stress, calm nerves, control appetite and to improve sexual interest. Till now more than 140 compounds, including terpenoids, phytosterols, flavonoids, organic acids, lignins, alkaloids, glycosides, alcohols, aldehydes have been isolated and identified from patchouli. The main phytochemical compounds are patchouli alcohol, α-patchoulene, β-patchoulene, α-bulnesene, seychellene, norpatchoulenol, pogostone, eugenol and pogostol. Modern studies have revealed several biological activities such as antioxidant, analgesic, anti-inflammatory, antiplatelet, antithrombotic, aphrodisiac, antidepressant, antimutagenic, antiemetic, fibrinolytic and cytotoxic activities. However, some of the traditional uses need to be verified and may require standardizing and authenticating the bioactivity of purified compounds through scientific methods. The aim of the present review is to provide comprehensive knowledge on the phytochemistry and pharmacological activities of essential oil and different plant extracts of patchouli based on the available scientific literature. This information will provide a potential guide in exploring the use of main active compounds of patchouli in various medical fields.

  7. Does weather play an important role in the early nesting activity of colonial waterbirds? A case study in putrajaya wetlands, malaysia.

    PubMed

    Ismail, Ahmad; Rahman, Faid

    2013-08-01

    Environmental factors can play important roles in influencing waterbird communities. In particular, weather may have various biological and ecological impacts on the breeding activities of waterbirds, though most studies have investigated the effect of weather on the late stages of waterbird breeding (e.g., hatching rate, chick mortality). Conversely, the present study attempts to highlight the influence of weather on the early nesting activities of waterbirds by evaluating a recently established mixed-species colony in Putrajaya Wetlands, Malaysia. The results show that only rainfall and temperature have a significant influence on the species' nesting activities. Rainfall activity is significantly correlated with the Grey Heron's rate of establishment (rainfall: rs = 0.558, p = 0.03, n = 72) whereas both temperature and rainfall are associated with Painted Stork's nesting density (temperature: rs = 0.573, p = 0.013; rainfall: rs = -0.662, p = 0.03, n = 48). There is a possibility that variations in the rainfall and temperature provide a cue for the birds to initiate their nesting. Regardless, this paper addresses concerns on the limitations faced in the study and suggests long-term studies for confirmation.

  8. The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

    PubMed

    Callan, Akiko; Callan, Daniel; Ando, Hiroshi

    2017-02-01

    Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

  9. ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance for SecA2 function in macrophages.

    PubMed

    Hou, Jie M; D'Lima, Nadia G; Rigel, Nathan W; Gibbons, Henry S; McCann, Jessica R; Braunstein, Miriam; Teschke, Carolyn M

    2008-07-01

    The Sec-dependent translocation pathway that involves the essential SecA protein and the membrane-bound SecYEG translocon is used to export many proteins across the cytoplasmic membrane. Recently, several pathogenic bacteria, including Mycobacterium tuberculosis, were shown to possess two SecA homologs, SecA1 and SecA2. SecA1 is essential for general protein export. SecA2 is specific for a subset of exported proteins and is important for M. tuberculosis virulence. The enzymatic activities of two SecA proteins from the same microorganism have not been defined for any bacteria. Here, M. tuberculosis SecA1 and SecA2 are shown to bind ATP with high affinity, though the affinity of SecA1 for ATP is weaker than that of SecA2 or Escherichia coli SecA. Amino acid substitution of arginine or alanine for the conserved lysine in the Walker A motif of SecA2 eliminated ATP binding. We used the SecA2(K115R) variant to show that ATP binding was necessary for the SecA2 function of promoting intracellular growth of M. tuberculosis in macrophages. These results are the first to show the importance of ATPase activity in the function of accessory SecA2 proteins.

  10. Surfactant Protein A integrates activation signal strength to differentially modulate T cell proliferation

    PubMed Central

    Mukherjee, Sambuddho; Giamberardino, Charles; Thomas, Joseph; Evans, Kathy; Goto, Hisatsugu; Ledford, Julie G; Hsia, Bethany; Pastva, Amy M; Wright, Jo Rae

    2011-01-01

    Pulmonary surfactant lipoproteins lower the surface tension at the alveolar:airway interface of the lung and participate in host defense. Previous studies reported that surfactant protein A (SP-A) inhibits lymphocyte proliferation. We hypothesized that SP-A mediated modulation of T cell activation depends upon the strength, duration and type of lymphocyte activating signals. Modulation of T cell signal strength imparted by different activating agents ex and in vivo in different mouse models, and in vitro with human T cells show a strong correlation between strength of signal (SoS) and functional effects of SP-A interactions. T cell proliferation is enhanced in the presence of SP-A at low SoS imparted by exogenous mitogens, specific antibodies, APCs or in homeostatic proliferation. Proliferation is inhibited at higher SoS imparted by different doses of the same T cell mitogens, or indirect stimuli such as LPS. Importantly, reconstitution with exogenous SP-A into the lungs of SP-A-/- mice stimulated with a strong signal also resulted in suppression of T cell proliferation, while elevating baseline proliferation in unstimulated T cells. These signal strength and SP-A dependent effects are mediated by changes in intracellular Ca2+ levels over time, involving extrinsic Ca2+ activated channels late during activation. These effects are intrinsic to the global T cell population, and are manifested in vivo in naïve as well as memory phenotype T cells. Thus, SP-A appears to integrate signal thresholds to control T cell proliferation. PMID:22219327

  11. Semi-rational engineering of cytochrome P450sca-2 in a hybrid system for enhanced catalytic activity: insights into the important role of electron transfer.

    PubMed

    Ba, Lina; Li, Pan; Zhang, Hui; Duan, Yan; Lin, Zhanglin

    2013-11-01

    Hybrid P450 systems in which P450 monooxygenases are reconstituted with non-native or surrogate redox partners have become important for the engineering of this class of versatile enzymes. P450sca-2 from Streptomyces carbophilus stereoselectively hydroxylates mevastatin to yield pravastatin, a cholesterol-lowering drug. While S. carbophilus has been successfully applied in the industrial biotransformation process for pravastatin, the molecular study and engineering of P450sca-2 has been very limited. We have previously established a functional P450sca-2/Pdx/Pdr hybrid system. In this study, on the basis of a more active P450sca-2 mutant (R8-5C), five sites located in the substrate binding pocket, substrate access entrance, and presumed Pdx interaction interface were rationally chosen, and systematically subjected to site-directed saturation mutagenesis (SDSM), and three rounds of iterative saturation mutagenesis (ISM). A best mutant (Variant III) was obtained, which showed a whole cell biotransformation activity (377.5 mg/L) and an overall apparent k(cat) (6.37 min⁻¹) that was 7.1- and 10.0-fold that of the starting template R8-5C, respectively. Kinetic characterization revealed that most of the improvements seen for the SDSM and ISM mutants came from enhanced overall electron transfer, with the two sites at the interface between P450sca-2 and Pdx (T119 and N363) being most critical. Our study underscores the important role of electron transfer in a hybrid P450 system, and also demonstrates the utility of ISM in optimizing the redox partner interface. This should facilitate engineering of this and other important hybrid P450 systems.

  12. Importance of sports during youth and exercise barriers in 20- to 29-year-old male nonathletes differently motivated for regular physical activities.

    PubMed

    Leyk, Dieter; Witzki, Alexander; Sievert, Alexander; Rohde, Ulrich; Moedl, Anne; Rüther, Thomas; Löllgen, Herbert; Hackfort, Dieter

    2012-07-01

    The number of sedentary young adults has dramatically increased in past decades, and sedentary lifestyles are adopted at an increasingly earlier age. Little is known about barriers or predictors to (re)initiate regular physical activity in this group. The purpose of the study is to (a) identify subgroups in nonathletes differing in their amenability to physical exercise, (b) to analyze them for differences in barriers and intention to exercise, and (c) compare importance of sports during youth in nonathletes to trained peers. Using a health and fitness questionnaire 589 nonathletes were queried in the cross-sectional survey and compared with 270 trained peers. Athletic abstainers (A), lower (L), and higher (H) motivated nonathletes were separated based on previous engagement in sports. Of the nonathletes, 54.7% reported only 1 barrier to exercise. Although this feature was most prominent in H (71.5%), the other groups showed significantly more barriers and a broader distribution. Similar characteristics but minor differences were observed for perceived importance of sports during youth. The most significant differences between athletes and nonathletes emerged enquiring the attitude and activity of the parents. The majority of nonathletes (72.8%) indicate their intention to exercise in the future. Their intention differed significantly in H (88.1%), L (76.1%), and A (59.1%). However, there are good reasons to doubt that most of those intending nonathletes will actually become physically active. Even in the analyzed narrow age range of men different motivated groups of nonathletes were found. Because of the differences in receptiveness and approachability health promotion policies may not only consider the often recommended tailored interventions but also carefully designed incentive programs.

  13. Overweight and obese adolescent girls: the importance of promoting sensible eating and activity behaviors from the start of the adolescent period.

    PubMed

    Todd, Alwyn S; Street, Steven J; Ziviani, Jenny; Byrne, Nuala M; Hills, Andrew P

    2015-02-17

    The adolescent period is associated with changes in eating and activity behaviors in girls. Less reliance on parental provision and choice of food, coupled with a decrease in participation in physical activity and sport, can create an energy imbalance, predisposing to weight gain. Physiological alterations to body composition, reduction in insulin sensitivity, and psychological adjustments may further amplify the risk of becoming overweight and maintaining an unhealthy level of body fat into childbearing years. During pregnancy excess body fat is a risk factor for poor pregnancy outcomes and may predispose an infant to a lifelong heightened risk of being overweight and developing chronic disease. Interventions aimed at preventing the accumulation of body fat in adolescent girls and young women may have far reaching impact and be critically important in reducing intergenerational weight gain. Lifestyle interventions in adolescence have the potential to modify adult obesity risk by switching at-risk individuals from a high to lower obesity risk trajectory. This paper discusses multiple approaches to assist at-risk individuals reduce obesity risk. A key focus is placed on engagement in food preparation and choice, and opportunities for physical activity and sport. Support, education, and opportunity at home and at school, are often associated with the success of lifestyle interventions, and may enable adolescents to make positive choices, and engage in health promoting behaviors during adolescence and childbearing years.

  14. Alanine 310 is important for the activity of 1,4-α-glucan branching enzyme from Geobacillus thermoglucosidans STB02.

    PubMed

    Liu, Yiting; Li, Caiming; Gu, Zhengbiao; Xin, Chenhao; Cheng, Li; Hong, Yan; Li, Zhaofeng

    2017-04-01

    1,4-α-Glucan branching enzyme (GBE) catalyzes the formation of α-1,6 branch points in starch or glycogen by hydrolyzing α-1,4-glucosidic linkages and then synthesizing α-1,6-glucosidic linkages. In the GBE from Geobacillus thermoglucosidans STB02, alanine 310 (Ala310) is located in conserved region II. An analysis of the amino acid sequence shows that Ala310 is highly conserved in the prokaryotic GBE subfamily. Site-directed mutagenesis was used to determine the function of Ala310 in GBE. Replacement of Ala310 with glycine, aspartate, asparagine, isoleucine, glutamate, or glutamine resulted in mutant enzymes with less than 10% to 25% of wild-type activity when amylopectin or amylose was used as substrate. Studies using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) showed that A310G mutant had no effect on the transfer pattern, but the branching activity had been repressed to a large extent. Kinetic analysis also showed that mutations of Ala310 had an effect on the KM value that changed the preferred substrate from amylopectin to amylose. These results show that Ala310 is important for the catalytic activity of the GBE from G. thermoglucosidans STB02.

  15. Identification of residues important for the activity of Haloferax volcanii AglD, a component of the archaeal N-glycosylation pathway.

    PubMed

    Kaminski, Lina; Eichler, Jerry

    2010-05-06

    In Haloferax volcanii, AglD adds the final hexose to the N-linked pentasaccharide decorating the S-layer glycoprotein. Not knowing the natural substrate of the glycosyltransferase, together with the challenge of designing assays compatible with hypersalinity, has frustrated efforts at biochemical characterization of AglD activity. To circumvent these obstacles, an in vivo assay designed to identify amino acid residues important for AglD activity is described. In the assay, restoration of AglD function in an Hfx. volcanii aglD deletion strain transformed to express plasmid-encoded versions of AglD, generated through site-directed mutagenesis at positions encoding residues conserved in archaeal homologues of AglD, is reflected in the behavior of a readily detectable reporter of N-glycosylation. As such Asp110 and Asp112 were designated as elements of the DXD motif of AglD, a motif that interacts with metal cations associated with nucleotide-activated sugar donors, while Asp201 was predicted to be the catalytic base of the enzyme.

  16. Structural analysis of a penicillin V acylase from Pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity.

    PubMed

    Avinash, Vellore Sunder; Panigrahi, Priyabrata; Chand, Deepak; Pundle, Archana; Suresh, Cheravakattu Gopalan; Ramasamy, Sureshkumar

    2016-02-01

    Penicillin V acylases (PVA) catalyze the deacylation of the beta-lactam antibiotic phenoxymethylpenicillin (Pen V). They are members of the Ntn hydrolase family and possess an N-terminal cysteine as the main catalytic nucleophile residue. They form the evolutionarily related cholylglycine hydrolase (CGH) group which includes bile salt hydrolases (BSH) responsible for bile deconjugation. Even though a few PVA and BSH structures have been reported, no structure of a functional PVA from Gram-negative bacteria is available. Here, we report the crystal structure of a highly active PVA from Gram-negative Pectobacterium atrosepticum (PaPVA) at 2.5Å resolution. Structural comparison with PVAs from Gram-positive bacteria revealed that PaPVA had a distinctive tetrameric structure and active site organization. In addition, mutagenesis of key active site residues and biochemical characterization of the resultant variants elucidated the role of these residues in substrate binding and catalysis. The importance of residue Trp23 and Trp87 side chains in binding and correct positioning of Pen V by PVAs was confirmed using mutagenesis and substrate docking with a 15ns molecular dynamics simulation. These results establish the unique nature of Gram-negative CGHs and necessitate further research about their substrate spectrum.

  17. Overweight and Obese Adolescent Girls: The Importance of Promoting Sensible Eating and Activity Behaviors from the Start of the Adolescent Period

    PubMed Central

    Todd, Alwyn S.; Street, Steven J.; Ziviani, Jenny; Byrne, Nuala M.; Hills, Andrew P.

    2015-01-01

    The adolescent period is associated with changes in eating and activity behaviors in girls. Less reliance on parental provision and choice of food, coupled with a decrease in participation in physical activity and sport, can create an energy imbalance, predisposing to weight gain. Physiological alterations to body composition, reduction in insulin sensitivity, and psychological adjustments may further amplify the risk of becoming overweight and maintaining an unhealthy level of body fat into childbearing years. During pregnancy excess body fat is a risk factor for poor pregnancy outcomes and may predispose an infant to a lifelong heightened risk of being overweight and developing chronic disease. Interventions aimed at preventing the accumulation of body fat in adolescent girls and young women may have far reaching impact and be critically important in reducing intergenerational weight gain. Lifestyle interventions in adolescence have the potential to modify adult obesity risk by switching at-risk individuals from a high to lower obesity risk trajectory. This paper discusses multiple approaches to assist at-risk individuals reduce obesity risk. A key focus is placed on engagement in food preparation and choice, and opportunities for physical activity and sport. Support, education, and opportunity at home and at school, are often associated with the success of lifestyle interventions, and may enable adolescents to make positive choices, and engage in health promoting behaviors during adolescence and childbearing years. PMID:25690003

  18. Activation of the Nrf2 Cell Defense Pathway by Ancient Foods: Disease Prevention by Important Molecules and Microbes Lost from the Modern Western Diet.

    PubMed

    Senger, Donald R; Li, Dan; Jaminet, Shou-Ching; Cao, Shugeng

    2016-01-01

    The Nrf2 (NFE2L2) cell defense pathway protects against oxidative stress and disorders including cancer and neurodegeneration. Although activated modestly by oxidative stress alone, robust activation of the Nrf2 defense mechanism requires the additional presence of co-factors that facilitate electron exchange. Various molecules exhibit this co-factor function, including sulforaphane from cruciferous vegetables. However, natural co-factors that are potent and widely available from dietary sources have not been identified previously. The objectives of this study were to investigate support of the Nrf2 cell defense pathway by the alkyl catechols: 4-methylcatechol, 4-vinylcatechol, and 4-ethylcatechol. These small electrochemicals are naturally available from numerous sources but have not received attention. Findings reported here illustrate that these compounds are indeed potent co-factors for activation of the Nrf2 pathway both in vitro and in vivo. Each strongly supports expression of Nrf2 target genes in a variety of human cell types; and, in addition, 4-ethylcatechol is orally active in mice. Furthermore, findings reported here identify important and previously unrecognized sources of these compounds, arising from biotransformation of common plant compounds by lactobacilli that express phenolic acid decarboxylase. Thus, for example, Lactobacillus plantarum, Lactobacillus brevis, and Lactobacillus collinoides, which are consumed from a diet rich in traditionally fermented foods and beverages, convert common phenolic acids found in fruits and vegetables to 4-vinylcatechol and/or 4-ethylcatechol. In addition, all of the alkyl catechols are found in wood smoke that was used widely for food preservation. Thus, the potentially numerous sources of alkyl catechols in traditional foods suggest that these co-factors were common in ancient diets. However, with radical changes in food preservation, alkyl catechols have been lost from modern foods. The absence of alkyl

  19. Activation of the Nrf2 Cell Defense Pathway by Ancient Foods: Disease Prevention by Important Molecules and Microbes Lost from the Modern Western Diet

    PubMed Central

    Senger, Donald R.; Li, Dan; Jaminet, Shou-Ching; Cao, Shugeng

    2016-01-01

    The Nrf2 (NFE2L2) cell defense pathway protects against oxidative stress and disorders including cancer and neurodegeneration. Although activated modestly by oxidative stress alone, robust activation of the Nrf2 defense mechanism requires the additional presence of co-factors that facilitate electron exchange. Various molecules exhibit this co-factor function, including sulforaphane from cruciferous vegetables. However, natural co-factors that are potent and widely available from dietary sources have not been identified previously. The objectives of this study were to investigate support of the Nrf2 cell defense pathway by the alkyl catechols: 4-methylcatechol, 4-vinylcatechol, and 4-ethylcatechol. These small electrochemicals are naturally available from numerous sources but have not received attention. Findings reported here illustrate that these compounds are indeed potent co-factors for activation of the Nrf2 pathway both in vitro and in vivo. Each strongly supports expression of Nrf2 target genes in a variety of human cell types; and, in addition, 4-ethylcatechol is orally active in mice. Furthermore, findings reported here identify important and previously unrecognized sources of these compounds, arising from biotransformation of common plant compounds by lactobacilli that express phenolic acid decarboxylase. Thus, for example, Lactobacillus plantarum, Lactobacillus brevis, and Lactobacillus collinoides, which are consumed from a diet rich in traditionally fermented foods and beverages, convert common phenolic acids found in fruits and vegetables to 4-vinylcatechol and/or 4-ethylcatechol. In addition, all of the alkyl catechols are found in wood smoke that was used widely for food preservation. Thus, the potentially numerous sources of alkyl catechols in traditional foods suggest that these co-factors were common in ancient diets. However, with radical changes in food preservation, alkyl catechols have been lost from modern foods. The absence of alkyl

  20. Does Litter Impart A Detectable Chemical Signal on Soil DOC? DOC Fluorescence Signatures in Soils Undergoing Long-Term Litter Manipulations

    NASA Astrophysics Data System (ADS)

    Lajtha, K.; Strid, A.; Lee, B. S.

    2015-12-01

    Soil dissolved organic carbon (DOC) is a small but crucial part of the forest carbon cycle. Characterizing the relationship between organic matter inputs to soil and DOC chemistry is crucial to understanding the ultimate fate of root carbon, fallen wood and needles. Chemical differences in the DOC pool may help to explain whether fractions are sorbed to mineral surfaces and contribute to accumulation of soil organic carbon, respired as CO2, or exported. Soil solution DOC was sampled from the detrital input and removal treatment (DIRT) plots located in the H.J. Andrews Experimental Forest, OR to determine whether detrital inputs impart a detectable signal on DOC in mineral soil. Multiple types of fresh litter extracts, along with lysimeter and soil extracts from DIRT treatment plots were characterized using UV-Vis and fluorescence spectroscopy coupled with the Cory and McKnight (2005) parallel factor analysis (PARAFAC) model. Principal component analysis of 13 unique fluorophores distinguished using PARAFAC show that litter and soil extracts (needles, wood of decomposition Class 1, Class 3 and Class 5, O-horizon, and A-horizon) each have distinct fluorescence signatures. However, while litter-leached DOC chemistry varies by litter type, neither lysimeter-collected DOC or soil extracts show statistically significant differences in fluorescence signatures among treatments, even after 17 years of litter manipulations. The lack of observed differences among DIRT treatments suggests a "Soil Blender" hypothesis whereby both abiotic and biotic mechanisms effectively homogenize organic carbon constituents within the dissolved pool. The results of this work emphasize the ability of sorption and biodegradation to homogenize soil DOC and demonstrate that fluorescence can be an effective fingerprinting technique for soil DOC composition.

  1. A warning to the Brazilian Speech-Language Pathology and Audiology community about the importance of scientific and clinical activities in primary progressive aphasia.

    PubMed

    Beber, Bárbara Costa; Brandão, Lenisa; Chaves, Márcia Lorena Fagundes

    2015-01-01

    This article aims to warn the Brazilian Speech-Language Pathology and Audiology scientific community about the importance and necessity of scientific and clinical activities regarding Primary Progressive Aphasia. This warning is based on a systematic literature review of the scientific production on Primary Progressive Aphasia, from which nine Brazilian articles were selected. It was observed that there is an obvious lack of studies on the subject, as all the retrieved articles were published in medical journals and much of it consisted of small samples; only two articles described the effectiveness of speech-language therapy in patients with Primary Progressive Aphasia. A perspective for the future in the area and characteristics of Speech-Language Therapy for Primary Progressive Aphasia are discussed. As a conclusion, it is evident the need for greater action by Speech-Language Pathology and Audiology on Primary Progressive Aphasia.

  2. Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I).

    PubMed

    Vanhees, L; De Sutter, J; GeladaS, N; Doyle, F; Prescott, E; Cornelissen, V; Kouidi, E; Dugmore, D; Vanuzzo, D; Börjesson, M; Doherty, P

    2012-08-01

    Over the last decades, more and more evidence is accumulated that physical activity (PA) and exercise interventions are essential components in primary and secondary prevention for cardiovascular disease. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit in achieving cardiovascular health. The present paper, as the first of a series of three, will make specific recommendations on the importance of these characteristics for cardiovascular health in the population at large. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and the individual member of the public. Based on previous and the current literature, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and exercise.

  3. Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice.

    PubMed Central

    Wu-Hsieh, B A; Lee, G S; Franco, M; Hofman, F M

    1992-01-01

    Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection. Images PMID:1398934

  4. Importance of the type I insulin-like growth factor receptor in HER2, FGFR2 and MET-unamplified gastric cancer with and without Ras pathway activation

    PubMed Central

    Saisana, Marina; Griffin, S. Michael; May, Felicity E.B.

    2016-01-01

    Amplification of seven oncogenes: HER2, EGFR, FGFR1, FGFR2, MET, KRAS and IGF1R has been identified in gastric cancer. The first five are targeted therapeutically in patients with HER2-positivity, FGFR2- or MET-amplification but the majority of patients are triple-negative and require alternative strategies. Our aim was to evaluate the importance of the IGF1R tyrosine kinase in triple-negative gastric cancer with and without oncogenic KRAS, BRAF or PI3K3CA mutations. Cell lines and metastatic tumor cells isolated from patients expressed IGF1R, and insulin-like growth factor-1 (IGF-1) activated the PI3-kinase/Akt and Ras/Raf/MAP-kinase pathways. IGF-1 protected triple-negative cells from caspase-dependent apoptosis and anoikis. Protection was mediated via the PI3-kinase/Akt pathway. Remarkably, IGF-1-dependent cell survival was greater in patient samples. IGF-1 stimulated triple-negative gastric cancer cell growth was prevented by IGF1R knockdown and Ras/Raf/MAP-kinase pathway inhibition. The importance of the receptor in cell line and metastatic tumor cell growth in serum-containing medium was demonstrated by knockdown and pharmacological inhibition with figitumumab. The proportions of cells in S-phase and mitotic-phase, and Ras/Raf/MAP-kinase pathway activity, were reduced concomitantly. KRAS-addicted and BRAF-impaired gastric cancer cells were particularly susceptible. In conclusion, IGF1R and the IGF signal transduction pathway merit consideration as potential therapeutic targets in patients with triple-negative gastric cancer. PMID:27437872

  5. Validity, responsiveness, minimal detectable change, and minimal clinically important change of the Pediatric Motor Activity Log in children with cerebral palsy.

    PubMed

    Lin, Keh-chung; Chen, Hui-fang; Chen, Chia-ling; Wang, Tien-ni; Wu, Ching-yi; Hsieh, Yu-wei; Wu, Li-ling

    2012-01-01

    This study examined criterion-related validity and clinimetric properties of the Pediatric Motor Activity Log (PMAL) in children with cerebral palsy. Study participants were 41 children (age range: 28-113 months) and their parents. Criterion-related validity was evaluated by the associations between the PMAL and criterion measures at baseline and posttreatment, including the self-care, mobility, and cognition subscale, the total performance of the Functional Independence Measure in children (WeeFIM), and the grasping and visual-motor integration of the Peabody Developmental Motor Scales. Pearson correlation coefficients were calculated. Responsiveness was examined using the paired t test and the standardized response mean, the minimal detectable change was captured at the 90% confidence level, and the minimal clinically important change was estimated using anchor-based and distribution-based approaches. The PMAL-QOM showed fair concurrent validity at pretreatment and posttreatment and predictive validity, whereas the PMAL-AOU had fair concurrent validity at posttreatment only. The PMAL-AOU and PMAL-QOM were both markedly responsive to change after treatment. Improvement of at least 0.67 points on the PMAL-AOU and 0.66 points on the PMAL-QOM can be considered as a true change, not measurement error. A mean change has to exceed the range of 0.39-0.94 on the PMAL-AOU and the range of 0.38-0.74 on the PMAL-QOM to be regarded as clinically important change.

  6. Insecticidal, fumigant, and repellent activities of sweet wormwood oil and its individual components against red imported fire ant workers (Hymenoptera: Formicidae).

    PubMed

    Zhang, Ning; Tang, Liang; Hu, Wei; Wang, Kun; Zhou, You; Li, Hong; Huang, Congling; Chun, Jiong; Zhang, Zhixiang

    2014-01-01

    In total, 29 compounds from sweet wormwood (Artemisia annua L.) oil were identified using gas chromatography-mass spectrometry. The five active components were D-camphor, linalool, cineole, α-terpineol, and L(-)-borneol. The effectiveness of A. annua oil, as well as d-camphor, linalool, cineole, α-terpineol, and L(-)-borneol, as fumigants, contact insecticides, and repellents, were tested on the red imported fire ant Solenopsis invicta Buren. The results indicated that A. annua oil has no significant topical toxicity; however, the spray contact test revealed that it has strong insecticidal activity and the inhibitory effect is stronger during closed exposure than during open exposure. In the fumigant test, cineole and D-camphor exhibited strong fumigant toxicity on minor and major S. invicta workers. They also caused 100% mortality at 5, 3, 2, and 1 mg/centrifuge tube but not at 0.5 mg/centrifuge tube. The mortality rates of linalool, α-terpineol, and L(-)-borneol exceeded 80% at 5, 3, and 2 mg/centrifuge tube. In the repellent test, cineole and d-camphor showed significant repellency at 100, 10, and 1 mg/kg. However, linalool, α-terpineol, and L(-)-borneol significantly facilitated digging at 10 and 1 mg/kg.

  7. Low density lipoprotein receptor-binding activity in human tissues: Quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo

    SciTech Connect

    Rudling, M.J. Karolinska Institutet, Stockholm ); Reihner, E.; Einarsson, K.; Ewerth, S.; Angelin, B. )

    1990-05-01

    The heparin-sensitive binding of {sup 125}I-labeled low-density lipoprotein (LDL) to homogenates from 18 different normal human tissues and some solid tumors was determined. The binding to adrenal and liver homogenates fulfilled criteria established for the binding of LDL to its receptor--namely, (i) saturability, (ii) sensitivity to proteolytic destruction, (iii) inhibition by EDTA, and (iv) heat sensitivity. When the binding of {sup 125}I-labeled LDL was assayed at a constant concentration, the adrenal gland and the ovary had the highest binding of normal tissues. The highest binding per g of tissue overall was obtained in homogenates of a gastric carcinoma and a parotid adenoma. When the weights of the parenchymatous organs were considered, the major amount of LDL receptors was contained in the liver. To study the possible regulation of hepatic LDL-receptor expression, 11 patients were pretreated with cholestyramine. Increased binding activity was obtained in homogenates from liver biopsies from the cholestyramine-treated patients as compared with 12 untreated controls. It is concluded that the liver is the most important organ for LDL catabolism in humans and that the receptor activity in this organ can be regulated upon pharmacologic intervention. Further studies are needed to confirm the possibility that certain solid tumors can exhibit high numbers of LDL receptors.

  8. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion

    SciTech Connect

    Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R.

    2009-10-25

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.

  9. The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum: importance of active site metal ions in the binding of substrates and inhibitors.

    PubMed

    Maric, Selma; Donnelly, Sheila M; Robinson, Mark W; Skinner-Adams, Tina; Trenholme, Katharine R; Gardiner, Donald L; Dalton, John P; Stack, Colin M; Lowther, Jonathan

    2009-06-16

    The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development. This enzyme represents a target at which new antimalarials could be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo. A study on the metal ion binding characteristics of recombinant P. falciparum M17 leucine aminopeptidase (rPfLAP) shows that the active site of this exopeptidase contains two metal-binding sites, a readily exchangeable site (site 1) and a tight binding site (site 2). The enzyme retains activity when the metal ion is removed from site 1, while removal of metal ions from both sites results in an inactive apoenzyme that cannot be reactivated by the addition of divalent metal cations. The metal ion at site 1 is readily exchangeable with several divalent metal ions and displays a preference in the order of preference Zn(2+) > Mn(2+) > Co(2+) > Mg(2+). While it is likely that native PfLAP contains a Zn(2+) in site 2, the metal ion located in site 1 may be dependent on the type and concentration of metal ions in the cytosolic compartment of the parasite. Importantly, the type of metal ion present at site 1 influences not only the catalytic efficiency of the enzyme for peptide substrates but also the mode of binding by bestatin, a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity.

  10. The Rcs phosphorelay system is specific to enteric pathogens/commensals and activates ydeI, a gene important for persistent Salmonella infection of mice.

    PubMed

    Erickson, Kimberly D; Detweiler, Corrella S

    2006-11-01

    Bacteria utilize phosphorelay systems to respond to environmental or intracellular stimuli. Salmonella enterica encodes a four-step phosphorelay system that involves two sensor kinase proteins, RcsC and RcsD, and a response regulator, RcsB. The physiological stimulus for Rcs phosphorelay activation is unknown; however, Rcs-regulated genes can be induced in vitro by osmotic shock, low temperature and antimicrobial peptide exposure. In this report we investigate the role of the Rcs pathway using phylogenetic analysis and experimental techniques. Phylogenetic analysis determined that full-length RcsC- and RcsD-like proteins are generally restricted to Enterobacteriaceae species that have an enteric pathogenic or commensal relationship with the host. Experimental data show that RcsD and RcsB, in addition to RcsC, are important for systemic infection in mice and polymyxin B resistance in vitro. To identify Rcs-regulated genes that confer these phenotypes, we took advantage of our observation that RcsA, a transcription factor and binding partner of RcsB, is not required for polymyxin B resistance or survival in mice. S. enterica serovar Typhimurium oligonucleotide microarrays were used to identify 18 loci that are activated by RcsC, RcsD and RcsB but not RcsA. Five of the 18 loci encode genes that contribute to polymyxin B resistance. One of these genes, ydeI, was shown by quantitative real-time PCR to be regulated by the Rcs pathway independently of RcsA. Additionally, the stationary-phase sigma factor, RpoS (sigmaS), regulates ydeI transcription. In vivo infections show that ydeI mutants are out-competed by wild type 10- to 100-fold after oral inoculation, but are only modestly attenuated after intraperitoneal inoculation. These data indicate that ydeI is an Rcs-activated gene that plays an important role in persistent infection of mice, possibly by increasing bacterial resistance to antimicrobial peptides.

  11. Modeling of active transmembrane transport in a mixture theory framework.

    PubMed

    Ateshian, Gerard A; Morrison, Barclay; Hung, Clark T

    2010-05-01

    This study formulates governing equations for active transport across semi-permeable membranes within the framework of the theory of mixtures. In mixture theory, which models the interactions of any number of fluid and solid constituents, a supply term appears in the conservation of linear momentum to describe momentum exchanges among the constituents. In past applications, this momentum supply was used to model frictional interactions only, thereby describing passive transport processes. In this study, it is shown that active transport processes, which impart momentum to solutes or solvent, may also be incorporated in this term. By projecting the equation of conservation of linear momentum along the normal to the membrane, a jump condition is formulated for the mechano-electrochemical potential of fluid constituents which is generally applicable to nonequilibrium processes involving active transport. The resulting relations are simple and easy to use, and address an important need in the membrane transport literature.

  12. Energy imparted-based estimates of the effect of z overscanning on adult and pediatric patient effective doses from multi-slice computed tomography

    SciTech Connect

    Theocharopoulos, Nicholas; Damilakis, John; Perisinakis, Kostas; Gourtsoyiannis, Nicholas

    2007-04-15

    In the present study effective dose values normalized to computed tomography dose index measured free in air were calculated for adult, newborn, 1, 5, 10 and 15 year old patients regarding scans of the head, chest, abdomen, pelvis, abdomen and pelvis, and trunk, using the energy imparted method. The effect of z overscanning on patient doses was accounted for, and normalized doses are provided for varying beam collimation, pitch and reconstruction slice width values. The contribution of overscanning depends on patient age, anatomic region imaged, acquisition and reconstruction settings. For a head scan it constitutes 15% of the adult effective dose and 24% of the effective dose to a newborn but for an abdomen scan it may be as high as 58% for a newborn and 31% for an adult. The ratios of normalized pediatric doses relative to that for adults for helical scans depend not only on age but also on acquisition and reconstruction parameters, because of variations in the relative distance between the primary beam and the radiosensitive tissues/organs of the body. Regarding scans of the trunk, pediatric doses are up to a factor of 2.5 times higher compared to adult doses (abdominal scans), whereas for scans of the head up to a factor of 1.5. Increasing the pitch value of helical scans while maintaining the same effective mAs setting, and hence noise levels, leads to an increase in patient doses which depends on age, body region, scan and reconstruction parameters. The % difference between doses at pitch 1.5 and pitch 1 is more pronounced in the abdominal region (14% increase for adults) and in young patients (31% in a newborn and 18% in a 10 year old patient) and it is minimal in head scans (4% increase in newborns and 1% in adults). If multiple body regions are to be imaged, doses to adults can be reduced by up to 15% and 36% to children by performing single long-range scans. Scanning adult patients at 100 kVp instead of 120 kVp, results in a 32% reduction in effective

  13. The importance of earthquake-induced landslides to long-term slope erosion and slope-failure hazards in seismically active regions

    USGS Publications Warehouse

    Keefer, D.K.

    1994-01-01

    This paper describes a general method for determining the amount of earthquake-induced landsliding that occurs in a seismically active region over time; this determination can be used as a quantitative measure of the long-term hazard from seismically triggered landslides as well as a measure of the importance of this process to regional slope-erosion rates and landscape evolution. The method uses data from historical earthquakes to relate total volume of landslide material dislodged by an earthquake to the magnitude, M, and seismic moment, M0, of the earthquake. From worldwide data, a linear-regression relation between landslide volume, V, and M0 is determined as: V = M0/1018.9(?? 0.13), where V is measured in m3 and M0 is in dyn-cm. To determine the amount of earthquake-generated landsliding over time, this relation is combined with data on seismic-moment release for a particular region, which may be derived from either earthquake-history or fault-slip data. The form of the M0-V relation allows the rate of production of earthquake-induced landslides over time to be determined from total rate of seismic-moment release without regard to the distribution of individual events, thus simplifying and generalizing the determination. Application of the method to twelve seismically active regions, with areas ranging from 13,275 to 2,308,000 km2, shows that erosion rates from earthquake-induced landslides vary significantly from region to region. Of the regions studied, the highest rates were determined for the island of Hawaii, New Zealand, western New Guinea, and the San Francisco Bay region of California. Significantly lower rates were determined for Iran, Tibet, the Sierra Nevada-Great Basin region of California, and central Japan (for the time period from 715 AD to the present). Intermediate rates were determined for Peru, southern California, onshore California, Turkey, and central Japan (for the time period from 1586 AD to the present). To determine the relative, long

  14. Key Importance of Small RNA Binding for the Activity of a Glycine-Tryptophan (GW) Motif-containing Viral Suppressor of RNA Silencing*

    PubMed Central

    Pérez-Cañamás, Miryam; Hernández, Carmen

    2015-01-01

    Viruses express viral suppressors of RNA silencing (VSRs) to counteract RNA silencing-based host defenses. Although virtually all stages of the antiviral silencing pathway can be inhibited by VSRs, small RNAs (sRNAs) and Argonaute (AGO) proteins seem to be the most frequent targets. Recently, GW/WG motifs of some VSRs have been proposed to dictate their suppressor function by mediating interaction with AGO(s). Here we have studied the VSR encoded by Pelargonium line pattern virus (family Tombusviridae). The results show that p37, the viral coat protein, blocks RNA silencing. Site-directed mutagenesis of some p37 sequence traits, including a conserved GW motif, allowed generation of suppressor-competent and -incompetent molecules and uncoupling of the VSR and particle assembly capacities. The engineered mutants were used to assess the importance of p37 functions for viral infection and the relative contribution of diverse molecular interactions to suppressor activity. Two main conclusions can be drawn: (i) the silencing suppression and encapsidation functions of p37 are both required for systemic Pelargonium line pattern virus infection, and (ii) the suppressor activity of p37 relies on the ability to bind sRNAs rather than on interaction with AGOs. The data also caution against potential misinterpretations of results due to overlap of sequence signals related to distinct protein properties. This is well illustrated by mutation of the GW motif in p37 that concurrently affects nucleolar localization, efficient interaction with AGO1, and sRNA binding capability. These concomitant effects could have been overlooked in other GW motif-containing suppressors, as we exemplify with the orthologous p38 of turnip crinkle virus. PMID:25505185

  15. In vitro antibacterial activity of sphaeropsidins and chemical derivatives toward Xanthomonas oryzae pv. oryzae, the causal agent of rice bacterial blight.

    PubMed

    Evidente, Antonio; Venturi, Vittorio; Masi, Marco; Degrassi, Giuliano; Cimmino, Alessio; Maddau, Lucia; Andolfi, Anna

    2011-12-27

    Sphaeropsidin A, the main phytotoxin produced by Diplodia cupressi, as well as the two natural analogues sphaeropsidins B and C and 14 derivatives obtained by chemical modifications were assayed for antibacterial activity against Xanthomonas oryzae pv. oryzae, Pseudomonas fuscovaginae, and Burkholderia glumae, the causal agents of severe bacterial rice diseases. The results showed a strong and specific activity of sphaeropsidin A against X. oryzae pv. oryzae, while no activity was observed against the other two pathogens. The results of structure-activity relationship studies showed that structural features important to impart this antibacterial activity are the presence of the C-7 carbonyl group and the hemiketalic lactone functionality. The C-13 vinyl group, the double bond of ring C, and/or the tertiary C-9 hydroxy group, as well as the pimarane arrangement of the tricylic carbon skeleton, were also important for the antibacterial activity. These findings may be useful in designing novel compounds for practical applications in agriculture.

  16. A new serotonin 5-HT6 receptor antagonist with procognitive activityImportance of a halogen bond interaction to stabilize the binding

    NASA Astrophysics Data System (ADS)

    González-Vera, Juan A.; Medina, Rocío A.; Martín-Fontecha, Mar; Gonzalez, Angel; de La Fuente, Tania; Vázquez-Villa, Henar; García-Cárceles, Javier; Botta, Joaquín; McCormick, Peter J.; Benhamú, Bellinda; Pardo, Leonardo; López-Rodríguez, María L.

    2017-01-01

    Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer’s disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit.

  17. A new serotonin 5-HT6 receptor antagonist with procognitive activityImportance of a halogen bond interaction to stabilize the binding

    PubMed Central

    González-Vera, Juan A.; Medina, Rocío A.; Martín-Fontecha, Mar; Gonzalez, Angel; de la Fuente, Tania; Vázquez-Villa, Henar; García-Cárceles, Javier; Botta, Joaquín; McCormick, Peter J.; Benhamú, Bellinda; Pardo, Leonardo; López-Rodríguez, María L.

    2017-01-01

    Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer’s disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit. PMID:28117458

  18. Characterization of a Novel Integrin Binding Protein, VPS33B, Which is Important for Platelet Activation and in vivo Thrombosis and Hemostasis

    PubMed Central

    Xiang, Binggang; Zhang, Guoying; Ye, Shaojing; Zhang, Rui; Huang, Cai; Liu, Jun; Tao, Min; Ruan, Changgeng; Smyth, Susan S.; Whiteheart, Sidney W.; Li, Zhenyu

    2015-01-01

    Background Integrins are heterodimeric (α/β) membrane proteins that play fundamental roles in many biological processes, e.g. cell adhesion and spreading, which are important for platelet function and hemostasis. The molecular mechanism that regulates integrin activation is not completely understood. Methods and Results Here, we show that VPS33B, a member of the Sec1/Munc18 (SM) family and a component of the Vps-C tethering complexes, binds directly to the integrin β subunit. Overexpression of VPS33B in CHO cells potentiated αIIbβ3 outside-in signaling but not inside-out signaling. Platelets, from megakaryocyte- and platelet-specific VPS33B conditional knockout mice, had normal morphology yet their spreading on fibrinogen was impaired and they failed to support clot retraction. Platelet aggregation and ATP secretion in response to low-dose agonists were reduced in the VPS33B knockout mice. αIIbβ3-mediated endocytosis of fibrinogen was also defective. Tail bleeding times and times to occlusion in a FeCl3-induced thrombosis model were prolonged in the VPS33B knockout mice. Furthermore, VPS33B acted upstream of the RhoA-ROCK-MLC and Rac1 dependent pathways that lead to clot retraction and cell spreading, respectively. Conclusions Our work demonstrates that vesicular trafficking complexes, containing VPS33B, are a novel class of modifiers of integrin function. Our data also provide insights into the molecular mechanism and treatment of ARC syndrome. PMID:26399659

  19. A new serotonin 5-HT6 receptor antagonist with procognitive activity - Importance of a halogen bond interaction to stabilize the binding.

    PubMed

    González-Vera, Juan A; Medina, Rocío A; Martín-Fontecha, Mar; Gonzalez, Angel; de la Fuente, Tania; Vázquez-Villa, Henar; García-Cárceles, Javier; Botta, Joaquín; McCormick, Peter J; Benhamú, Bellinda; Pardo, Leonardo; López-Rodríguez, María L

    2017-01-24

    Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer's disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit.

  20. Aspergillus niger lipase: Heterologous expression in Pichia pastoris, molecular modeling prediction and the importance of the hinge domains at both sides of the lid domain to interfacial activation.

    PubMed

    Shu, Zhengyu; Duan, Mojie; Yang, Jiangke; Xu, Li; Yan, Yunjun

    2009-01-01

    Aspergillus niger lipase (ANL) is an important biocatalyst in the food processing industry. However, there is no report of its detailed three-dimensional structure because of difficulties in crystallization. In this article, based on experimental data and bioinformational analysis results, the structural features of ANL were simulated. Firstly, two recombinant ANLs expressed in Pichia pastoris were purified to homogeneity and their corresponding secondary structure compositions were determined by circular dichroism spectra. Secondly, the primary structure, the secondary structure and the three-dimensional structure of ANL were modeled by comparison with homologous lipases with known three-dimensional structures using the BioEdit software, lipase engineering database (http://www.led.uni-stuttgart.de/), PSIPRED server and SwissModel server. The predicted molecular structure of ANL presented typical features of the alpha/beta hydrolase fold including positioning of the putative catalytic triad residues and the GXSXG signature motif. Comparison of the predicted three-dimensional structure of ANL with the X-ray three-dimensional structure of A. niger feruloyl esterase showed that the functional difference of interfacial activation between lipase and esterase was concerned with the difference in position of the lid. Our three-dimensional model of ANL helps to modify lipase structure by protein engineering, which will further expand the scope of application of ANL.

  1. Effect of the permafrost thawing on the organic carbon and microbial activity in thermokarst lakes of Western Siberia: important source of carbon dioxide in the atmosphere

    NASA Astrophysics Data System (ADS)

    Shirokova, L. S.; Pokrovsky, O. S.; Kirpotin, S. N.; Dupre, B.

    2008-12-01

    "khasyrei" exhibits the highest pH (5.5-6.0), presence of green algae and plants, very low conductivity (4-9 μS) and the lowest OC concentrations. However, there is still quite weak primary productivity (˜ 0.01 mg/C/L) and significant mineralization rate (0.3 mg C/L/day). The bacterial biomass and the number of colony-forming units for different nutrient media demonstrate clear decrease with the temporal evolution of the lake from dystrophic (7000 CFU/mL) at the begging of permafrost thawing to oligotrophic/mesotrophic at the final "khasyrey" stage (80 CFU/mL). Two main conclusions can be drawn from this work: 1) At all stages of lake evolution, there is always high amount of active OM-mineralizing heterotrophic bacteria, and 2) mineralization processes by these microorganisms clearly dominate any possible CO2 consumption by the phytoplankton. As a result, Western Siberia thermokarstic lakes are likely to act as important source of CO2 to the atmosphere. The CO2 flux associated with this microbial activity (i.e., 400 +/- 200 t/km2/y, assuming average lake depth of 1 m) is at least one order of magnitude higher than the riverine DOC flux, bearing in mind very high proportion of newly formed lakes in the Western Siberia (up to 30 percent).

  2. Functional constraints on SoxE proteins in neural crest development: The importance of differential expression for evolution of protein activity.

    PubMed

    Lee, Eric M; Yuan, Tian; Ballim, Reyna D; Nguyen, Kristy; Kelsh, Robert N; Medeiros, Daniel M; McCauley, David W

    2016-10-01

    duplicates, but such specialization does not appear to have occurred in gnathostomes. This highlights an important difference in the evolution of SoxE activity between these two divergent vertebrate lineages and provides insights for understanding how cell fate restriction in different NCC populations may be dependent on subfunctionalization among SoxE duplicates.

  3. Evidence for an active T-state pig kidney fructose 1,6-bisphosphatase: interface residue Lys-42 is important for allosteric inhibition and AMP cooperativity.

    PubMed Central

    Lu, G.; Stec, B.; Giroux, E. L.; Kantrowitz, E. R.

    1996-01-01

    During the R-->T transition in the tetrameric pig kidney fructose-1,6-bisphosphatase (Fru-1,6-P2ase, EC 3.1.3.11) a major change in the quaternary structure of the enzyme occurs that is induced by the binding of the allosteric inhibitor AMP (Ke HM, Liang JY, Zhang Y, Lipscomb WN, 1991, Biochemistry 30:4412-4420). The change in quaternary structure involving the rotation of the upper dimer by 17 degrees relative to the lower dimer is coupled to a series of structural changes on the secondary and tertiary levels. The structural data indicate that Lys-42 is involved in a complex set of intersubunit interactions across the dimer-dimer interface with residues of the 190's loop, a loop located at the pivot of the allosteric rotation. In order to test the function of Lys-42, we have replaced it with alanine using site-specific mutagenesis. The kcat and K(m) values for Lys-42-->Ala Fru-1,6-P2ase were 11 s-1 and 3.3 microM, respectively, resulting in a mutant enzyme that was slightly less efficient catalytically than the normal pig kidney enzyme. Although the Lys-42-->Ala Fru-1,6-P2ase was similar kinetically in terms of K(m) and kcat, the response to inhibition by AMP was significantly different than that of the normal pig kidney enzyme. Not only was AMP inhibition no longer cooperative, but also it occurred in two stages, corresponding to high- and low-affinity binding sites. Saturation of the high-affinity sites only reduced the activity by 30%, compared to 100% for the wild-type enzyme. In order to determine in what structural state the enzyme was after saturation of the high-affinity sites, the Lys-42-->Ala enzyme was crystallized in the presence of Mn2+, fructose-6-phosphate (Fru-6-P), and 100 microM AMP and the data collected to 2.3 A resolution. The X-ray structure showed the T state with AMP binding with full occupancy to the four regulatory sites and the inhibitor Fru-6-P bound at the active sites. The results reported here suggest that, in the normal pig kidney

  4. Importance of the short cytoplasmic domain of the feline immunodeficiency virus transmembrane glycoprotein for fusion activity and envelope glycoprotein incorporation into virions

    SciTech Connect

    Celma, Cristina C.P.; Paladino, Monica G.; Gonzalez, Silvia A.; Affranchino, Jose L.

    2007-09-30

    The mature form of the envelope (Env) glycoprotein of lentiviruses is a heterodimer composed of the surface (SU) and transmembrane (TM) subunits. Feline immunodeficiency virus (FIV) possesses a TM glycoprotein with a cytoplasmic tail of approximately 53 amino acids which is unusually short compared with that of the other lentiviral glycoproteins (more than 100 residues). To investigate the relevance of the FIV TM cytoplasmic domain to Env-mediated viral functions, we characterized the biological properties of a series of Env glycoproteins progressively shortened from the carboxyl terminus. All the mutant Env proteins were efficiently expressed in feline cells and processed into the SU and TM subunits. Deletion of 5 or 11 amino acids from the TM C-terminus did not significantly affect Env surface expression, fusogenic activity or Env incorporation into virions, whereas removal of 17 or 23 residues impaired Env-mediated cell-to-cell fusion. Further truncation of the FIV TM by 29 residues resulted in an Env glycoprotein that was poorly expressed at the cell surface, exhibited only 20% of the wild-type Env fusogenic capacity and was inefficiently incorporated into virions. Remarkably, deletion of the TM C-terminal 35 or 41 amino acids restored or even enhanced Env biological functions. Indeed, these mutant Env glycoproteins bearing cytoplasmic domains of 18 or 12 amino acids were found to be significantly more fusogenic than the wild-type Env and were efficiently incorporated into virions. Interestingly, truncation of the TM cytoplasmic domain to only 6 amino acids did not affect Env incorporation into virions but abrogated Env fusogenicity. Finally, removal of the entire TM cytoplasmic tail or deletion of as many as 6 amino acids into the membrane-spanning domain led to a complete loss of Env functions. Our results demonstrate that despite its relatively short length, the FIV TM cytoplasmic domain plays an important role in modulating Env-mediated viral functions.

  5. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    PubMed

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-05-13

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

  6. Antimicrobial peptides: a review of how peptide structure impacts antimicrobial activity

    NASA Astrophysics Data System (ADS)

    Soares, Jason W.; Mello, Charlene M.

    2004-03-01

    Antimicrobial peptides (AMPs) have been discovered in insects, mammals, reptiles, and plants to protect against microbial infection. Many of these peptides have been isolated and studied exhaustively to decipher the molecular mechanisms that impart protection against infectious bacteria, fungi, and viruses. Unfortunately, the molecular mechanisms are still being debated within the scientific community but valuable clues have been obtained through structure/function relationship studies1. Biophysical studies have revealed that cecropins, isolated from insects and pigs, exhibit random structure in solution but undergo a conformational change to an amphipathic α-helix upon interaction with a membrane surface2. The lack of secondary structure in solution results in an extremely durable peptide able to survive exposure to high temperatures, organic solvents and incorporation into fibers and films without compromising antibacterial activity. Studies to better understand the antimicrobial action of cecropins and other AMPs have provided insight into the importance of peptide sequence and structure in antimicrobial activities. Therefore, enhancing our knowledge of how peptide structure imparts function may result in customized peptide sequences tailored for specific applications such as targeted cell delivery systems, novel antibiotics and food preservation additives. This review will summarize the current state of knowledge with respect to cell binding and antimicrobial activity of AMPs focusing primarily upon cecropins.

  7. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III).

    PubMed

    Vanhees, L; Rauch, B; Piepoli, M; van Buuren, F; Takken, T; Börjesson, M; Bjarnason-Wehrens, B; Doherty, P; Dugmore, D; Halle, M

    2012-12-01

    The beneficial effect of exercise training and exercise-based cardiac rehabilitation on symptom-free exercise capacity,cardiovascular and skeletal muscle function, quality of life, general healthy lifestyle, and reduction of depressive symptoms and psychosocial stress is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity (PA) and exercise training--frequency, intensity, time (duration), type (mode), and volume (dose: intensity x duration) of exercise--are the most effective. The present paper, therefore, will deal with these exercise characteristics in the management of individuals with cardiovascular disease, i.e. coronary artery disease and chronic heart failure patients, but also in patients with congenital or valvular heart disease. Based on the current literature, and if sufficient evidence is available, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding frequency, intensity, time and type of PA, and safety aspects during exercise inpatients with cardiovascular disease. This paper is the third in a series of three papers, all devoted to the same theme: the importance of the exercise characteristics in the management of cardiovascular health. Part I is directed to the general population and Part II to individuals with cardiovascular risk factors. In general, PA recommendations and exercise training programmes for patients with coronary artery disease or chronic heart failure need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible and to perform endurance exercise training 30–60 min daily (3–5 days per week) in combination with resistance training 2–3 times a week. Because of the frequently reported dose–response relationship between training effect and exercise intensity, one should seek sufficiently high training intensities

  8. DNA Import into Mitochondria.

    PubMed

    Konstantinov, Yu M; Dietrich, A; Weber-Lotfi, F; Ibrahim, N; Klimenko, E S; Tarasenko, V I; Bolotova, T A; Koulintchenko, M V

    2016-10-01

    In recent decades, it has become evident that the condition for normal functioning of mitochondria in higher eukaryotes is the presence of membrane transport systems of macromolecules (proteins and nucleic acids). Natural competence of the mitochondria in plants, animals, and yeasts to actively uptake DNA may be directly related to horizontal gene transfer into these organelles occurring at much higher rate compared to the nuclear and chloroplast genomes. However, in contrast with import of proteins and tRNAs, little is known about the biological role and molecular mechanism underlying import of DNA into eukaryotic mitochondria. In this review, we discuss current state of investigations in this area, particularly specificity of DNA import into mitochondria and its features in plants, animals, and yeasts; a tentative mechanism of DNA import across the mitochondrial outer and inner membranes; experimental data evidencing several existing, but not yet fully understood mechanisms of DNA transfer into mitochondria. Currently available data regarding transport of informational macromolecules (DNA, RNA, and proteins) into the mitochondria do not rule out that the mechanism of protein and tRNA import as well as tRNA and DNA import into the mitochondria may partially overlap.

  9. The association between telomerase activity and expression of its RNA component (hTR) in breast cancer patients: the importance of DNase treatment

    PubMed Central

    Hosseini-Asl, Saied; Modarressi, Mohammad H; Atri, Morteza; Salhab, Mohamed; Mokbel, Kefah; Mehdipour, Parvin

    2006-01-01

    Telomerase is a ribonucleoprotein enzyme that compensates for the telomere length shortening which occurs during the cell cycle. Telomerase activity has been detected in most tumours but not in somatic cells. However, hTR; the RNA component of telomerase; has been reported to be universally expressed in both cancerous and non-cancerous tissues. Tumour samples from 50 patients with primary invasive breast cancer were collected. The TRAP assay was used to detect telomerase activity. RT-PCR on cDNA and DNased cDNA samples and control groups was used to detect the expression of hTR, GAPDH and PGM1 genes. Seventy-two percent of samples showed telomerase activity. DNA contamination was detected in 36 (72%) of RNA samples. Without performing DNase treatment, 49 (98%) of all samples showed hTR expression, but with the application of this strategy, hTR expression decreased from 98% to 64%. A significant association (p < 0.001) between hTR expression and telomerase activity was observed. Among the 32 hTR positive samples, 30 had telomerase activity and among the 18 hTR negative samples, telomerase activity was observed in 6 cases. Thus the application of this strategy could provide an applicable tool to use instead of the TRAP assay thus facilitating telomerase research in cancer genetic investigations. PMID:16749934

  10. The association between telomerase activity and expression of its RNA component (hTR) in breast cancer patients: the importance of DNase treatment.

    PubMed

    Hosseini-Asl, Saied; Modarressi, Mohammad H; Atri, Morteza; Salhab, Mohamed; Mokbel, Kefah; Mehdipour, Parvin

    2006-06-02

    Telomerase is a ribonucleoprotein enzyme that compensates for the telomere length shortening which occurs during the cell cycle. Telomerase activity has been detected in most tumours but not in somatic cells. However, hTR; the RNA component of telomerase; has been reported to be universally expressed in both cancerous and non-cancerous tissues. Tumour samples from 50 patients with primary invasive breast cancer were collected. The TRAP assay was used to detect telomerase activity. RT-PCR on cDNA and DNased cDNA samples and control groups was used to detect the expression of hTR, GAPDH and PGM1 genes. Seventy-two percent of samples showed telomerase activity. DNA contamination was detected in 36 (72%) of RNA samples. Without performing DNase treatment, 49 (98%) of all samples showed hTR expression, but with the application of this strategy, hTR expression decreased from 98% to 64%. A significant association (p < 0.001) between hTR expression and telomerase activity was observed. Among the 32 hTR positive samples, 30 had telomerase activity and among the 18 hTR negative samples, telomerase activity was observed in 6 cases. Thus the application of this strategy could provide an applicable tool to use instead of the TRAP assay thus facilitating telomerase research in cancer genetic investigations.

  11. Nuclear Import of JAK1 Is Mediated by a Classical NLS and Is Required for Survival of Diffuse Large B-cell Lymphoma.

    PubMed

    Zhu, Fen; Hwang, Byounghoon; Miyamoto, Shigeki; Rui, Lixin

    2017-03-01

    JAKs are non-receptor tyrosine kinases that are generally found in association with cytokine receptors. In the canonical pathway, roles of JAKs have well been established in activating STATs in response to cytokine stimulation to modulate gene transcription. In contrast, a noncanonical role of JAK2 has recently been discovered, in which JAK2 in the nucleus imparts the epigenetic regulation of gene transcription through phosphorylation of tyrosine 41 on the histone protein H3. Recent work further demonstrated that this noncanonical mechanism is conserved with JAK1, which is activated by the autocrine cytokines IL6 and IL10 in activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL), a cancer type that is particularly difficult to treat and has poor prognosis. However, how JAK1 gains access to the nucleus to enable epigenetic regulation remains undefined. Here, we investigated this question and revealed that JAK1 has a classical nuclear localization signal toward the N-terminal region, which can be recognized by multiple importin α isoforms. Moreover, the nuclear import of JAK1 is independent of its kinase activity but is required for the optimal expansion of ABC DLBCL cells in vitroImplications: This study demonstrates that the nuclear import of JAK1 is essential for the optimal fitness of ABC DLBCL cells, and targeting JAK1 nuclear localization is a potential therapeutic strategy for ABC DLBCL. Mol Cancer Res; 15(3); 348-57. ©2016 AACR.

  12. Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge

    NASA Astrophysics Data System (ADS)

    Liu, R. L.; Hurley, M. F.; Kvryan, A.; Williams, G.; Scully, J. R.; Birbilis, N.

    2016-06-01

    The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

  13. Controlling the corrosion and cathodic activation of magnesium via microalloying additions of Ge.

    PubMed

    Liu, R L; Hurley, M F; Kvryan, A; Williams, G; Scully, J R; Birbilis, N

    2016-06-28

    The evolution of corrosion morphology and kinetics for magnesium (Mg) have been demonstrated to be influenced by cathodic activation, which implies that the rate of the cathodic partial reaction is enhanced as a result of anodic dissolution. This phenomenon was recently demonstrated to be moderated by the use of arsenic (As) alloying as a poison for the cathodic reaction, leading to significantly improved corrosion resistance. The pursuit of alternatives to toxic As is important as a means to imparting a technologically safe and effective corrosion control method for Mg (and its alloys). In this work, Mg was microalloyed with germanium (Ge), with the aim of improving corrosion resistance by retarding cathodic activation. Based on a combined analysis herein, we report that Ge is potent in supressing the cathodic hydrogen evolution reaction (reduction of water) upon Mg, improving corrosion resistance. With the addition of Ge, cathodic activation of Mg subject to cyclic polarisation was also hindered, with beneficial implications for future Mg electrodes.

  14. The chemical activity of metal compound nanoparticles: Importance of electronic and steric effects in M8C12 (M=Ti, V, Mo) metcars

    NASA Astrophysics Data System (ADS)

    Liu, Ping; Rodriguez, José A.; Muckerman, James T.

    2004-12-01

    Density functional theory was employed to investigate the chemical activity of metal carbide nanoparticles. The present calculations indicate that M8C12 (M=Ti, V, Mo) nanoparticles exhibit a unique behavior compared to metal [M(001)] and metal carbide surfaces [M2C(001) and MC(001)]. It is found that the nanoparticles behave very reactive in spite of the high carbon concentration in some reactions, while surprisingly inert in other cases. Our study reveals that the unexpected activity is the result of the interplay of shifts in the metal d-bands and distortions in the geometry of the metal carbide nanoparticles.

  15. Diet and gender are important factors modulating low frequency EEG activity during processing of language sounds in 3 month old infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about how early postnatal diet affects brain processes related to cognitive function in healthy infants. To address this question we examined EEG activity recorded from 3 month old infants [breastfed (BF: n = 104, 55 males), milk-based formula fed (MF: n = 114, 57 males) or soy for...

  16. Isolation of CA1 nuclear enriched fractions from hippocampal slices to study activity-dependent nuclear import of synapto-nuclear messenger proteins.

    PubMed

    Yuanxiang, Pingan; Bera, Sujoy; Karpova, Anna; Kreutz, Michael R; Mikhaylova, Marina

    2014-08-10

    Studying activity dependent protein expression, subcellular translocation, or phosphorylation is essential to understand the underlying cellular mechanisms of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) induced in acute hippocampal slices are widely accepted as cellular models of learning and memory. There are numerous studies that use live cell imaging or immunohistochemistry approaches to visualize activity dependent protein dynamics. However these methods rely on the suitability of antibodies for immunocytochemistry or overexpression of fluorescence-tagged proteins in single neurons. Immunoblotting of proteins is an alternative method providing independent confirmation of the findings. The first limiting factor in preparation of subcellular fractions from individual tetanized hippocampal slices is the low amount of material. Second, the handling procedure is crucial because even very short and minor manipulations of living slices might induce activation of certain signaling cascades. Here we describe an optimized workflow in order to obtain sufficient quantity of nuclear enriched fraction of sufficient purity from the CA1 region of acute hippocampal slices from rat brain. As a representative example we show that the ERK1/2 phosphorylated form of the synapto-nuclear protein messenger Jacob actively translocates to the nucleus upon induction of LTP and can be detected in a nuclear enriched fraction from CA1 neurons.

  17. Hydrogenation of CO2 to methanol: Importance of metal–oxide and metal–carbide interfaces in the activation of CO2

    DOE PAGES

    Rodriguez, José A.; Liu, Ping; Stacchiola, Dario J.; ...

    2015-09-30

    In this study, the high thermochemical stability of CO2 makes it very difficult to achieve the catalytic conversion of the molecule into alcohols or other hydrocarbon compounds, which can be used as fuels or the starting point for the generation of fine chemicals. Pure metals and bimetallic systems used for the CO2 → CH3OH conversion usually bind CO2 too weakly and, thus, show low catalytic activity. Here, we discuss a series of recent studies that illustrate the advantages of metal–oxide and metal–carbide interfaces when aiming at the conversion of CO2 into methanol. CeOx/Cu(111), Cu/CeOx/TiO2(110), and Au/CeOx/TiO2(110) exhibit an activity formore » the CO2 → CH3OH conversion that is 2–3 orders of magnitude higher than that of a benchmark Cu(111) catalyst. In the Cu–ceria and Au–ceria interfaces, the multifunctional combination of metal and oxide centers leads to complementary chemical properties that open active reaction pathways for methanol synthesis. Efficient catalysts are also generated after depositing Cu and Au on TiC(001). In these cases, strong metal–support interactions modify the electronic properties of the admetals and make them active for the binding of CO2 and its subsequent transformation into CH3OH at the metal–carbide interfaces.« less

  18. Validity, Responsiveness, Minimal Detectable Change, and Minimal Clinically Important Change of the Pediatric Motor Activity Log in Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Lin, Keh-chung; Chen, Hui-fang; Chen, Chia-ling; Wang, Tien-ni; Wu, Ching-yi; Hsieh, Yu-wei; Wu, Li-ling

    2012-01-01

    This study examined criterion-related validity and clinimetric properties of the Pediatric Motor Activity Log (PMAL) in children with cerebral palsy. Study participants were 41 children (age range: 28-113 months) and their parents. Criterion-related validity was evaluated by the associations between the PMAL and criterion measures at baseline and…

  19. Accelerometer measured daily physical activity and sedentary pursuits–comparison between two models of the Actigraph and the importance of data reduction

    PubMed Central

    2013-01-01

    Background Very few validation studies have been performed between different generations of the commonly used Actigraph accelerometers. We compared daily physical activity data generated from the old generation Actigraph model 7164 with the new generation Actigraph GT1M accelerometer in 15 young females for eight consecutive days. We also investigated if different wear time thresholds had any impact on the findings. Minutes per day of moderate and vigorous physical activity (MVPA), vigorous physical activity (VPA) and very vigorous physical activity (VVPA) were calculated. Moreover, minutes of sedentary pursuits per day were calculated. Findings There were significant (P < 0.05) differences between the Actigraph 7164 and the GT1M concerning MVPA (61 ± 21vs. 56 ± 23 min/day), VPA (12 ± 8 vs. 9 ± 3 min/day) and VVPA (3.2 ± 3.0 vs. 0.3 ± 1.1 min/day). The different wear time thresholds had little impact on minutes per day in different intensities. Median minutes of sedentary pursuits per day ranged from 159 to 438 minutes depending on which wear time threshold was used (i.e. 10, 30 or 60 minutes), whereas very small differences were observed between the two different models. Conclusions Data from the old generation Actigraph 7164 and the new generation Actigraph GT1M accelerometers differ, where the Actigraph GT1M generates lower minutes spent in free living physical activity. Median minutes of sedentary pursuits per day are highly dependent on which wear time threshold that is used, and not by accelerometer model. PMID:24176143

  20. Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors.

    PubMed

    Gallagher, Ferdia A; Sladen, Helen; Kettunen, Mikko I; Serrao, Eva M; Rodrigues, Tiago B; Wright, Alan; Gill, Andrew B; McGuire, Sarah; Booth, Thomas C; Boren, Joan; McIntyre, Alan; Miller, Jodi L; Lee, Shen-Han; Honess, Davina; Day, Sam E; Hu, De-En; Howat, William J; Harris, Adrian L; Brindle, Kevin M

    2015-10-01

    Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH.

  1. Carbonic anhydrase activity monitored in vivo by hyperpolarized 13C-magnetic resonance spectroscopy demonstrate its importance for pH regulation in tumors

    PubMed Central

    Gallagher, Ferdia A.; Sladen, Helen; Kettunen, Mikko I.; Serrao, Eva M.; Rodrigues, Tiago B.; Wright, Alan; Gill, Andrew B.; McGuire, Sarah; Booth, Thomas C.; Boren, Joan; McIntyre, Alan; Miller, Jodi L.; Lee, Shen-Han; Honess, Davina; Day, Sam E.; Hu, De-en; Howat, William J.; Harris, Adrian L.; Brindle, Kevin M.

    2015-01-01

    Carbonic anhydrase (CA) buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3−). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized 13C label between bicarbonate (H13CO3−) and carbon dioxide (13CO2), following injection of hyperpolarized H13CO3−, using 13C magnetic resonance spectroscopy (13C-MRS) magnetization transfer measurements. 31P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and 13C-MRS measurements of the H13CO3−/13CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the 13C measurements overestimated pH due to incomplete equilibration of the hyperpolarized 13C label between the H13CO3− and 13CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevates tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH, and supports the hypothesis that a major function of CAIX is to lower the extracellular pH. PMID:26249175

  2. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    PubMed

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters.

  3. Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4.

    PubMed

    Reilly, B D; Levine, R P; Skanes, V M

    1991-11-01

    The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e., Pro, Cys, Pro, Val, Leu, Asp in C4A and Leu, Ser, Pro, Val Ile, His in C4B. These residues may be responsible either in part or entirely for properties associated with isotype. To examine the functional role of residues 1101-1106 in C4B-mediated hemolysis, whole serum or immunopurified human C4 with allotypes, A3B1, A3, B2B1, or B1 were preincubated in the presence or absence of an antipeptide mAb (BII-1) specific for amino acid residues 1101-1105 of C4B. Sensitized sheep E and C4-deficient guinea pig serum was then added and lysis measured by absorbance at 415 nm. Our results show lysis of antibody-sensitized sheep E is inhibited by antibody and C4B2B1, C4B1, or C4A3B1 but not antibody and C4A3. The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity. Furthermore, results from uptake experiments show that BII-1 interferes with the covalent binding activity of C4B, indicating residues 1101-1105 play a role in the covalent binding reaction of C4B to the target E-antibody complex.

  4. Hydrogenation of CO2 to methanol: Importance of metal–oxide and metal–carbide interfaces in the activation of CO2

    SciTech Connect

    Rodriguez, José A.; Liu, Ping; Stacchiola, Dario J.; Senanayake, Sanjaya D.; White, Michael G.; Chen, Jingguang G.

    2015-09-30

    In this study, the high thermochemical stability of CO2 makes it very difficult to achieve the catalytic conversion of the molecule into alcohols or other hydrocarbon compounds, which can be used as fuels or the starting point for the generation of fine chemicals. Pure metals and bimetallic systems used for the CO2 → CH3OH conversion usually bind CO2 too weakly and, thus, show low catalytic activity. Here, we discuss a series of recent studies that illustrate the advantages of metal–oxide and metal–carbide interfaces when aiming at the conversion of CO2 into methanol. CeOx/Cu(111), Cu/CeOx/TiO2(110), and Au/CeOx/TiO2(110) exhibit an activity for the CO2 → CH3OH conversion that is 2–3 orders of magnitude higher than that of a benchmark Cu(111) catalyst. In the Cu–ceria and Au–ceria interfaces, the multifunctional combination of metal and oxide centers leads to complementary chemical properties that open active reaction pathways for methanol synthesis. Efficient catalysts are also generated after depositing Cu and Au on TiC(001). In these cases, strong metal–support interactions modify the electronic properties of the admetals and make them active for the binding of CO2 and its subsequent transformation into CH3OH at the metal–carbide interfaces.

  5. West Nile Virus Activity in a Winter Roost of American Crows (Corvus brachyrhynchos): Is Bird-To-Bird Transmission Important in Persistence and Amplification?

    PubMed Central

    Hinton, M. G.; Reisen, W. K.; Wheeler, S. S.; Townsend, A. K.

    2015-01-01

    Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013–2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter. PMID:26335475

  6. West Nile Virus Activity in a Winter Roost of American Crows (Corvus brachyrhynchos): Is Bird-To-Bird Transmission Important in Persistence and Amplification?

    PubMed

    Hinton, M G; Reisen, W K; Wheeler, S S; Townsend, A K

    2015-07-01

    Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013-2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter.

  7. Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets--importance and approaches for laboratory animal research.

    PubMed

    Heindel, Jerrold J; vom Saal, Frederick S

    2008-03-01

    We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research.

  8. Purification and characterization of peptides from Capsicum annuum fruits which are α-amylase inhibitors and exhibit high antimicrobial activity against fungi of agronomic importance.

    PubMed

    Dos Santos, Layrana de Azevedo; Taveira, Gabriel Bonan; Ribeiro, Suzanna de Fátima Ferreira; Pereira, Lídia da Silva; Carvalho, André de Oliveira; Rodrigues, Rosana; Oliveira, Antônia Elenir Amâncio; Machado, Olga Lima Tavares; Araújo, Jucélia da Silva; Vasconcelos, Ilka Maria; Gomes, Valdirene Moreira

    2017-04-01

    Proteins extracted from Capsicum annuum L. fruits were initially subjected to reversed-phase chromatography on HPLC, resulting in eight peptide-rich fractions. All the fractions obtained were tested for their ability to inhibit porcine trypsin and amylase from both human saliva and from larval insect in vitro. All fractions were also tested for their ability to inhibit growth of the phytopathogenic fungi. Several fractions inhibited the activity of human salivary amylase and larval insect amylase, especially fraction Fa5. No fraction tested was found to inhibit trypsin activity, being Fa2 fraction an exception. Interestingly fraction Fa5 also displayed high antimicrobial activity against the species of the Fusarium genus. Fraction Fa5 was found to have two major protein bands of 17 and 6.5 kDa, and these were sequenced by mass spectrometry. Two peptides were obtained from the 6.5-kDa band, which showed similarity to antimicrobial peptides. Fraction Fa5 was also tested for its ability to permeabilize membranes and induce ROS. Fraction Fa5 was able to permeabilize the membranes of all the fungi tested. Fungi belonging to the genus Fusarium also showed an increase in the endogenous production of ROS when treated with this fraction. Antimicrobial peptides were also identified in the fruits from other Capsicum species.

  9. Probing the importance of hydrogen bonds in the active site of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

    PubMed

    Zheng, Zhong-liang; Ye, Mao-qing; Zuo, Zhen-yu; Liu, Zhi-gang; Tai, Keng-chang; Zou, Guo-lin

    2006-05-01

    Hydrogen bonds occurring in the catalytic triad (Asp32, His64 and Ser221) and the oxyanion hole (Asn155) are very important to the catalysis of peptide bond hydrolysis by serine proteases. For the subtilisin NK (nattokinase), a bacterial serine protease, construction and analysis of a three-dimensional structural model suggested that several hydrogen bonds formed by four residues function to stabilize the transition state of the hydrolysis reaction. These four residues are Ser33, Asp60, Ser62 and Thr220. In order to remove the effect of these hydrogen bonds, four mutants (Ser33-->Ala33, Asp60-->Ala60, Ser62-->Ala62, and Thr220-->Ala220) were constructed by site-directed mutagenesis. The results of enzyme kinetics indicated that removal of these hydrogen bonds increases the free-energy of the transition state (DeltaDeltaG(T)). We concluded that these hydrogen bonds are more important for catalysis than for binding the substrate, because removal of these bonds mainly affects the kcat but not the K(m) values. A substrate, SUB1 (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide), was used during enzyme kinetics experiments. In the present study we have also shown the results of FEP (free-energy perturbation) calculations with regard to the binding and catalysis reactions for these mutant subtilisins. The calculated difference in FEP also suggested that these four residues are more important for catalysis than binding of the substrate, and the simulated values compared well with the experimental values from enzyme kinetics. The results of MD (molecular dynamics) simulations further demonstrated that removal of these hydrogen bonds partially releases Asp32, His64 and Asn155 so that the stability of the transition state decreases. Another substrate, SUB2 (H-D-Val-Leu-Lys-p-nitroanilide), was used for FEP calculations and MD simulations.

  10. Evaluation of the Antibacterial Activity of Green Propolis Extract and Meadowsweet Extract Against Staphylococcus aureus Bacteria: Importance in Would Care Compounding Preparations.

    PubMed

    Lupatini, Nogueira Rodrigo José; Danopoulos, Panagiota; Swikidisa, Rosita; Alves, Pinheiro Vanessa

    2016-01-01

    The use of natural products in compounded wound care formulas is an exciting avenue to pursue for compounding pharmacists since these natural products may contain compounds that promote healing on their own. The use of these natural extracts as an alternative therapy for wound care may also provide several benefits, such as decreased inflammation, infection, side effects, and treatment costs. Thus far, several studies have demonstrated antimicrobial activity for various natural product extracts, including green propolis and meadowsweet. The antimicrobial properties of these extracts make them particularly interesting for wound care because the healing process is significantly delayed by bacterial infection and colonization at the site of injury. Therefore, to further investigate the antimicrobial properties of green propolis and meadowsweet extracts, we performed minimum inhibitory concentration and minimum bactericidal concentration assays against Staphylococcus aureus, a microorganism known to cause wound infections. The antimicrobial activity of green propolis and meadowsweet extracts was tested in vitro against a standard strain of Staphylococcus aureus in brain heart infusion broth and Mueller-Hinton agar plates. Green propolis extract demonstrated antimicrobial activity against Staphylococcus aureus with a minimum inhibitory concentration of 1.25 mg/mL and a minimum bactericidal concentration of 1.25 mg/mL. In contrast, meadowsweet extract failed to inhibit Staphylococcus aureus growth at the highest concentration tested (30 mg/mL). Green propolis was more effective than meadowsweet extract at inhibiting the growth of Staphylococcus aureus, suggesting that the addition of green propolis extract in wound care formulas might be more beneficial for the treatment of wounds. Therefore, we propose that green propolis extract is a promising natural product for wound care formulations.

  11. Extracellular Enzyme Activity and Microbial Diversity Measured on Seafloor Exposed Basalts from Loihi Seamount Indicate the Importance of Basalts to Global Biogeochemical Cycling

    PubMed Central

    Sylvan, Jason B.; Edwards, Katrina J.

    2014-01-01

    Seafloor basalts are widely distributed and host diverse prokaryotic communities, but no data exist concerning the metabolic rates of the resident microbial communities. We present here potential extracellular enzyme activities of leucine aminopeptidase (LAP) and alkaline phosphatase (AP) measured on basalt samples from different locations on Loihi Seamount, HI, coupled with analysis of prokaryotic biomass and pyrosequencing of the bacterial 16S rRNA gene. The community maximum potential enzyme activity (Vmax) of LAP ranged from 0.47 to 0.90 nmol (g rock)−1 h−1; the Vmax for AP was 28 to 60 nmol (g rock)−1 h−1. The Km of LAP ranged from 26 to 33 μM, while the Km for AP was 2 to 7 μM. Bacterial communities on Loihi basalts were comprised primarily of Alpha-, Delta-, andGammaproteobacteria, Bacteroidetes, and Planctomycetes. The putative ability to produce LAP is evenly distributed across the most commonly detected bacterial orders, but the ability to produce AP is likely dominated by bacteria in the orders Xanthomonadales, Flavobacteriales, and Planctomycetales. The enzyme activities on Loihi basalts were compared to those of other marine environments that have been studied and were found to be similar in magnitude to those from continental shelf sediments and orders of magnitude higher than any measured in the water column, demonstrating that the potential for exposed basalts to transform organic matter is substantial. We propose that microbial communities on basaltic rock play a significant, quantifiable role in benthic biogeochemical processes. PMID:24907315

  12. Tsetse GmmSRPN10 Has Anti-complement Activity and Is Important for Successful Establishment of Trypanosome Infections in the Fly Midgut

    PubMed Central

    Ooi, Cher-Pheng; Haines, Lee R.; Southern, Daniel M.; Lehane, Michael J.; Acosta-Serrano, Alvaro

    2015-01-01

    The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2–4 days. In this study, we identified four tsetse (Glossina morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission. PMID:25569180

  13. NMR structure of the noncytotoxic α-sarcin mutant Δ(7-22): The importance of the native conformation of peripheral loops for activity

    PubMed Central

    García-Mayoral, Ma Flor; García-Ortega, Lucia; Lillo, Ma Pilar; Santoro, Jorge; Martínez Del Pozo, Álvaro; Gavilanes, José G.; Rico, Manuel; Bruix, Marta

    2004-01-01

    The deletion mutant Δ(7-22) of α-sarcin, unlike its wild-type protein counterpart, lacks the specific ability to degrade rRNA in intact ribosomes and exhibits an increased unspecific ribonuclease activity and decreased interaction with lipid vesicles. In trying to shed light on these differences, we report here on the three-dimensional structure of the Δ(7-22) α-sarcin mutant using NMR methods. We also evaluated its dynamic properties on the basis of theoretical models and measured its correlation time (6.2 nsec) by time-resolved fluorescence anisotropy. The global fold characteristic of ribotoxins is preserved in the mutant. The most significant differences with respect to the α-sarcin structure are concentrated in (1) loop 2, (2) loop 3, which adopts a new orientation, and (3) loop 5, which shows multiple conformations and an altered dynamics. The interactions between loop 5 and the N-terminal hairpin are lost in the mutant, producing increased solvent accessibility of the active-site residues. The degree of solvent exposure of the catalytic His 137 is similar to that shown by His 92 in RNase T1. Additionally, the calculated order parameters of residues belonging to loop 5 in the mutant correspond to an internal dynamic behavior more similar to RNase T1 than α-sarcin. On the other hand, changes in the relative orientation of loop 3 move the lysine-rich region 111–114, crucial for substrate recognition, away from the active site. All of the structural and dynamic data presented here reveal that the mutant is a hybrid of ribotoxins and noncytotoxic ribonucleases, consistent with its biological properties. PMID:15044731

  14. The functional importance of a cap site-proximal region of the human prointerleukin 1 beta gene is defined by viral protein trans-activation.

    PubMed Central

    Hunninghake, G W; Monks, B G; Geist, L J; Monick, M M; Monroy, M A; Stinski, M F; Webb, A C; Dayer, J M; Auron, P E; Fenton, M J

    1992-01-01

    Prointerleukin 1 beta (IL-1 beta) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1 beta transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1 beta gene. We identified a protein, termed NFIL-1 beta A (NF beta A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1 beta genes. The IL-1 alpha gene, which lacks a TATA motif, does not possess an NF beta A-binding sequence within the promoter region, suggesting that NF beta A may selectively regulate IL-1 beta expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varies rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF beta A was assessed in transient transfection assays. These data indicate that NF beta A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF beta A in order to trans-activate the proximal IL-1 beta promoter in a monocytic cell line. We propose that NF beta A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation. Images PMID:1630455

  15. The Presidential Address 2013: Promoting Enthusiasm, Imparting Knowledge! Science for the General Population and Science for Future Researchers Must All Start in the School Curriculum

    ERIC Educational Resources Information Center

    Rees, Martin

    2013-01-01

    This article provides a transcript of the Presidential Address delivered by Martin Rees, Lord Rees of Ludlow, to the Association for Science Education (ASE) Annual Conference at the University of Reading, January 2013. The address is divided into five sections under the following headings: (1) Three Reasons Why the ASE's Mission Is So Important;…

  16. Studies on antimicrobial activity, in vitro, of Physalis angulata L. (Solanaceae) fraction and physalin B bringing out the importance of assay determination.

    PubMed

    Silva, Melissa T G; Simas, Sonia M; Batista, Terezinha G F M; Cardarelli, Paola; Tomassini, Therezinha C B

    2005-11-01

    Complex physalin metabolites present in the capsules of the fruit of Physalis angulata L. have been isolated and submitted to a series of assays of antimicrobial activity against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538P, Neisseria gonorrhoeae ATCC 49226, Escherichia coli ATCC 8739; E. coli ATCC 25922, Candida albicans ATCC 10231 applying different methodologies such as: bioautography, dilution broth, dilution agar, and agar diffusion techniques. A mixture of physalins (pool) containing physalins B, D, F, G inhibit S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538P, and N. gonorrhoeae ATCC 49226 at a concentration of 200 mg/microl, using agar dilution assays. The mixture was inactive against P. aeruginosa ATCC27853, E. coli ATCC 8739; E. coli ATCC 25922, C. albicans ATCC 10231 when applying bioautography assays. Physalin B (200 microg/ml) by the agar diffusion assay inhibited S. aureus ATCC 6538P by +/- 85%; and may be considered responsible for the antimicrobial activity.

  17. Mitogen-Activated Protein Kinase Cascade MKK7-MPK6 Plays Important Roles in Plant Development and Regulates Shoot Branching by Phosphorylating PIN1 in Arabidopsis

    PubMed Central

    Liang, Yan; Wu, Xiaowei; Cai, Yueyue; Zhang, Yuanya; Wang, Yingchun; Li, Jiayang; Wang, Yonghong

    2016-01-01

    Emerging evidences exhibit that mitogen-activated protein kinase (MAPK/MPK) signaling pathways are connected with many aspects of plant development. The complexity of MAPK cascades raises challenges not only to identify the MAPK module in planta but also to define the specific role of an individual module. So far, our knowledge of MAPK signaling has been largely restricted to a small subset of MAPK cascades. Our previous study has characterized an Arabidopsis bushy and dwarf1 (bud1) mutant, in which the MAP Kinase Kinase 7 (MKK7) was constitutively activated, resulting in multiple phenotypic alterations. In this study, we found that MPK3 and MPK6 are the substrates for phosphorylation by MKK7 in planta. Genetic analysis showed that MKK7-MPK6 cascade is specifically responsible for the regulation of shoot branching, hypocotyl gravitropism, filament elongation, and lateral root formation, while MKK7-MPK3 cascade is mainly involved in leaf morphology. We further demonstrated that the MKK7-MPK6 cascade controls shoot branching by phosphorylating Ser 337 on PIN1, which affects the basal localization of PIN1 in xylem parenchyma cells and polar auxin transport in the primary stem. Our results not only specify the functions of the MKK7-MPK6 cascade but also reveal a novel mechanism for PIN1 phosphorylation, establishing a molecular link between the MAPK cascade and auxin-regulated plant development. PMID:27618482

  18. The possibly important role played by Ga{sub 2}O{sub 3} during the activation of GaN photocathode

    SciTech Connect

    Fu, Xiaoqian E-mail: 214808748@qq.com; Wang, Honggang; Zhang, Junju; Li, Zhiming; Cui, Shiyao; Zhang, Lejuan

    2015-08-14

    Three different chemical solutions are used to remove the possible contamination on GaN surface, while Ga{sub 2}O{sub 3} is still found at the surface. After thermal annealing at 710 °C in the ultrahigh vacuum (UHV) chamber and activated with Cs/O, all the GaN samples are successfully activated to the effective negative electron affinity (NEA) photocathodes. Among all samples, the GaN sample with the highest content of Ga{sub 2}O{sub 3} after chemical cleaning obtains the highest quantum efficiency. By analyzing the property of Ga{sub 2}O{sub 3}, the surface processing results, and electron affinity variations during Cs and Cs/O{sub 2} deposition on GaN of other groups, it is suggested that before the adsorption of Cs, Ga{sub 2}O{sub 3} is not completely removed from GaN surface in our samples, which will combine with Cs and lead to a large decrease in electron affinity. Furthermore, the effective NEA is formed for GaN photocathode, along with the surface downward band bending. Based on this assumption, a new dipole model Ga{sub 2}O{sub 3}-Cs is suggested, and the experimental effects are explained and discussed.

  19. γ-Aminobutyric Acid Imparts Partial Protection from Salt Stress Injury to Maize Seedlings by Improving Photosynthesis and Upregulating Osmoprotectants and Antioxidants

    PubMed Central

    Wang, Yongchao; Gu, Wanrong; Meng, Yao; Xie, Tenglong; Li, Lijie; Li, Jing; Wei, Shi

    2017-01-01

    γ-Aminobutyric acid (GABA) has high physiological activity in plant stress physiology. This study showed that the application of exogenous GABA by root drenching to moderately (MS, 150 mM salt concentration) and severely salt-stressed (SS, 300 mM salt concentration) plants significantly increased endogenous GABA concentration and improved maize seedling growth but decreased glutamate decarboxylase (GAD) activity compared with non-treated ones. Exogenous GABA alleviated damage to membranes, increased in proline and soluble sugar content in leaves, and reduced water loss. After the application of GABA, maize seedling leaves suffered less oxidative damage in terms of superoxide anion (O2·−) and malondialdehyde (MDA) content. GABA-treated MS and SS maize seedlings showed increased enzymatic antioxidant activity compared with that of untreated controls, and GABA-treated MS maize seedlings had a greater increase in enzymatic antioxidant activity than SS maize seedlings. Salt stress severely damaged cell function and inhibited photosynthesis, especially in SS maize seedlings. Exogenous GABA application could reduce the accumulation of harmful substances, help maintain cell morphology, and improve the function of cells during salt stress. These effects could reduce the damage to the photosynthetic system from salt stress and improve photosynthesis and chlorophyll fluorescence parameters. GABA enhanced the salt tolerance of maize seedlings. PMID:28272438

  20. The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors.

    PubMed

    Trabelsi, Yosra; Amri, Mohamed; Becq, Hélène; Molinari, Florence; Aniksztejn, Laurent

    2017-02-01

    Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na(+) and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3-10 mM glutamate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR-excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO-treated compared with saline treated rats. Taken together our data demonstrate that the conversion of glutamate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2017;65:401-415.

  1. Copper (II) Adsorption by Activated Carbons from Pecan Shells: Effect of Oxygen Level During Activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural by-products represent a considerable quantity of harvested commodity crops. The use of by-products as precursors for the production of widely used adsorbents, such as activated carbons, may impart a value-added component of the overall biomass harvested. Our objective in this paper is...

  2. Metal Ion Adsorption by Activated Carbons Made from Pecan Shells: Effect of Oxygen Level During Activation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural by-products represent a considerable quantity of harvested commodity crops. The use of by-products as precursors for the production of widely used adsorbents, such as activated carbons, may impart a value-added component of the overall biomass harvested. Our objective in this presenta...

  3. The importance of the negative charge of beta-lactam compounds in the interactions with active-site serine DD-peptidases and beta-lactamases.

    PubMed Central

    Varetto, L; De Meester, F; Monnaie, D; Marchand-Brynaert, J; Dive, G; Jacob, F; Frère, J M

    1991-01-01

    The interaction between various penicillins and cephalosporins the carboxylate group of which at C-3 or C-4 had been esterified or amidated and different penicillin-recognizing enzymes was studied. In general, our findings reinforced the common assumption that an anionic group at that position is necessary for the effective acylation of these enzymes. However, the relative activities of the modified beta-lactams as inactivators of the Streptomyces R61 DD-peptidase or as substrates of the Bacillus licheniformis, Streptomyces albus G and Enterobacter cloacae beta-lactamases did not fit a general scheme in which the intrinsic electronic and geometric properties of the beta-lactam compounds would be sufficient to explain their substrate or inactivator properties towards the various types of enzymes investigated. PMID:1898366

  4. Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway.

    PubMed

    Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

    2016-01-01

    The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995-97 and in 2006-08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.

  5. Anti-nociceptive Activity of Ethnomedicinally Important Analgesic Plant Isodon rugosus Wall. ex Benth: Mechanistic Study and Identifications of Bioactive Compounds

    PubMed Central

    Zeb, Anwar; Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul

    2016-01-01

    Isodon rugosus Wall. ex Benth. is extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache, and generalized body pain. The current study is designed to scientifically verify the purported uses of I. rugosus as analgesic agent and to figure out its possible mechanism of action. Bioactive compounds responsible for analgesic activity were identified using GC and GC-MS analysis. Analgesic potentials were evaluated using acetic acid induced writhing, hot plate test, and formalin induced paw licking test. In acetic acid induced writhing chloroform fraction (Ir.Chf) exhibited 53% analgesia while formalin test displayed 61% inhibition at phase-I and 45% at phase-II respectively at a dose of 100 mg/kg. Similarly, in hot plate test Ir.Chf displayed average reaction time of 7 min at 15, 30, 45, and 60 min intervals. The possible mechanism of action was found to be the central pathway via opioidergic receptors as the mice showed morphine like analgesic activity at pre-administration of naloxone (opioid antagonist) in hot plate and formalin tests. In GC-MS analysis, 83 compounds were identified among which eight compounds including benzyl alcohol, sebacic acid, myristic acid, phytol, sugiol, Tocopherol, α-Amyrin, and stigmasterol were sorted out as previously reported analgesic compounds. Current study revealed that analgesic potential of I. rugosus can attributed to the presence of analgesic compounds. It may also be concluded that opioids receptors are involved in the analgesic mechanism of I. rugosus due to effective antagonism of nalaxone. PMID:27458379

  6. Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

    PubMed Central

    Fantin, B; Pierre, J; Castéla-Papin, N; Saint-Julien, L; Drugeon, H; Farinotti, R; Carbon, C

    1996-01-01

    The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus. PMID:8723470

  7. The importance of active surveillance, and immediate re-biopsy in low-risk prostate cancer: The largest series from Turkey

    PubMed Central

    Bayar, Göksel; Horasanlı, Kaya; Acinikli, Hüseyin; Tanrıverdi, Orhan; Dalkılıç, Ayhan; Arısan, Serdar

    2016-01-01

    Objective To evaluate long-term outcomes of active surveillance (AS) applied in low-risk prostate cancer patients, and the impact of re-biopsy results on the prediction of progression. Material and methods In our clinic, patients who had undergone AS for low-risk localized prostate cancer between the years 2005–2013 were included in the study. Our AS criteria are Gleason score ≤6, prostate-specific antigen (PSA) level <10 ng/mL, number of positive cores <3, maximum cancer involvement ratio <50% each core. Immediate re-biopsy (within 3 months) was performed to 65 patients who accepted AS. Finally, 43 patients who met re-biopsy criteria were included in the study. Prostate biopsy specimens were harvested from 12 cores under the guidance of transrectal ultrasound (TRUS). Re-biopsy was performed within 3 months (1–12 weeks). In re-biopsy, a total of 20 core biopsies were performed including the far lateral (6 cores) and transition zone (2 cores) in addition to standard 12 core biopsy. Our follow-up protocol is PSA measurement and digital rectal examination (DRE) every 3 months within the first 2 years, than every 6 months. Control biopsies was performed one year later and once upon every 3 years to patients whose PSA levels and DREs were normal at follow-up visits. More than 2 tumor invaded cores or 50% tumor in one core, and Gleason score exceeding 6 points were accepted as indications for definitive treatment. Patients were divided into two groups by re-biopsy results and compared according to the time to progression. We have done multivariate regression analysis to predict prognosis by using data on age, PSA level, and detection of tumor in re-biopsy specimens. Results Patients’ median age was 61 years and PSA level was 5 (2.7–9) ng/mL. Tumor was detected in 22 (34%) patients at re-biopsy and they underwent definitive treatment. Additionally tumor was detected in 9 patients, but active surveillance was maintained because their pathologic results met active

  8. BdorCSP2 Is Important for Antifeed and Oviposition-Deterring Activities Induced by Rhodojaponin-III against Bactrocera dorsalis

    PubMed Central

    Dong, Xiaolin; Wang, Peidan; Hu, Meiying; Zhong, Guohua

    2013-01-01

    Rhodojaponin-III is a nonvolatile botanical grayanoid diterpene compound, which has antifeedant and oviposition deterrence effects against many kinds of insects. However, the molecular mechanism of the chemoreception process remains unknown. In this study, the important role of BdorCSP2 in the recognition of Rhodojaponin-III was identified. The full length cDNA encoding BdorCSP2 was cloned from legs of Bactrocera dorsalis. The results of expression pattern revealed that BdorCSP2 was abundantly expressed in the legs of adult B. dorsalis. Moreover, the expression of BdorCSP2 could be up-regulated by Rhodojaponin-III. In order to gain comprehensive understanding of the recognition process, the binding affinity between BdorCSP2 and Rhodojaponin-III was measured by fluorescence binding assay. Silencing the expression of BdorCSP2 through the ingestion of dsRNA could weaken the effect of oviposition deterrence and antifeedant of Rhodojaponin-III. These results suggested that BdorCSP2 of B. dorsalis could be involved in chemoreception of Rhodojaponin-III and played a critical role in antifeedant and oviposition behaviors induced by Rhodojaponin-III. PMID:24155937

  9. Leucine residues in conserved region of 33K protein of bovine adenovirus - 3 are important for binding to major late promoter and activation of late gene expression.

    PubMed

    Kulshreshtha, Vikas; Islam, Azharul; Ayalew, Lisanework E; Tikoo, Suresh K

    2015-09-01

    The L6 region of bovine adenovirus 3 (BAdV-3) encode 33K (spliced) and 22K (unspliced) proteins. Earlier, anti-33K serum detected five major and three minor proteins in BAdV-3 infected cells. Here, we demonstrate that anti-sera raised against L6-22K protein detected two proteins of 42 and 37 kDa in BAdV-3 infected cells and one protein of 42 kDa in transfected cells expressing splice-site variant 22K protein (pC.22K containing substituted splice acceptor/donor sequence). Unlike 22K, 33K stimulated the transcription from the major late promoter (MLP) by binding to the downstream sequence elements (DE). Analysis of the variant proteins demonstrated that amino acids 201-240 of the conserved C-terminus of 33K containing the potential leucine zipper and RS repeat are required for the activation of MLP. Furthermore, amino acid substitution analysis demonstrated that unlike arginine residues of RS repeat, the leucine residues (217, 224, 232 and 240) of the conserved leucine zipper appear required for the binding of 33K to the MLP.

  10. Investigating Physical Activity in the Etiology of Pancreatic Cancer: The Age at Which This is Measured is Important and is Independent of Body Mass Index

    PubMed Central

    Noor, Nurulamin M.; Banim, Paul J.R.; Luben, Robert N.; Khaw, Kay-Tee; Hart, Andrew R.

    2015-01-01

    Objectives There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured, and if independent of body mass index (BMI). Methods 23 639 participants, aged 40-74 years, were recruited into the EPIC-Norfolk cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development and hazard ratios (HRs) were estimated, adjusted for covariates. Results Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend=1.06, 95% CI=0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs. lowest category HR=0.27, 95% CI=0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend=1.23, 95% CI=0.96-1.57). Including BMI in all models, produced similar estimates. Conclusions The reasons why PA in younger, but not older people, may prevent pancreatic cancer needs to be investigated. PA may operate through mechanisms independent of BMI. If this association is causal, one in six cases might be prevented by encouraging more PA. PMID:26390426

  11. Comparison of biomass from integrated fixed-film activated sludge (IFAS), moving bed biofilm reactor (MBBR) and membrane bioreactor (MBR) treating recalcitrant organics: Importance of attached biomass.

    PubMed

    Huang, Chunkai; Shi, Yijing; Xue, Jinkai; Zhang, Yanyan; Gamal El-Din, Mohamed; Liu, Yang

    2017-03-15

    This study compared microbial characteristics and oil sands process-affected water (OSPW) treatment performance of five types of microbial biomass (MBBR-biofilm, IFAS-biofilm, IFAS-floc, MBR-aerobic-floc, and MBR-anoxic-floc) cultivated from three types of bioreactors (MBBR, IFAS, and MBR) in batch experiments. Chemical oxygen demand (COD), ammonium, acid extractable fraction (AEF), and naphthenic acids (NAs) removals efficiencies were distinctly different between suspended and attached bacterial aggregates and between aerobic and anoxic suspended flocs. MBR-aerobic-floc and MBR-anoxic-floc demonstrated COD removal efficiencies higher than microbial aggregates obtained from MBBR and IFAS, MBBR and IFAS biofilm had higher AEF removal efficiencies than those obtained using flocs. MBBR-biofilm demonstrated the most efficient NAs removal from OSPW. NAs degradation efficiency was highly dependent on the carbon number and NA cyclization number according to UPLC/HRMS analysis. Mono- and di-oxidized NAs were the dominant oxy-NA species in OSPW samples. Microbial analysis with quantitative polymerase chain reaction (q-PCR) indicated that the bacterial 16S rRNA gene abundance was significantly higher in the batch bioreactors with suspended flocs than in those with biofilm, the NSR gene abundance in the MBR-anoxic bioreactor was significantly lower than that in aerobic batch bioreactors, and denitrifiers were more abundant in the suspended phase of the activated sludge flocs.

  12. Cosmic Rays trajectory reconstruction in the Earth Magnetosphere: External Field models importance during the last solar active period (from 2011 to 2013)

    NASA Astrophysics Data System (ADS)

    Grandi, Davide; Della Torre, Stefano; Pensotti, Simonetta; Bobik, Pavol; Kudela, Karel; Rancoita, Pier Giorgio; Gervasi, Massimo; Jeroen Boschini, Matteo; Rozza, Davide; La vacca, Giuseppe; Tacconi, Mauro

    Geomagsphere is a backtracing code for Cosmic Rays trajectory reconstruction in the Earth Magnetosphere that has been developed with last models of Internal (IGRF-11) and External (Tsyganenko 1996 and 2005) field components. This backtracing technique was used to separate Primary Cosmic Rays Particles, in case of allowed trajectory, from Secondary particles, in case of forbidden trajectory. We compared Magnetic Field measurements with and without the external field model with satellite data in past periods, in particular GOES (1998) and CLUSTER (2004) data. For both periods TS05 reproduces the magnetc field components with good accuracy. The specificity of the TS05 model, designed for solar storms, was tested comparing it with data taken by CLUSTER during the last solar active period (from 2011 to 2013) During Solar Flares (occurred march and May 2012), the usage of such an external field has a relevavant impact on fraction of AMS-02 cosmic rays identified as trapped and secondary particles, especially in high geomagnetic latitudes, as was expecte by some previous simulations, in comparison with the Internal Field only.

  13. Evidence for the importance of openness to experience on performance of a fluid intelligence task by physically active and inactive participants.

    PubMed

    Lochbaum, Marc R; Karoly, Paul; Landers, Daniel M

    2002-12-01

    The cross-sectional relationship between exercise training history and performance on a fluid intelligence test was examined. In addition, openness to experience was included as a potential trait-based contributor to predicting cognitive performance. Results supported past literature demonstrating that aerobically trained or active participants performed significantly better on the fluid intelligence task than aerobically untrained or inactive participants. Hierarchical regression analysis results revealed, as predicted, that openness to experience was a significant predictor of fluid intellectual performance. When entered into the hierarchical regression equation, openness to experience accounted for 16.0% of unique variance in Culture Fair Intelligence Test performance. By contrast, participants' exercise training history, which initially and significantly (p < .05) accounted for approximately 12.0% of the variance in cognitive performance, accounted for 5.0% (p > .05) after openness was entered. Participants were, on average, more open than inactive participants. Results are discussed in terms of the possible mechanisms aerobic exercise training and openness to experience share in regard to brain functioning and performance of fluid intelligence tasks. Future research is suggested that examines biological factors known to influence cognitive performance in exercise settings.

  14. Sensory effects of capsaicin congeners. Part II: Importance of chemical structure and pungency in desensitizing activity of capsaicin-type compounds.

    PubMed

    Szolcsányi, J; Jancsó-Gábor, A

    1976-01-01

    The characteristic insensitivity of sensory nerve endings to chemically induced pain brought about by capsaicin could be reproduced on the rat's eye by pungent vanillylamides, homovanilloyl-alkylamides and piperine, while homovanilloyl-cycloalkylamides, -azacycloalkylamides, - alkylesters, -alkyl-homovanillylamides, undecenoyl-3-aminopropranololand zingerone were practically ineffective in this respect. Desensitizing potency was not parallel with the stimulating effect of the compounds, e.g. the strongly pungent homovanilloyl-octylester failed to desensitize the receptors, while the less pungent homovanilloyl-dodecylamide proved to be a more potent desensitizing agent than capsaicin itself. It is concluded that the inverse position of the acylamide linkage does not modify, while its replacement by an esteric group completely abolishes the desensitizing activity. In contrast to the stimulating effect, in desensitizing action the presence of an alkyl chain is essential and its optimal length corresponds to 10-12 C atoms. On the basis of these results the possible molecular interactions at the site of action are discussed.

  15. Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin

    SciTech Connect

    Angel, T.; Gupta, S; Jastrzebska, B; Palczewski, K; Chance, M

    2009-01-01

    Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H2O18 solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.

  16. Evidence of the importance of the Met115 for Bacillus thuringiensis subsp. israelensis Cyt1Aa protein cytolytic activity in Escherichia coli.

    PubMed

    Zghal, Raida Zribi; Trigui, Hana; Ben Ali, Mamdouh; Jaoua, Samir

    2008-02-01

    Cyt1Aa is a cytolytic toxin, found together with the delta-endotoxins in Bacillus thuringiensis subsp. israelensis parasporal insecticidal crystals. The latter are used as an environmental friendly insecticide against mosquitoes and black flies. Contrary to Cry delta-endotoxin, the mode of action of Cyt1Aa is not completely understood. In the absence of direct structural data, a novel mutated cyt1Aa gene was used to obtain indirect informations on Cyt1Aa conformation changes in the lipid membrane environment. A mutated cyt1Aa gene named cyt1A97 has been isolated from a B. thuringiensis israelensis strain named BUPM97. The nucleotide sequence predicted a protein of 249 amino acids residues with a calculated molecular mass of 27 kDa. Both nucleotide and amino acid sequences similarity analysis revealed that cyt1A97 presents one amino acid different from the native cyt1Aa gene. This mutation was located in the helix alpha C corresponding to a substitution of Met(115) by a Thr. The heterologous expression of the cyt1A97 and another cyt1Aa-type gene called cyt1A98, not affected by such mutation used as control, was performed in Escherichia coli. It revealed that the mutated Cyt1A97 protein was over produced as inclusion bodies showing a very weak toxicity to E. coli contrarily to Cyt1A98 that stopped E. coli growth. Hence, hydrophobic residue Met at position 115 of Cyt1Aa should play a very important role for the maintenance of the structure and cytolytic functions of Cyt1Aa.

  17. Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

    SciTech Connect

    Sun, Yuan; Fujigaki, Yoshihide; Sakakima, Masanori; Hishida, Akira

    2010-02-15

    Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PT cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.

  18. Importance of π-stacking interactions in the hydrogen atom transfer reactions from activated phenols to short-lived N-oxyl radicals.

    PubMed

    Mazzonna, Marco; Bietti, Massimo; DiLabio, Gino A; Lanzalunga, Osvaldo; Salamone, Michela

    2014-06-06

    A kinetic study of the hydrogen atom transfer from activated phenols (2,6-dimethyl- and 2,6-di-tert-butyl-4-substituted phenols, 2,2,5,7,8-pentamethylchroman-6-ol, caffeic acid, and (+)-cathechin) to a series of N-oxyl radical (4-substituted phthalimide-N-oxyl radicals (4-X-PINO), 6-substituted benzotriazole-N-oxyl radicals (6-Y-BTNO), 3-quinazolin-4-one-N-oxyl radical (QONO), and 3-benzotriazin-4-one-N-oxyl radical (BONO)), was carried out by laser flash photolysis in CH3CN. A significant effect of the N-oxyl radical structure on the hydrogen transfer rate constants (kH) was observed with kH values that monotonically increase with increasing NO-H bond dissociation energy (BDENO-H) of the N-hydroxylamines. The analysis of the kinetic data coupled to the results of theoretical calculations indicates that these reactions proceed by a hydrogen atom transfer (HAT) mechanism where the N-oxyl radical and the phenolic aromatic rings adopt a π-stacked arrangement. Theoretical calculations also showed pronounced structural effects of the N-oxyl radicals on the charge transfer occurring in the π-stacked conformation. Comparison of the kH values measured in this study with those previously reported for hydrogen atom transfer to the cumylperoxyl radical indicates that 6-CH3-BTNO is the best N-oxyl radical to be used as a model for evaluating the radical scavenging ability of phenolic antioxidants.

  19. Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.

    PubMed

    Kundu, Paromita; Das, Manasi; Tripathy, Kalpalata; Sahoo, Sanjeeb K

    2016-12-21

    Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

  20. Multiplatform inversion of the 2013 Rim Fire smoke emissions using regional-scale modeling: important nocturnal fire activity, air quality, and climate impacts

    NASA Astrophysics Data System (ADS)

    Saide, P. E.; Peterson, D. A.; da Silva, A. M., Jr.; Ziemba, L. D.; Anderson, B.; Diskin, G. S.; Sachse, G. W.; Hair, J. W.; Butler, C. F.; Fenn, M. A.; Jimenez, J. L.; Campuzano Jost, P.; Dibb, J. E.; Yokelson, R. J.; Toon, B.; Carmichael, G. R.

    2014-12-01

    Large wildfire events are increasingly recognized for their adverse effects on air quality and visibility, thus providing motivation for improving smoke emission estimates. The Rim Fire, one of the largest events in California's history, produced a large smoke plume that was sampled by the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) DC-8 aircraft with a full suite of in-situ and remote sensing measurements on 26-27 August 2013. We developed an inversion methodology which uses the WRF-Chem modeling system to constrain hourly fire emissions, using as initial estimates the NASA Quick Fire Emissions Dataset (QFED). This method differs from the commonly performed top-down estimates that constrain daily (or longer time scale) emissions. The inversion method is able to simultaneously improve the model fit to various SEAC4RS airborne measurements (e.g., organic aerosol, carbon monoxide (CO), aerosol extinction), ground based measurements (e.g., AERONET aerosol optical depth (AOD), CO), and satellite data (MODIS AOD) by modifying fire emissions and utilizing the information content of all these measurements. Preliminary results show that constrained emissions for a 6 day period following the largest fire growth are a factor 2-4 higher than the initial top-down estimates. Moreover, there is a tendency to increase nocturnal emissions by factors sometimes larger than 20, indicating that vigorous fire activity continued during the night. This deviation from a typical diurnal cycle is confirmed using geostationary satellite data. The constrained emissions also have a larger day-to-day variability than the initial emissions and correlate better to daily area burned estimates as observed by airborne infrared measurements (NIROPS). Experiments with the assimilation system show that performing the inversion using only satellite AOD data produces much smaller correction factors than when using all available data

  1. Exhaustive mutagenesis of six secondary active-site residues in Escherichia coli chorismate mutase shows the importance of hydrophobic side chains and a helix N-capping position for stability and catalysis.

    PubMed

    Lassila, Jonathan Kyle; Keeffe, Jennifer R; Kast, Peter; Mayo, Stephen L

    2007-06-12

    Secondary active-site residues in enzymes, including hydrophobic amino acids, may contribute to catalysis through critical interactions that position the reacting molecule, organize hydrogen-bonding residues, and define the electrostatic environment of the active site. To ascertain the tolerance of an important model enzyme to mutation of active-site residues that do not directly hydrogen bond with the reacting molecule, all 19 possible amino acid substitutions were investigated in six positions of the engineered chorismate mutase domain of the Escherichia coli chorismate mutase-prephenate dehydratase. The six secondary active-site residues were selected to clarify results of a previous test of computational enzyme design procedures. Five of the positions encode hydrophobic side chains in the wild-type enzyme, and one forms a helix N-capping interaction as well as a salt bridge with a catalytically essential residue. Each mutant was evaluated for its ability to complement an auxotrophic chorismate mutase deletion strain. Kinetic parameters and thermal stabilities were measured for variants with in vivo activity. Altogether, we find that the enzyme tolerated 34% of the 114 possible substitutions, with a few mutations leading to increases in the catalytic efficiency of the enzyme. The results show the importance of secondary amino acid residues in determining enzymatic activity, and they point to strengths and weaknesses in current computational enzyme design procedures.

  2. A Cyclin Dependent Kinase Regulatory Subunit (CKS) Gene of Pigeonpea Imparts Abiotic Stress Tolerance and Regulates Plant Growth and Development in Arabidopsis.

    PubMed

    Tamirisa, Srinath; Vudem, Dashavantha R; Khareedu, Venkateswara R

    2017-01-01

    Frequent climatic changes in conjunction with other extreme environmental factors are known to affect growth, development and productivity of diverse crop plants. Pigeonpea, a major grain legume of the semiarid tropics, endowed with an excellent deep-root system, is known as one of the important drought tolerant crop plants. Cyclin dependent kinases (CDKs) are core cell cycle regulators and play important role in different aspects of plant growth and development. The cyclin-dependent kinase regulatory subunit gene (CKS) was isolated from the cDNA library of pigeonpea plants subjected to drought stress. Pigeonpea CKS (CcCKS) gene expression was detected in both the root and leaf tissues of pigeonpea and was upregulated by polyethylene glycol (PEG), mannitol, NaCl and abscisic acid (ABA) treatments. The overexpression of CcCKS gene in Arabidopsis significantly enhanced tolerance of transgenics to drought and salt stresses as evidenced by different physiological parameters. Under stress conditions, transgenics showed higher biomass, decreased rate of water loss, decreased MDA levels, higher free proline contents, and glutathione levels. Moreover, under stress conditions transgenics exhibited lower stomatal conductance, lower transpiration, and higher photosynthetic rates. However, under normal conditions, CcCKS-transgenics displayed decreased plant growth rate, increased cell size and decreased stomatal number compared to those of wild-type plants. Real-time polymerase chain reaction revealed that CcCKS could regulate the expression of both ABA-dependent and ABA-independent genes associated with abiotic stress tolerance as well as plant growth and development. As such, the CcCKS seems promising and might serve as a potential candidate gene for enhancing the abiotic stress tolerance of crop plants.

  3. A Cyclin Dependent Kinase Regulatory Subunit (CKS) Gene of Pigeonpea Imparts Abiotic Stress Tolerance and Regulates Plant Growth and Development in Arabidopsis

    PubMed Central

    Tamirisa, Srinath; Vudem, Dashavantha R.; Khareedu, Venkateswara R.

    2017-01-01

    Frequent climatic changes in conjunction with other extreme environmental factors are known to affect growth, development and productivity of diverse crop plants. Pigeonpea, a major grain legume of the semiarid tropics, endowed with an excellent deep-root system, is known as one of the important drought tolerant crop plants. Cyclin dependent kinases (CDKs) are core cell cycle regulators and play important role in different aspects of plant growth and development. The cyclin-dependent kinase regulatory subunit gene (CKS) was isolated from the cDNA library of pigeonpea plants subjected to drought stress. Pigeonpea CKS (CcCKS) gene expression was detected in both the root and leaf tissues of pigeonpea and was upregulated by polyethylene glycol (PEG), mannitol, NaCl and abscisic acid (ABA) treatments. The overexpression of CcCKS gene in Arabidopsis significantly enhanced tolerance of transgenics to drought and salt stresses as evidenced by different physiological parameters. Under stress conditions, transgenics showed higher biomass, decreased rate of water loss, decreased MDA levels, higher free proline contents, and glutathione levels. Moreover, under stress conditions transgenics exhibited lower stomatal conductance, lower transpiration, and higher photosynthetic rates. However, under normal conditions, CcCKS-transgenics displayed decreased plant growth rate, increased cell size and decreased stomatal number compared to those of wild-type plants. Real-time polymerase chain reaction revealed that CcCKS could regulate the expression of both ABA-dependent and ABA-independent genes associated with abiotic stress tolerance as well as plant growth and development. As such, the CcCKS seems promising and might serve as a potential candidate gene for enhancing the abiotic stress tolerance of crop plants. PMID:28239388

  4. Importance of Effective Listening Infomercial

    ERIC Educational Resources Information Center

    Johnson-Curiskis, Nanette

    2009-01-01

    This article details an activity intended for use in a course with a unit on effective listening, including listening courses, public speaking, and interpersonal communication. Students will explain the importance of effective and active listening for a target audience by producing an infomercial for a product or service which they design.

  5. Food as medicine in psychiatric care: which profession should be responsible for imparting knowledge and use of omega-3 fatty acids in psychiatry.

    PubMed

    Johannessen, Berit; Skagestad, Ingjerd; Bergkaasa, Anne Mari

    2011-05-01

    The effect of omega-3 fatty acids on depression is well documented. The purpose of this study was to determine if and how food is used as medicine in psychiatric care, especially how omega-3 fatty acids are used as a supplement in the treatment of depression. This is a pilot study with a qualitative design using questionnaires and interviews among nursing students, tutor nurses and psychiatrists. Three main categories emerged: 1. Nutrition is considered important but few evaluations are made. 2. There was a lack of knowledge of the effects of Omega 3. 3. There was an unclear division of responsibility among health personnel. A change in knowledge paradigms and clarification of responsibility is called for if food-as-medicine is to take its true place in psychiatric care. It is also necessary to include CAM and holistic perspectives. Further research is needed to determine why health education and health workers do not focus on nutrition therapy in psychiatric care. Further research is also needed to reveal both the patients, the GPs and the CAM practitioners' knowledge and attitude to the use of dietary supplements.

  6. Alteration of flavonoid accumulation patterns in transparent testa mutants disturbs auxin transport, gravity responses, and imparts long-term effects on root and shoot architecture.

    PubMed

    Buer, Charles S; Kordbacheh, Farzanah; Truong, Thy T; Hocart, Charles H; Djordjevic, Michael A

    2013-07-01

    Flavonoids have broad cross-kingdom biological activity. In Arabidopsis, flavonoid accumulation in specific tissues, notably the root elongation zone and root/shoot junction modulate auxin transport, affect root gravitropism, and influence overall plant architecture. The relative contribution made by aglycones and their glycosides remains undetermined, and the longer-term phenotypic effects of altered flavonoid accumulation are not fully assessed. We tested Arabidopsis thaliana mutants that accumulate different flavonoids to determine which flavonoids were causing these affects. Tandem mass spectrometry and in situ fluorescence localisation were used to determine the in vivo levels of aglycones in specific tissues of 11 transparent testa mutants. We measured rootward and shootward auxin transport, gravitropic responses, and identified the long-term changes to root and shoot architecture. Unexpected aglycone species accumulated in vivo in several flavonoid-pathway mutants, and lower aglycone levels occurred in transcription factor mutants. Mutants accumulating more quercetin and quercetin-glycosides changed the greatest in auxin transport, gravitropism, and aerial tissue growth. Early flavonoid-pathway mutants showed aberrant lateral root initiation patterns including clustered lateral root initiations at a single site. Transcription factor mutants had multiple phenotypes including shallow root systems. These results confirm that aglycones are present at very low levels, show that lateral root initiation is perturbed in early flavonoid-pathway mutants, and indicate that altered flavonoid accumulation affects multiple aspects of plant architecture.

  7. Molecular characterization of ZzR1 resistance gene from Zingiber zerumbet with potential for imparting Pythium aphanidermatum resistance in ginger.

    PubMed

    Nair, R Aswati; Thomas, George

    2013-03-01

    Soft rot disease caused by the oomycete Pythium aphanidermatum (Edson) Fitzp. is the most economically significant disease of ginger (Zingiber officinale Rosc.) in tropical countries. All available ginger cultivars are susceptible to this pathogen. However a wild ginger relative viz., Zingiber zerumbet L. Smith, was identified as a potential soft rot resistance donor. In the present study, a putative resistance (R) gene designated, ZzR1 was isolated and characterized from Z. zerumbet using sequence information from Zingiber RGCs identified in our earlier experiments. Analysis of the 2280 bp segment revealed a 2157 bp open reading frame (ORF) encoding a putative cytoplasmically localized protein. The deduced ZzR1 protein shared high homology with other known R-genes belonging to the CC-NBS-LRR (coiled coil-nucleotide binding site-leucine rich repeat) class and had a calculated molecular weight of 84.61kDa. Real-time PCR analysis of ZzR1 transcription in Z. zerumbet following pathogen infection demonstrated activation at 3 hpi thus suggesting an involvement of ZzR1 in Z. zerumbet defense mechanism. Although many R-genes have been characterized from different taxa, none of them will help in the development of resistant ginger cultivars owing to the phenomenon of "Restricted Taxonomic Functionality" (RTF). Thus ZzR1 gene characterized from the resistant wild Zingiber accession represents a valuable genomic resource for ginger improvement programs. This first report on R-gene isolation from the Zingiber secondary gene pool is pivotal in designing strategies for engineering resistance in ginger, which is otherwise not amenable to conventional improvement programs owing to sexual reproduction barriers.

  8. The Staphylococcus aureus SrrAB Regulatory System Modulates Hydrogen Peroxide Resistance Factors, Which Imparts Protection to Aconitase during Aerobic Growth

    PubMed Central

    Mashruwala, Ameya A.; Boyd, Jeffrey M.

    2017-01-01

    The SrrAB two-component regulatory system (TCRS) positively influences the transcription of genes involved in aerobic respiration in response to changes in respiratory flux. Hydrogen peroxide (H2O2) can arise as a byproduct of spontaneous interactions between dioxygen and components of respiratory pathways. H2O2 damages cellular factors including protein associated iron-sulfur cluster prosthetic groups. We found that a Staphylococcus aureus strain lacking the SrrAB two-component regulatory system (TCRS) is sensitive to H2O2 intoxication. We tested the hypothesis that SrrAB manages the mutually inclusive expression of genes required for aerobic respiration and H2O2 resistance. Consistent with our hypothesis, a ΔsrrAB strain had decreased transcription of genes encoding for H2O2 resistance factors (kat, ahpC, dps). SrrAB was not required for the inducing the transcription of these genes in cells challenged with H2O2. Purified SrrA bound to the promoter region for dps suggesting that SrrA directly influences dps transcription. The H2O2 sensitivity of the ΔsrrAB strain was alleviated by iron chelation or deletion of the gene encoding for the peroxide regulon repressor (PerR). The positive influence of SrrAB upon H2O2 metabolism bestowed protection upon the solvent accessible iron-sulfur (FeS) cluster of aconitase from H2O2 poisoning. SrrAB also positively influenced transcription of scdA (ytfE), which encodes for a FeS cluster repair protein. Finally, we found that SrrAB positively influences H2O2 resistance only during periods of high dioxygen-dependent respiratory activity. SrrAB did not influence H2O2 resistance when cellular respiration was diminished as a result of decreased dioxygen availability, and negatively influenced it in the absence of respiration (fermentative growth). We propose a model whereby SrrAB-dependent regulatory patterns facilitate the adaptation of cells to changes in dioxygen concentrations, and thereby aids in the prevention of H2O2

  9. Progastrin overexpression imparts tumorigenic/metastatic potential to embryonic epithelial cells: phenotypic differences between transformed and non-transformed stem cells

    PubMed Central

    Sarkar, Shubhashish; Kantara, Carla; Ortiz, Ixiu; Swiercz, Rafal; Kuo, Joyce; Davey, Robert; Escobar, Kenneth; Ullrich, Robert; Singh, Pomila

    2012-01-01

    We recently reported that overexpression of progastrin in embryonic epithelial cells (HEKmGAS-cells) increased proliferation of the cells, compared to that of control HEKC-cells. Here we report the novel finding that tumorigenic and metastatic potential of HEKmGAS cells is also increased significantly, compared to that of HEKC cells. Cell-surface associated annexinA2 (CS-ANXA2) binds progastrin and is over-expressed on cancer-cells, allowing us to successfully use fluorescently-labeled progastrin-peptide for enumerating metastatic lesions of transformed/cancer cells in vivo. Next, we examined the hypothesis that increased tumorigenic/metastatic potential of isogenic HEKmGAS vs HEKC cells maybe due to transformed-phenotype of stem-cells. FACSorting/FACScanning of cells demonstrated significant increases in percent DCLK1/Lgr5 positive stem-cells, co-expressing CD44/CS-ANXA2, in HEKmGAS vs HEKC-cells. Distinct differences were noted in morphology of HEKC vs HEKmGAS spheroidal growths on non-adherent cultures (selective for stem cells). HEKC-spheroids were rounded with distinct perimeters (basement membranes?), while HEKmGAS-spheroids were amorphous, with no perimeters. Relative levels of DCLK1/Lgr5/CD44 and AnnexinA2/β-catenin/pNFκBp65/metalloproteinases were significantly increased in HEKmGAS vs HEKC-cells, growing either as mono-layer cultures, 3D-spheroids (in vitro), or xenografts (in vivo). Interestingly, HEKC-cells enriched for CS-ANXA2, developed amorphous spheroids, while down-regulation of ANXA2 in HEKmGAS-clones, resulted in loss of matrixmetalloproteinases and re-formation of rounded spheroids, suggesting high levels of CS-ANXA2/matrixmetalloproteinases may impact spheroid morphology. Down-regulation of DCLK1 significantly attenuated activation of β-catenin, with loss of proliferation of HEKmGAS and HEKC-cells, suggesting DCLK1 is required for maintaining proliferation of cells. Conclusions Our results suggest the novel possibility that transformed stem

  10. Interdisciplinary Robotic Activity Hones Important Skills

    ERIC Educational Resources Information Center

    Black, Dan; Zeigler, Jodi

    2011-01-01

    As educators, the authors believe in guiding students towards the life skills, knowledge, and expertise they need to succeed in life and in the workforce of the 21st century. With that in mind, they have created a project in which students drive their own learning through creativity and collaborative work to develop an efficient product. Through…

  11. Core Noise - Increasing Importance

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart S.

    2011-01-01

    This presentation is a technical summary of and outlook for NASA-internal and NASA-sponsored external research on core (combustor and turbine) noise funded by the Fundamental Aeronautics Program Subsonic Fixed Wing (SFW) Project. Sections of the presentation cover: the SFW system-level noise metrics for the 2015, 2020, and 2025 timeframes; turbofan design trends and their aeroacoustic implications; the emerging importance of core noise and its relevance to the SFW Reduced-Perceived-Noise Technical Challenge; and the current research activities in the core-noise area, with additional details given about the development of a high-fidelity combustor-noise prediction capability as well as activities supporting the development of improved reduced-order, physics-based models for combustor-noise prediction. The need for benchmark data for validation of high-fidelity and modeling work and the value of a potential future diagnostic facility for testing of core-noise-reduction concepts are indicated. The NASA Fundamental Aeronautics Program has the principal objective of overcoming today's national challenges in air transportation. The SFW Reduced-Perceived-Noise Technical Challenge aims to develop concepts and technologies to dramatically reduce the perceived aircraft noise outside of airport boundaries. This reduction of aircraft noise is critical to enabling the anticipated large increase in future air traffic. Noise generated in the jet engine core, by sources such as the compressor, combustor, and turbine, can be a significant contribution to the overall noise signature at low-power conditions, typical of approach flight. At high engine power during takeoff, jet and fan noise have traditionally dominated over core noise. However, current design trends and expected technological advances in engine-cycle design as well as noise-reduction methods are likely to reduce non-core noise even at engine-power points higher than approach. In addition, future low-emission combustor

  12. Routine Breakers for Emotionally Active Learning: "A Case Study"

    ERIC Educational Resources Information Center

    Munoz-Luna, Rosa; Jurado-Navas, Antonio

    2016-01-01

    The present paper aims to present a typology of classroom activities which may serve as group driving dynamics to improve student attention in class. Human attention skills may have been shortened now and traditional ways of imparting knowledge should be modified (Soslau, 2015). As a consequence, this implies multi-tasking behaviour as users…

  13. The importance of cohesion and enjoyment for the fitness improvement of 8-10-year-old children participating in a team and individual sport school-based physical activity intervention.

    PubMed

    Elbe, Anne-Marie; Wikman, Johan Michael; Zheng, Miky; Larsen, Malte Nejst; Nielsen, Glen; Krustrup, Peter

    2017-04-01

    This study investigates the enjoyment and cohesion of school children participating in a school-based high-intensity physical activity (PA) intervention. Both enjoyment and cohesion have been found to be important factors for adherence to regular physical and sport activity, an important outcome of PA interventions. The sample consisted of 300 pupils (mean age: 9.3 years; 52.7% female) assigned to a team sport intervention, an individual sport intervention, or a control group for 10 months. The Physical Activity Enjoyment Scale and Youth Sport Environment Questionnaire were used to measure enjoyment and cohesion. The Yo-Yo IR1C test determined fitness improvements. Results showed that enjoyment and cohesion (social) measured at the beginning of the intervention significantly predict fitness improvements achieved after 10 months. No differing developmental effects over time could be found in the intervention groups with regard to cohesion and enjoyment when comparing them to the control group. However, enjoyment and cohesion (social) significantly decreased in the groups that performed individual sports. Team sports seem to be more advantageous for the development of enjoyment and cohesion, which are both factors that positively impact the health outcomes of the intervention.

  14. Python import replacement

    SciTech Connect

    2011-10-01

    SmartImport.py is a Python source-code file that implements a replacement for the standard Python module importer. The code is derived from knee.py, a file in the standard Python diestribution , and adds functionality to improve the performance of Python module imports in massively parallel contexts.

  15. High Brightness Fluorescent White Polymer Light-Emitting Diodes by Promoted Hole Injection via Reduced Barrier by Interfacial Dipole Imparted from Chlorinated Indium Tin Oxide to the Hole Injection Layer PEDOT:PSS.

    PubMed

    Syue, Hong-Ren; Hung, Miao-Ken; Chang, Yao-Tang; Lin, Ge-Wei; Lee, Yu-Hsuan; Chen, Show-An

    2017-02-01

    We demonstrated that introducing poly(3,4-ethylenedioxythiophene) polystyrene sulfonate as a hole transport layer (HTL) on top of chlorinated indium tin oxide (Cl-ITO) anode can lead to a deeper highest occupied molecular orbital level of the HTL (promoting from 5.22 to 5.42 eV) due to the interfacial dipole imparted by the Cl-ITO, which allows barrier-free hole injection to the emitting layer with polyspirobifluorene doped with the yellow emitter rubrene and significantly prevents excitons quenching by residual chlorine radicals on the surface of Cl-ITO. By use of poly[9,9-bis(6'-(18-crown-6)methoxy)hexyl)fluorene] chelating to potassium ion (PFCn6:K(+)) as electron injection layer and air-stable high work function (EΦ) metal aluminum as the cathode, the performance of fluorescent white polymer light-emitting diode (WPLED) achieves the high maximum brightness (Bmax) of 61 523 cd/m(2) and maximum luminance efficiency (ηL, max) of 10.3 cd/A. Replacing PFCn6:K(+)/Al cathode by CsF/Al, the Bmax and ηL, max are promoted to 87 615 cd/m(2) (the record value in WPLED) and 11.1 cd/A, respectively.

  16. The Importance of Critical Literacy

    ERIC Educational Resources Information Center

    Janks, Hilary

    2012-01-01

    This paper is divided into three parts. It begins by making an argument for the ongoing importance of critical literacy at a moment when there are mutterings about its being passe. The second part of the paper formulates the argument with the use of illustrative texts. It concludes with examples of critical literacy activities that I argue, are…

  17. C-H Bond Activation of Methane by PtII-N-Heterocyclic Carbene Complexes. The Importance of Having the Ligands in the Right Place at the Right Time

    SciTech Connect

    Prince, Bruce M.; Cundari, Thomas R

    2012-02-13

    A DFT study of methane C–H activation barriers for neutral NHC–PtII–methoxy complexes yielded 22.8 and 26.1 kcal/mol for oxidative addition (OA) and oxidative hydrogen migration (OHM), respectively. Interestingly, this is unlike the case for cationic NHC–PtII–methoxy complexes, whereby OHM entails a calculated barrier of 26.9 kcal/mol but the OA barrier is only 14.4 kcal/mol. Comparing transition state (TS) and ground state (GS) geometries implies an ~10 kcal/mol “penalty” to the barriers arising from positioning the NHC and OMe ligands into a relative orientation that is preferred in the GS to the orientation that is favored in the TS. The results thus imply an intrinsic barrier arising from C–H scission of ~15 ± 2 kcal/mol for NHC–PtII–methoxy complexes. Calculations show the importance of designing C–H activation catalysts where the GS active species is already structurally “prepared” and which either does not need to undergo any geometric perturbations to access the methane C–H activation TS or is not energetically prohibited from such perturbations.

  18. RBOH1-dependent H2O2 production and subsequent activation of MPK1/2 play an important role in acclimation-induced cross-tolerance in tomato

    PubMed Central

    Zhou, Yan-Hong; Yu, Jing-Quan

    2014-01-01

    H2O2 and mitogen-activated protein kinase (MAPK) cascades play important functions in plant stress responses, but their roles in acclimation response remain unclear. This study examined the functions of H2O2 and MPK1/2 in acclimation-induced cross-tolerance in tomato plants. Mild cold, paraquat, and drought as acclimation stimuli enhanced tolerance to more severe subsequent chilling, photooxidative, and drought stresses. Acclimation-induced cross-tolerance was associated with increased transcript levels of RBOH1 and stress- and defence-related genes, elevated apoplastic H2O2 accumulation, increased activity of NADPH oxidase and antioxidant enzymes, reduced glutathione redox state, and activation of MPK1/2 in tomato. Virus-induced gene silencing of RBOH1, MPK1, and MPK2 or MPK1/2 all compromised acclimation-induced cross-tolerance and associated stress responses. Taken together, these results strongly suggest that acclimation-induced cross-tolerance is largely attributed to RBOH1-dependent H2O2 production at the apoplast, which may subsequently activate MPK1/2 to induce stress responses. PMID:24323505

  19. RBOH1-dependent H2O2 production and subsequent activation of MPK1/2 play an important role in acclimation-induced cross-tolerance in tomato.

    PubMed

    Zhou, Jie; Xia, Xiao-Jian; Zhou, Yan-Hong; Shi, Kai; Chen, Zhixiang; Yu, Jing-Quan

    2014-02-01

    H2O2 and mitogen-activated protein kinase (MAPK) cascades play important functions in plant stress responses, but their roles in acclimation response remain unclear. This study examined the functions of H2O2 and MPK1/2 in acclimation-induced cross-tolerance in tomato plants. Mild cold, paraquat, and drought as acclimation stimuli enhanced tolerance to more severe subsequent chilling, photooxidative, and drought stresses. Acclimation-induced cross-tolerance was associated with increased transcript levels of RBOH1 and stress- and defence-related genes, elevated apoplastic H2O2 accumulation, increased activity of NADPH oxidase and antioxidant enzymes, reduced glutathione redox state, and activation of MPK1/2 in tomato. Virus-induced gene silencing of RBOH1, MPK1, and MPK2 or MPK1/2 all compromised acclimation-induced cross-tolerance and associated stress responses. Taken together, these results strongly suggest that acclimation-induced cross-tolerance is largely attributed to RBOH1-dependent H2O2 production at the apoplast, which may subsequently activate MPK1/2 to induce stress responses.

  20. Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras.

    PubMed

    Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

    2011-11-01

    Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome-related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome-related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era.

  1. Emergy and Its Importance

    EPA Science Inventory

    Emergy is an important quantity needed for public policy analysis that is based on a complex methodology. The intent of this Environmental Research Brief is to define emergy and its importance in a manner that is accessible to everyone with at least a high school education. Emer...

  2. In vitro and in vivo characterization of opioid activities of endomorphins analogs with novel constrained C-terminus: evidence for the important role of proper spatial disposition of the third aromatic ring.

    PubMed

    Yu, Ye; Shao, Xuan; Wang, Chang-Lin; Liu, Hong-Mei; Cui, Yun; Fan, Ying-Zhe; Liu, Jing; Wang, Rui

    2007-04-01

    In the present study, the C-terminus of endomorphin (Tyr(1)-Pro(2)-Trp/Phe(3)-Phe(4)-NH(2), EMs) analogs [Xaa(4)-R]EMs, modified by substitution of a non-aromatic residue for Phe(4) and ending up with -NH-benzyl, were designed to generate an atypical conformationally constrained peptide set. We investigated the effects of these analogs on the opioid receptors affinity, guinea pig ileum (GPI) and mouse vas deferens (MVD) activity, system arterial pressure (SAP), heart rate (HR), antinociception and colonic motility. Analogs 5 ([D-V(4)-Bzl]EM1) and 10 ([D-V(4)-Bzl]EM2), which exhibit appropriate spatial orientations of the third aromatic ring, were about 3-4 times more potent than their parents both in vivo and in vitro. However, a drastic loss of activity was found in analogs 2 ([A(4)-Bzl]EM1) and 7 ([A(4)-Bzl]EM2), which possess improper spatial orientations of the third aromatic ring. Interestingly, analog 7 or 3 ([G(4)-Bzl]EM1), when injected intravenously (i.v.), produced significantly different changes in SAP from their parents. Surprisingly, analog 4 displayed relatively higher vasodepressor activity but significantly less potent colonic contractile activity than analog 5. This may be elicited by the differences in the spatial disposition of the third aromatic ring, which were verified by molecular modeling. Our results indicate that the proper spatial disposition of the third aromatic ring plays an important role in the regulation of pharmacological activities of EMs.

  3. Ciliary Entry of the Hedgehog Transcriptional Activator Gli2 Is Mediated by the Nuclear Import Machinery but Differs from Nuclear Transport in Being Imp-α/β1-Independent.

    PubMed

    Torrado, Belén; Graña, Martín; Badano, José L; Irigoín, Florencia

    2016-01-01

    Gli2 is the primary transcriptional activator of Hedgehog signalling in mammals. Upon stimulation of the pathway, Gli2 moves into the cilium before reaching the nucleus. However, the mechanisms underlying its entry into the cilium are not completely understood. Since several similarities have been reported between nuclear and ciliary import, we investigated if the nuclear import machinery participates in Gli2 ciliary entry. Here we show that while two conserved classical nuclear localization signals mediate Gli2 nuclear localization via importin (Imp)-α/β1, these sequences are not required for Gli2 ciliary import. However, blocking Imp-mediated transport through overexpression of GTP-locked Ran reduced the percentage of Gli2 positive cilia, an effect that was not explained by increased CRM1-dependent export of Gli2 from the cilium. We explored the participation of Imp-β2 in Gli2 ciliary traffic and observed that this transporter is involved in moving Gli2 into the cilium, as has been described for other ciliary proteins. In addition, our data indicate that Imp-β2 might also collaborate in Gli2 nuclear entry. How does Imp-β2 determine the final destination of a protein that can localize to two distinct subcellular compartments remains an open question. Therefore, our data shows that the nuclear-cytoplasmic shuttling machinery plays a critical role mediating the subcellular distribution of Gli2 and the activation of the pathway, but distinct importins likely play a differential role mediating its ciliary and nuclear translocation.

  4. Ciliary Entry of the Hedgehog Transcriptional Activator Gli2 Is Mediated by the Nuclear Import Machinery but Differs from Nuclear Transport in Being Imp-α/β1-Independent

    PubMed Central

    Torrado, Belén; Graña, Martín; Badano, José L.; Irigoín, Florencia

    2016-01-01

    Gli2 is the primary transcriptional activator of Hedgehog signalling in mammals. Upon stimulation of the pathway, Gli2 moves into the cilium before reaching the nucleus. However, the mechanisms underlying its entry into the cilium are not completely understood. Since several similarities have been reported between nuclear and ciliary import, we investigated if the nuclear import machinery participates in Gli2 ciliary entry. Here we show that while two conserved classical nuclear localization signals mediate Gli2 nuclear localization via importin (Imp)-α/β1, these sequences are not required for Gli2 ciliary import. However, blocking Imp-mediated transport through overexpression of GTP-locked Ran reduced the percentage of Gli2 positive cilia, an effect that was not explained by increased CRM1-dependent export of Gli2 from the cilium. We explored the participation of Imp-β2 in Gli2 ciliary traffic and observed that this transporter is involved in moving Gli2 into the cilium, as has been described for other ciliary proteins. In addition, our data indicate that Imp-β2 might also collaborate in Gli2 nuclear entry. How does Imp-β2 determine the final destination of a protein that can localize to two distinct subcellular compartments remains an open question. Therefore, our data shows that the nuclear-cytoplasmic shuttling machinery plays a critical role mediating the subcellular distribution of Gli2 and the activation of the pathway, but distinct importins likely play a differential role mediating its ciliary and nuclear translocation. PMID:27579771

  5. Multiple Conserved Domains of the Nucleoporin Nup124p and Its Orthologs Nup1p and Nup153 Are Critical for Nuclear Import and Activity of the Fission Yeast Tf1 Retrotransposon

    PubMed Central

    Sistla, Srivani; Pang, Junxiong Vincent; Wang, Cui Xia

    2007-01-01

    The nucleoporin Nup124p is a host protein required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr in fission yeast. The human nucleoporin Nup153 and the Saccharomyces cerevisiae Nup1p were identified as orthologs of Nup124p. In this study, we show that all three nucleoporins share a large FG/FXFG-repeat domain and a C-terminal peptide sequence, GRKIxxxxxRRKx, that are absolutely essential for Tf1 retrotransposition. Though the FXFG domain was essential, the FXFG repeats themselves could be eliminated without loss of retrotransposon activity, suggesting the existence of a common element unrelated to FG/FXFG motifs. The Nup124p C-terminal peptide, GRKIAVPRSRRKR, was extremely sensitive to certain single amino acid changes within stretches of the basic residues. On the basis of our comparative study of Nup124p, Nup1p, and Nup153 domains, we have developed peptides that specifically knockdown retrotransposon activity by disengaging the Tf1-Gag from its host nuclear transport machinery without any harmful consequence to the host itself. Our results imply that those domains challenged a specific pathway affecting Tf1 transposition. Although full-length Nup1p or Nup153 does not complement Nup124p, the functionality of their conserved domains with reference to Tf1 activity suggests that these three proteins evolved from a common ancestor. PMID:17615301

  6. T helper cell activation and human retroviral pathogenesis.

    PubMed Central

    Copeland, K F; Heeney, J L

    1996-01-01

    T helper (Th) cells are of central importance in regulating many critical immune effector mechanisms. The profile of cytokines produced by Th cells correlates with the type of effector cells induced during the immune response to foreign antigen. Th1 cells induce the cell-mediated immune response, while Th2 cells drive antibody production. Th cells are the preferential targets of human retroviruses. Infections with human T-cell leukemia virus (HTLV) or human immunodeficiency virus (HIV) result in the expansion of Th cells by the action of HTLV (adult T-cell leukemia) or the progressive loss of T cells by the action of HIV (AIDS). Both retrovirus infections impart a high-level activation state in the host immune cells as well as systemically. However, diverging responses to this activation state have contrasting effects on the Th-cell population. In HIV infection, Th-cell loss has been attributed to several mechanisms, including a selective elimination of cells by apoptosis. The induction of apoptosis in HIV infection is complex, with many different pathways able to induce cell death. In contrast, infection of Th cells with HTLV-1 affords the cell a protective advantage against apoptosis. This advantage may allow the cell to escape immune surveillance, providing the opportunity for the development of Th-cell cancer. In this review, we will discuss the impact of Th-cell activation and general immune activation on human retrovirus expression with a focus upon Th-cell function and the progression to disease. PMID:8987361

  7. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  8. American coal imports 2015

    SciTech Connect

    Frank Kolojeski

    2007-09-15

    As 2007 ends, the US coal industry passes two major milestones - the ending of the Synfuel tax break, affecting over 100M st annually, and the imposition of tighter and much more expensive safety measures, particularly in deep mines. Both of these issues, arriving at a time of wretched steam coal price levels, promise to result in a major shake up in the Central Appalachian mining sector. The report utilizes a microeconomic regional approach to determine whether either of these two schools of thought have any validity. Transport, infrastructure, competing fuels and regional issues are examined in detail and this forecasts estimates coal demand and imports on a region by region basis for the years 2010 and 2015. Some of the major highlights of the forecast are: Import growth will be driven by steam coal demand in the eastern and southern US; Transport will continue to be the key driver - we believe that inland rail rates will deter imports from being railed far inland and that the great majority of imports will be delivered directly by vessel, barge or truck to end users; Colombian coal will be the overwhelmingly dominant supply source and possesses a costs structure to enable it to compete with US-produced coal in any market conditions; Most of the growth will come from existing power plants - increasing capacity utilization at existing import facilities and other plants making investments to add imports to the supply portfolio - the growth is not dependent upon a lot of new coal fired capacity being built. Contents of the report are: Key US market dynamics; International supply dynamics; Structure of the US coal import market; and Geographic analysis.

  9. Mercury and silver induce B cell activation and anti-nucleolar autoantibody production in outbred mouse stocks: are environmental factors more important than the susceptibility genes in connection with autoimmunity?

    PubMed

    Abedi-Valugerdi, M

    2009-01-01

    Environmental and predisposing genetic factors are known to play a crucial role in the development of systemic autoimmune diseases. With respect to the role of environmental factors, it is not known how and to what extent they contribute to the initiation and exacerbation of systemic autoimmunity. In the present study, I considered this issue and asked if environmental factors can induce autoimmunity in the absence of specific susceptible genes. The development of genetically controlled mercury- and silver-induced B cell activation and anti-nucleolar autoantibodies (ANolA) production in genetically heterozygous outbred Institute of Cancer Research (ICR), Naval Medical Research Institute (NMRI) and Black Swiss mouse stocks were analysed. Four weeks of treatment with both mercury and silver induced a strong B cell activation characterized by increased numbers of splenic antibody-secreting cells of at least one or more immunoglobulin (Ig) isotype(s) in all treated stocks. The three stocks also exhibited a marked increase in the serum IgE levels in response to mercury, but not silver. More importantly, in response to mercury a large numbers of ICR (88%), NMRI (96%) and Black Swiss (100%) mice produced different levels of IgG1 and IgG2a ANolA (a characteristic which is linked strictly to the H-2 genes). Similarly, but at lower magnitudes, treatment with silver also induced the production of IgG1 and IgG2a ANolA in 60% of ICR, 75% of NMRI and 100% of Black Swiss mice. Thus, the findings of this study suggest that long-term exposure to certain environmental factors can activate the immune system to produce autoimmunity per se, without requiring specific susceptible genes.